Review

A natural solution for obesity: Bioactives

for the prevention and treatment of
weight gain. A review
Cristina Torres-Fuentes1, Harriët Schellekens 1, Timothy G. Dinan 1,2,3,
John F. Cryan 1,3,4
1
Food for Health Ireland, University College Cork, Cork, Ireland, 2Department of Psychiatry, University College
Cork, Cork, Ireland, 3Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, University College
Cork, Cork, Ireland, 4Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland

Objectives: Obesity and obesity-related disorders are reaching epidemic proportions worldwide. In this
review, we summarize the accumulating studies that have emerged in the last few decades demonstrating
that bioactives from different natural sources could potentially have anti-obesity effects.
Methods: We carried out an extensive search of relevant literature from Pubmed, Web of Knowledge, and
other online databases for studies where anti-obesity effects were shown by compounds from natural
sources.
Results: Appetite suppression, lipid metabolism regulation, and increase of energy expenditure are the main
mechanisms by which anti-obesity effects are exerted. Plants represent the most studied natural source of
anti-obesity bioactives. Camellia sinensis is the most representative species exerting several anti-obesity
effects. Moreover, probiotics (bacteria which bestow health benefit), such as strains of Bifidobacteria and
Lactobacillus families, and certain prebiotics (non-viable food components that confers a health benefit on
the host associated with modulation of the microbiota effects), such as insulin-type fructans, have also
shown capability to combat obesity. Finally, compounds from animal sources, in particular bioactive
peptides derived from milk-derived whey and casein protein digestion, high dietary calcium, and omega-
3s polyunsaturated fatty acids (n-3 PUFA) present in fish oils, have also shown potential anti-obesity effects.
Discussion: Several anti-obesity effects have been observed in different natural bioactives providing an
interesting and potentially safer and more desirable treatment strategy for the development of anti-obesity
functional or medical foods.
Keywords: Obesity, Natural bioactives, Food intake, Appetite

Introduction children, constituting one of the main health problems

Obesity and being overweight are defined by the
World Health Organization (WHO) as ‘abnormal or
excessive fat accumulation that may impair health’.1
The main cause is an imbalance between energy
intake and energy expenditure resulting from environ-
mental factors such as unhealthy diets, physical inac-
tivity, or smoking.2 However, genetic predisposition
may also contribute to the development of obesity
within susceptible individuals.3–5 Indeed, 40–70% of
the population variation in body mass index (BMI)
is due to genetic factors.6,7
During the last decade, the prevalence of obesity and
being overweight is increasing in both, adults and
Correspondence to: John F. Cryan, Department of Anatomy and
Neuroscience, University College Cork, College Rd., Cork, Ireland.
Email: j.cryan@ucc.ie
in the Western world. Thus, WHO global estimations
from 2008 showed that more than 1.4 billion adults were
overweight (BMI ≥ 25 kg/m2) and 500 million of them
were clinically obese (BMI ≥ 30 kg/m2)1. In addition,
obesity increases the risk of various obesity-related dis-
eases such as stroke, osteoarthritis, sleep apnea, some
cancers, inflammation-bases pathologies, and other path-
ologies belonging to the metabolic syndrome.8
Current strategies targeting obesity are either to (1)
decrease appetite through action on the central
nervous system, (2) modulate metabolism through per-
ipheral actions, (3) alter fat absorption, and (4) modu-
late gut peptide receptors.9–11 In the last years, several
molecules have been developed for the treatment of
obesity (Table 1).12–15 Phentermine was the first appe-
tite suppressant approved by FDA in 1959. It is a

© W. S. Maney & Son Ltd 2015

DOI 10.1179/1476830513Y.0000000099 Nutritional Neuroscience 2015 VOL. 18 NO. 2 49
50

Torres-Fuentes et al.
Nutritional Neuroscience

Natural solution for obesity

Table 1 Therapeutics for obesity treatment

Generic name Mechanism Actual status Trade names®

2015

Phentermine Amphetamine analog stimulant → increase in central nervous system dopamine, Approved by FDA from 1959 Adipex-P; Anoxine-AM; Fastin;
norepinephrine and serotonin activity → decrease appetite Rejected by EMA from 2010 Ionamin; Obephen; Obermine;
VOL.

Obestin-30; Phentrol
Sibutramine Norepinephrine and serotonin reuptake inhibitor → decrease appetite Withdrawn from the market by EMA’s Committee from —
18

2010 due to cardiovascular concern

Orlistat or Gastrointestinal lipase inhibitor → decrease fat absorption Approved by FDA from 1999 Xenical®, Alli
NO.

Tetrahydrolipstatin
2

lorcaserin 5-HT2C receptor agonist → decreases appetite Approved by FDA from 2012 Belviq®
Rimonabant Cannabinoid receptor antagonist → decrease appetite Withdrawn from the market by FDA and EMA from 2007 —
and 2008, respectively, due to an increased risk of
depression, anxiety and suicidal ideation
Metformin Decrease hepatic glucose output, increases insulin-mediated glucose utilization Approved by FDA from 1994 Glucophage
in peripheral tissues and reduce substrate availability for
gluconeogenesis → reduce weight in people with Diabetes mellitus 2
Exenatide Analogue of GLP-1 which is secreted in the intestine in response to Approved by FDA from 2005 Byetta
food → Increase insulin secretion, suppresses pancreatic release of glucagon,
helps slow down gastric emptying, reduce appetite, promote satiety via
hypothalamic receptors
Liraglutide Approved by EMA from 2006
Approved by FDA from 2010 Victoza
Approved by EMA from 2009
Pramlintide Synthetic analogue of amylin which is secreted in the pancreas after Approved by FDA from 2005 Symlin
feeding → delay gastric emptying and promote satiety
Topiramate Fructose monosaccharide derivative with sulphamate functionality → increases Approved by FDA from 1996 Topamax
energy expenditure, decreases energetic efficiency, and decreases caloric Rejected by EMA from 2012 due to increased risk of
intake cardiovascular events such as myocardial infarction or
stroke

FDA, Food and Drug Administration; EMA, European Medicines Agency.

Modified from the study of Derosa and Maffioli13 and Schellekens et al. 245.
 Table 2 Central and peripheral peptides and hormones involved in food intake and energy expenditure signalling pathways

Effect on the
Hormone/peptide Production site feeding Mechanism

Neuropeptide Y (NPY) Npy/AgRP/GABA neurons in the ARC of hypothalamus and dorsovagal Orexigenic Bind to seven-trasnmembrane-domain G-protein-coupled Y1–6 receptors in the
complex of the medulla hypothalamus → stimulation of orexigenic neurons and inhibition of POMC/
CART and other anorexigenic neurons
Agouti-related peptide Npy/AgRP/GABA neurons in the ARC of hypothalamus Orexigenic Melanocortin receptors inhibitor (MC3R and MC4R) → inhibition of anorexigenic
(AgRP) neurons in the paraventricular nucleus (PVN)
Melanocyte-stimulating POMC/CART neurons (hypothalamus) Anorexigenic Melanocortin receptor agonist (MC3R and MC4R) → stimulation of anorexigenic
hormone (α-MSH) neurons in the paraventricular nucleus (PVN)
Orexins (also called Lateral hypothalamic area (LHA) Orexigenic Bind to seven-trasnmembrane-domain G-protein-coupled OX1-Rs and OX2-Rs
hypocretin) receptors in the hypothalamus (ventromedial nucleus (VMH) and
PVN mainly) → increase the secretion of adrenocorticotropin-releasing
hormone (CRH) and arginine-vasopressin (AVP)
Insulin Pancreas Anorexigenic Bind to insulin receptors (INSR) in the ARC → inhibits the release of NPY/AgRP
and stimulates α-MSH and CART secretion
Leptin Adipose tissue; stomach; placenta; skeletal muscle and mammary Anorexigenic Bind to leptin receptors (LepR) in the ARC → inhibits the expression of
epithelium orexigenic NPY/AgRP hypothalamic neurons and stimulates the anorexigenic
POMC neurons in ARC
Peptide YY3-36 (PYY) Enteroendocrine L-cells of the distal gut Anorexigenic Bind to Y1, Y2, Y3 and Y5 receptors → decrease appetite and cause weight loss
by inhibiting ARC expressions of NPY/AgRP
Ghrelin Both derived of the preproghrelin secreted in the stomach (X/A-like cells Orexigenic Bind to ghrelin receptor (GHSR) in the ARC of the hypothalamus → stimulation of
of enteroendocrine cellular system) mainly; also in specific neurons of NPY/AgRP orexigenic neurons and inhibition of POMC/CART anorexigenic
the hypothalamus; human umbilicial vein endothelial cells; neurons
chondrocytes; cardiomyocytes; T cells; others tissues
Nutritional Neuroscience

Obestatin Anorexigenic Bind to orphan G-protein coupled receptor (GPCR) in liver, gastrointestinal tract,
adipose tissue and pancreas → increase insulin secretion and suppressed
both food intake and gastric emptying activity
Cholecystokinin (CCK) Duodeno-jejunal endocrine L-cells; cells in peripheral nerves; neurons of Anorexigenic Bind to CCK receptors on vagal afferent nerves → short-term inhibition of food
the brain intake by cooperation with the signals originating from the mechanoreceptors

Torres-Fuentes et al.
of the gut that are generated by the distention of the gut and transmitted to
brain through vagal afferents
Glucagon-like peptides Enteroendocrine L-cells of the distal gut; pancreas; CNS Anaroxigenic Bind to GLP receptors (GLPR) on vagal nerves → reduce the postprandial
GLP-1 and GLP-2 demand of insulin to maintain euglycemia after a meal and delay gastric
emptying
Oxyntomodulin (OXM) Enteroendocrine L-cells of the distal gut; CNS Anorexigenic Short-term inhibition of food intake thought activation of GLP-1 receptor,
2015

reduction of plasma ghrelin levels and stimulating hypothalamic release of

anorexigenic peptides

Natural solution for obesity

Serotonin (5HT) Enterochromaffin cells and in both enteric and central system Anorexigenic Bind to 5HTx receptors (in particular 5HT1B, 5HT2C and 5HT6 receptors)
VOL.

CNS, central nervous system.

18
NO.
2
51
Torres-Fuentes et al. Natural solution for obesity
sympathomimetic amine that is available in most
countries for short-term use, but long-term clinical
trials showed increased tolerance and dependency.16
On the other hand, the synthetic analogue of lipstatin,
also known by its generic name orlistat (Xenical®
Roche Products (Ireland) Ltd.; FDA approved 1999)
is the most commonly used clinical treatment for
obesity. It is a potent inhibitor of gastrointestinal,
gastric, pancreatic, and carboxylester lipase.17,18
Thus, this drug is able to compete with dietary fats
for sites on the lipase molecules and has been shown
to block the intestinal absorption of about 30% of
dietary fat at a therapeutic oral dose of 120 mg three
times a day. In addition, orlistat inhibits the hydrolysis
of dietary triglycerides decreasing intestinal absorp-
tion of the monoglycerides and free fatty acids pro-
duced during the lipolysis process.19 Orlistat has also
positive effects on diabetic control and has a generally
good safety profile on cardiovascular events. However,
it has also exhibited gastrointestinal side effects such as
oily stools, oily spotting, and flatulence among
others.20 Afterward, Arena Pharmaceuticals devel-
oped lorcaserin (Belviq®; FDA approved 2012), a
potent and selective agonist of 5-HT2C receptor
leading to decreased appetite.21 Hence, lorcaserin
became the first weight-loss drug since 1999.
Nevertheless, lorcaserin has been also associated
with different side effects such as headache, dizziness,
and nausea.22 Furthermore, many anti-obesity thera-
pies, including the monoamine reuptake inhibitor
sibutramine and cannabinoid receptor antagonist
rimonabant, have been withdrawn from the market
because of their adverse effects such as tolerance,
dependence, psychiatric problems, depression, and
even suicide13 (Table 1). Hence, the current pharmaco-
logical anti-obesity treatment options remain limited
due to poor efficacy and side effects.12,13,23,24
Therefore, there is an urgent need to find natural
bioactives for the prevention or treatment of obesity
which may replace some of these therapeutics which
are associated with adverse effects.
Understanding the pathways implicated in appetite
modulation is crucial for the development of effective
treatments. Table 2 shows the main central and periph-
eral peptides and hormones that are involved in food
intake and energy expenditure signalling pathways.
These different receptors are possible targets in the
prevention or treatment of obesity. Thus, one of the
main aims in this field of bioactive mining is the identi-
fication of natural bioactives able to modulate the
receptors implicated in these signalling pathways.
In this review, we examine the current state of the art
in the context of exploiting natural products for bioac-
tives that have shown anti-obesity effects. To this end,
we performed an extensive literature search from
Pubmed, Web of Knowledge, Google Scholar, and
52 Nutritional Neuroscience 2015 VOL. 18 NO. 2
other online databases for relevant studies where com-
pounds from natural sources have shown anti-obesity
effects. These natural bioactives may have potential
as effective alternatives to the currents anti-obesity
therapeutic constituting a safer and more desirable
treatment strategy for obese patients.
Natural bioactives in the prevention and/or
treatment of obesity
‘Natural bioactive substances’ have been defined as
‘natural compounds that can affect biological pro-
cesses or substrates and, hence, have an impact on
body function or condition and ultimately health’.25
Many of these bioactive compounds with different
beneficial activities in different body systems have
been discovered from animal and plant sources.
These compounds vary in chemical structure and func-
tion and include vitamins, specific bioactive proteins
or peptides, oligosaccharides, fatty acids, and phenolic
compounds. These bioactives have shown biological
functionalities such as antioxidant, anti-inflammatory,
anticancer, hypocholesterolemic, antimicrobial,
antithrombotic, chelating, opioid, immunomodula-
tory, satiety modulators, anticoagulant, or antihyper-
tensive effects.17,26–30 In addition, these natural
substances appear safer for the patient since they
occur mainly in foods, and therefore are more accepta-
ble as treatment compared with synthetic therapeutics.
In recent years, the potential of natural products for
obesity has increasingly become of considerable interest
to the food industry.31 Several natural bioactives with
different activities useful in the prevention of obesity or
obesity-related diseases, such as inhibitors of enzymes
implicated in digestion and absorption of dietary fat,
inhibitors of adipogenesis and adipogenic factors and
appetite suppressants, have been described.2,17,32 The
further development of such natural bioactives may
potentially lead to novel strategies to maintain a
healthy weight and to combat the obesity epidemic. In
addition, the combination of several of these natural
bioactives may results in synergistic effects leading to
an improved bioavailability profile. Moreover, the simul-
taneous modulation of multiple different molecular
targets in a dual bioactive approach is an advantage
with respect to drugs specific for a single target and
may result in higher efficacies with a lower dose of each
individual bioactive administrated.33
Anti-obesity bioactives from plants
Vegetables and fruits are considered a good source of
bioactive compounds including dietary fibre and
organic micronutrients such as carotenoids, polyphe-
nols, tocopherols, vitamin C, and others.34 Thus,
400 g of fruits and vegetables (excluding potatoes
and other starchy tubers) is the minimum daily
requirement recommended for the prevention of

chronic diseases such as heart disease, cancer, diabetes,
and obesity, as well as for the prevention of several
micronutrient deficiencies.35 In addition, plants are
becoming of interest as a source for the purification
of bioactive compounds due to their abundance and
low cost. Accordingly, more than three thousand
peer-review papers about bioactive compounds from
plant products have been published in the last five
years. However, there is a lack in research of the
quality, efficacy and safety of these products.
Although plants may be safer with potentially less
side effects than synthetic drugs, many also contain
potentially toxic compounds such as pyrrolizidinic
alkaloids, aristolochic acid, berberine, or curcubitacins
(for review, see Ref.36). Actually, some clinical trials
have shown side effects, such as allergy, gastrointesti-
nal tract disturbance, headache, or increased central
nervous system depression, in patients taking plant-
derived medicinal products (for review, see
Refs.37–39). Therefore, there is a clear necessity for
further investigation regarding the safety of plants-
derived medicinal products. Plant-derived products,
particularly medicinal plants, are believed to possess
potential anti-obesity agents that can act through
various mechanisms promoting weight maintenance
benefits.17 Indeed, there are several studies describing
plant metabolites with anti-obesity effects.17,31,32,40,41
In total, 50 different plants have been reported from
which anti-obesity compounds have been isolated.41
The main mechanisms of these plant-derived anti-
obesity bioactives are discussed below and include
(1) regulation of lipid metabolism, (2) suppression of
food intake and (3) stimulation of energy expenditure.
Regulation of lipid metabolism
Lipolysis stimulation effects
Adipose tissue lipolysis is a catabolic process in which
triglycerides stored in adipocytes are hydrolyzed and
released as fatty acids and glycerol into the plasma.
Decreasing fat storage by stimulating this lipolysis
process may contribute to combat obesity. The
hydrolysis of triglycerides is regulated by catechol-
amines such as noradrenaline and adrenaline via
β-adrenoceptors and antilipolytic α-2-adrenoceptors.42
Several studies have shown different plant extracts to
be able to stimulate this lipolysis process. Thus,
Nelumbo nucifera extracts were found to up-regulate
lipid metabolism in mice and rat models.43 N. nucifera
extracts caused a concentration-dependent significant
increase in glycerol release in 3T3-L1 adipocytes.
This effect was attributed to the N. nucifera extracts
stimulation of the β-adrenoceptors in white adipo-
cytes, which increase the lipolytic response.43 A
similar study demonstrated that dietary supplemen-
tation of N. nucifera extracts resulted in significant
suppression of body weight gain in A/J mice fed a
Torres-Fuentes et al. Natural solution for obesity
high fat diet through β-adrenoceptors activation by
flavonoids present in this extract.44 Cyperus rotundus
tubers extract have also shown this effect in Zucker
rats, inducing a significant reduction in weight gain
without affecting food consumption.45 In vitro, this
extract was able to stimulate lipolysis in 3T3-F442 adi-
pocytes, suggesting that this medicinal plant contains
activators of β-adrenoreceptors.45 Moreover, an iso-
propyl derivative, isopropyl-norsynephrine, found in
Citrus aurantium extracts has shown lipolytic action
in human adipocytes.46
In addition, excessive increases in circulating fatty acid
levels significantly contribute to the development of
obesity-related diseases such as dyslipidemia.42
Therefore, the inhibition of fatty acid release may also
be of therapeutic interest. The ethanol-based extract of
Euonymus alatus has shown anti-hyperlipidemia activity
in high-fat diet-induced hyperlipidemic mice through
increased mRNA expression of peroxisome prolifera-
tor-activated receptor γ (PPARγ) in the periepididymal
fat pad.47 PPARγ is a transcription factor mainly
expressed in adipose tissue which regulates lipid metab-
olism and energy balance through the expression of
genes encoding fatty acid-oxidizing enzymes.48. PPARγ
decreases triglycerides and fatty acid levels and supresses
TNF-α gene expression, which is a mediator of insuline
resistence.47,49 Furthermore, a mixture of herbal extracts
from Morus alba, Melissa officinalis, and Artemisia capil-
laris, has shown decreased circulating levels of triglycer-
ides and total cholesterol, and inhibited lipid
accumulation in high-fat diet-induced obese mice by
increasing hepatic mRNA levels of PPARα.48 The
aqueous extract of Salacia oblonga root has also shown
the capability to decrease fatty acid release via increased
expression of PPARα in Zucker diabetic fatty rats.50,51
Moreover, one of the most abundant dietary flavonoids,
quercetin, found in several foods such as fruits, onions,
teas, and garlic is known to decrease the TNF-α-
mediated suppression of PPARγ activity and PPARγ
target genes in primary adipocyetes.52
Finally, AMP-activated protein kinase (AMPK) is
an enzyme whose activation has been suggested to
mimic or potentiate exercise-related effects, such as
fatty acid oxidation.53 AMPK activation inhibits adi-
pocyte differentiation and suppresses the expression
of lipogenic molecules, such as fatty acid synthase,
acetyl-CoA carboxylase, and PPARγ.54 Hence, activa-
tors of this enzyme are a potential therapeutic target
for the treatment of obesity and obesity-related dis-
eases such as metabolic syndrome and type-2 diabetes.
An extract of Myristica fragans has shown activation
of AMPK in myoblast differentiated C2C12 cells.55
Extracts of Juniperus chinensis,56 Ginseng leaf,57 and
Camellia sinensis 58 have been reported to active
AMPK in obese rats and mice, and human cell
models, respectively.
Nutritional Neuroscience 2015 VOL. 18 NO. 2 53
Torres-Fuentes et al. Natural solution for obesity
Lipase inhibitory effects
Lipase inhibitory activity is one of the anti-obesity
mechanisms most widely studied in the research of
natural products against obesity.20,59 Lipases are
enzymes implicated in the digestion, transport, and
processing of dietary lipids. Pancreatic lipase is one
of the lipases most studied since it is the most impor-
tant enzyme responsible for the hydrolysis of triglycer-
ides into mono- and diglycerides and into smaller fatty
acids to be absorbed by the body.60,61 Different pan-
creatic lipase inhibitors from natural sources including
phytochemicals such as saponins, polyphenols, or ter-
penes, have shown capacity to inhibit pancreatic
lipase.17,20 Saponins constitute the largest group of
phytochemicals with this capability. Thus, saponins-
rich fractions from different plants such as
Platycodin grandiflorum, Scabiosa thchiliensis,
Accanthopanax sessiliflorus, Panax japonicas,
Aesculus hippocastanum, or Cyclocarea paliurus have
shown pancreatic lipase inhibitory activity (for
review, see Ref.20). On the other hand, polyphenols
also exhibit inhibitory activity for enzymes due to
their ability to join proteins through hydrophobic
and hydrogen bounds causing protein aggrega-
tion.20,59,62 Polyphenol-rich extracts from different
kinds of plants such as N. nucifera, Salacia reticulata,
Arachis hypogaea ( peanut) shell extract, Cassia
nomame, or C. sinensis (tea) have also been identified
to inhibit pancreatic lipase (for review, see Ref.20).
Synergistic action of several compounds within the
extracts such as flavonoids and procyanidins as well
as their antioxidative metabolites, may contribute to
the pancreatic lipase inhibitory effect. In addition,
some terpenes such as carnosic acid and the caroten-
oids crocin and crocetin have exhibited pancreatic
lipase inhibition, and in the case of crocin and crocetin
also hypotriglyceridemic, hipocholesterolemic, and
hypolipidemic activities (for review, see Ref.20).
Furthermore, inhibition of the lipoprotein lipase has
also been targeted as an anti-obesity strategy, due to
the fact that this enzyme catalyses the hydrolysis of
blood triglycerides releasing free fatty acids and
leading to an increased storage of triglycerides in
adipose tissue.17,63 Extracts from S. reticulata and
from tropical plants such as Morinda citrifolia or
Centenella asiatica have shown lipoprotein lipase
inhibitory activity.59,64,65
Inhibition of adipogenesis
Plants with adipogenesis inhibitory effects have also
been described.66,67 Adipocytes are the main cellular
component of adipose tissue, in which excess energy
is stored as triglycerides and thus constitute the main
energy reserve in animals including humans.68
Obesity is characterized by adipocytes hyperplasia
and hypertrophy.69 Thus, inhibition of adipocyte
54 Nutritional Neuroscience 2015 VOL. 18 NO.
proliferation and differentiation may promote weight
loss and restore the energy balance in obesity. C. sinensis
(green tea) is the most studied plant implicated in weight
loss.70 Green tea contains catechins, belonging to the
family of flavonoids, which have been suggested to be
responsible for this anti-obesity effect. In particular,
tea catechins inhibit the proliferation and differentiation
in the primary human visceral preadipocytes, and stimu-
lates the hepatic lipid metabolism.71–75
Epigallocatechin-3-gallate (EGCG), the most abundant
catechin in this plant, has shown inhibitory effects on
adipogenesis through downregulation of the gene
expression of the insulin resistance-related adipokine
resistin in 3T3-L1 adipocytes via extracellular signal-
related kinase (ERK) pathway.76 However, some
studies have shown that in the absence of caffeine,
other major component in tea, catechins did not show
significant anti-obesity effects.77 Also, extracts of
Solanum tuberosum, Vitis vinefera (grape), Momordica
charantia, Centella asiatica, and M. citrifolia have
shown inhibition of preadipocyte proliferation in a
dose-dependent manner and, in the case of M. charantia
and C. asiatica there was also inhibition of preadipocyte
differentiation in a time- and dose-dependent manner.
This inhibitory activity has been attributed to synergistic
effects of several flavonoids present in these
extracts.65,78–81 In addition, resveratrol, a polyphenol
compound with anti-obesity effects which is found in
wine, grapes, peanuts, and several berries, has been
reported to reduce lipogenesis via reduction of resistin
and other insulin resistance-related adipokines such as
retinol-binding protein 4 (RBP4) as well as to enhance
fatty acid oxidation capacity.82 Moreover, bioactive
non-flavonoids have been shown to inhibit adipogenic
proliferation.83 Thus, the most active component in
Curcuma longa (turmeric) preparations, known as curcu-
min, showed inhibition of adipogenesis in 3T3-L1 adi-
pocytes as well as inhibition of obesity in C57BL
mice.84 More recently, Llex paraguariensis (yerba
mate) extract has shown inhibition of adipogenesis in
vitro as well as in vivo in a high-fat diet-induced model
of obesity.85 It was attributed to regulation of the
expression of genes related to adipogenesis such as
down-regulation of Creb-1 and C/EBPα and up-regu-
lation of Dlk1, Gata2, Gata3, Klf2, Lrp5, Pparγ2,
Sfrp1, Tcf7l2, Wnt10b, and Wnt3a.85
Suppression of food intake
Plants with the capability to suppress food intake have
been also described (for review, see Ref.32). Appetite
suppressing plant-derived compounds directly affect
the central nervous system pathways implicated in
appetite and satiety regulation. Hoodia gordonii is
one of the plants most investigated as a natural
source of bioactives with appetite suppressant effects
(for review, see Ref.86). More than 20 international
2

patents on compounds originating in this plant and
many hoodia-containing commercial preparations
with appetite suppressant effects are currently avail-
able on the market.86 A group of steroidal glycosides,
developed by the pharmaceutical company
Phytopharm and referred to collectively as P57, are
responsible for this activity.87 In animal studies,
central nervous system injection of P57 showed a
40–60% decreased food intake over 24 hours.88 Also,
human trials carried out by Phytopharm showed a
reduction in the average daily caloric intake and in
the body fat content in the P57-treated group com-
pared with the placebo group.89 The mechanism of
these steroidal glycosides may be similar to the effect
of glucose on the brain cells, increasing hypothalamic
malonyl-CoA, decreasing orexigenic neuropeptide
expression, and suppressing food intake.90
Another potential natural appetite suppressant is the
commercially available Super CitriMaxR (HCA-SX),
supplied by InterHealth Nutraceuticals, Benicia, CA,
which is a calcium/potassium salt of (–)-hydroxycitric
acid extracted from the dried fruit rind of the plant
Garcinia cambogia.91 This compound has shown a
reduction in body weight gain in growing obese Zucker
rats92. Zucker rats are characterized by hypercholestero-
lemia, hyperlipidemia, hyperinsulinemia, insulin resist-
ance, increased oxidative stress, and inflammation and
have been used extensively as a model of early-onset
obesity.93–95 The possible mechanism whereby HCA-
SX reduces body weight gain may be due to its action
as a potent and specific inhibitor of ATP-citrate lyase,
an enzyme needed for the synthesis of fatty acids.96 The
extract of Cissus quadrangularis (trade name: CQR-
300, supplied by Gateway Health Alliances, Inc,
Fairfield, California, USA) is another natural appetite
suppressant currently available on the market.91,97 This
extract showed capability to decrease weight, blood
glucose levels, and serum lipids. Although its mechanism
of action is still unknown, it was hypothesized that it
increases serotonin (5-HT) levels.97
In addition, Catha edulis has also been reported to
decrease appetite via its main active ingredient, cathi-
none, which is a compound similar to amphet-
amines.98 Although its precise mechanism remains
unknown, it is believed to act in a similar way to sym-
pathomimetic substances on appetite via modification
of the hepatic metabolism.98–100
Moreover, other plant extracts and herbal
supplements such as C. sinensis have also been
suggested to contribute to appetite suppression via
decreased expression of neuropeptide Y and enhanced
serotonin (5-HT) release.101 Furthermore, adminis-
tration of green tea catechins via intraperitoneal injec-
tion have shown a significant reduced food intake in
adult Sprague Dawley lean and obese male Zucker
rats.102 In addition, Phaseolus vulgaris suppresses
Torres-Fuentes et al. Natural solution for obesity
appetite via phytohemoagglutinin-induced modu-
lation of the activity of cholecystokinin and gluca-
gon-like peptides.103 Finally, Caralluma fimbriata as
well as species belonging to Leguminoseae family
(legumes) possess appetite-suppressive effects via a
yet unknown mechanism.104,105
Stimulation of energy expenditure
Positive energy balance resulting from an increase in
food intake, reduced energy expenditure, and dysfunc-
tion of adipose biology is associated with the develop-
ment of obesity.106 Therefore, stimulation of energy
expenditure can also contribute to decrease the
obesity risk. Currently, there is no approved thera-
peutic targeting the stimulation of energy expenditure
available and the use of herbal medicines has become a
preferred alternative.106
Modulation of uncoupled protein 1 (UCP1) gene
expression is one of the main strategies to promote
energy expenditure.107 UCP1 is a mitochondrial trans-
porter present in the brown adipose tissue of rodents,
hibernators, and new-borns, that plays an important
role in the dissipation of energy as heat.108 The caroten-
oid fucoxanthin from brown seaweed has shown anti-
obesity effects via UCP1 upregulation in white adipose
tissue.109,110 Moreover, resveratrol, a phenolic com-
pound present in Vitis vinifera (grape), has shown capa-
bility to increase basal energy expenditure and adaptive
thermogenesis in mice fed a high-fat diet through
increases in the expression of UCP1 and other mito-
chondrial proteins such as the sirtuin 3 (SIRT3) and
mitofusin 2 (MFN2).106,111 Extracts of Pinellia ternate
have also been shown to increase energy expenditure
via UCP1 upregulation.112 The protein UCP3, another
member of the uncoupled protein family, is expressed
in heart and skeletal muscle and is involved in fatty
acid metabolism as well as in the protection from cell
damage caused by reactive oxygen species.113 In
addition, UCP3 is also identified as a potential anti-
obesity agent since it is implicated in the thermogenesis
regulated by the thyroid hormone, β3-adrenergic ago-
nists, and leptin.114 Oral administration of ethanolic
extract of a potato variety, S. tuberosum, at the dose of
200 mg/kg for 4 weeks, was shown to produce UCP3
upregulation in adipose and liver tissue of rats fed a
high-fat diet.32,106,115
On the other hand, inhibition of diacylglycerol acyl-
transferase (DGAT), a microsomal enzyme important
in the metabolism of glycerolipids, may also contribute
to an increase in energy expenditure.116 Tanshinone
compounds isolated from Salvia miltiorrhize, crypto-
tanshinone and 15, 16-dihydrotanshinone, have been
reported as DGAT inhibitors.117
Ephedra sinica has also shown anti-obesity effects
trough increase in energy expenditure in obese
mice.118 Ephedrine is believed to be the major alkaloid
Nutritional Neuroscience 2015 VOL. 18 NO. 2 55
Torres-Fuentes et al. Natural solution for obesity
in E. sinica implicated in its thermogenic effects via
increase of norepinephrine and epinephrine release
from sympathetic neurons (for review, see Ref.119).
In addition, ephedrine effects may be potentiated by
caffeine (for review, see Ref.119). Nevertheless, some
authors have reported studies in obese patients with
no significant weight loss after treatment with
ephedrine.120,121
Green tea (C. sinensis), which has been extensively
discussed above, has also been proposed to increase
energy expenditure.122–124 This capability has been
attributed mainly to its most abundant catechin epi-
gallocatechin-3-gallate.125 Several studies in human
and rodent models of diet-induced obesity have
reported this EGCG-mediated stimulatory effect on
energy expenditure to occur via different mechanisms:
(1) increased thermogenesis,125–127 (2) increased fat
oxidation in liver and muscle,125,128,129 (3) increased
glucose uptake in muscle,130,131 (4) decreased lipid
content in liver,132 and (5) increased faecal lipid
excretion.132 On the other hand, moderate consump-
tion of EGCG in overweight/obese post-menopausal
women undergoing regular exercise has shown to
reduce abdominal fat by reducing heart rate and
plasma glucose concentrations.133 In addition, green
tea is also rich in caffeine, which has also shown stimu-
latory effects via sympathetic activation of the central
nervous system and stimulation of thermogenesis and
fat oxidation.74,77,122,124,134 Therefore, green tea
extracts and caffeine mixtures seem to have excellent
potential as anti-obesity agents.135
Capsaicin species (hot peppers), Piper nigrum (black
pepper) and Zingiber officinale (ginger) have also
shown anti-obesity effects through increasing thermo-
genesis by enhancing catecholamine secretion from the
adrenal medulla via activation central nervous system
(for review, see Ref.136), Furthermore, caffeine may
increase thermogenesis via different mechanisms such
as increasing concentration of cAMP and nor-epineph-
rine, stimulating adipocyte phosphodiesterase, and lipo-
lysis and stimulating substrate cycles such as Cori cycle
and FFA-triglyceride cycle (for review, see Ref.136).
On the other hand, mixed medicinal anti-obesity
plant preparations instead application of single medic-
inal plants have shown a greater weight gain
(for review, see Ref.137). However, mixed medicinal
plant preparations show different side effects and
therefore lower degree of safety than single medicinal
plants. This may be due to interactions between
diverse compounds present in different plants.
Anti-obesity bioactives from bacteria: probiotic and
prebiotic strategies in obesity
Foods with added live microorganisms exerting ben-
eficial healthy effects ( probiotics) are receiving
increased demand from consumers and therefore
56 Nutritional Neuroscience 2015 VOL. 18 NO.
increased scientific and commercial focus in recent
years. Accordingly, the world probiotic market was
estimated at $24.23 billion in 2011 and more than
500 probiotic products have been introduced in the
past decade.138
Probiotics have shown to play an important role in
immunological, digestive, and respiratory functions
and may help to prevent infectious disease in chil-
dren.139 Beneficial effects of probiotics have been
shown in disorders associated with the gastrointesti-
nal tract such as diarrhoeas, Helicobacter pylori infec-
tion, inflammatory diseases and bowel syndromes,
cancer, constipation as well as beneficial effects on
mucosal immunity, allergies, cardiovascular disease,
and urogenital tract disorders (for review, see
Ref.139–141). These probiotic-mediated beneficial
effects on human health are due to changes in the
gut microbiota via oral delivery of viable strains of
bacteria that are then integrated into the gut
system.142 Gut microbiota ferment nutrients and
secrete bioactive compounds inducing several
responses within the intestinal mucosa and control-
ling the gut’s barrier and endocrine functions.142
Moreover, gut microbes also affect the metabolism
of cells in others organs such as liver and adipose
tissue and can thereby modulate lipid and glucose
homeostasis.142
In addition, prebiotics are known to produce quali-
tative and selective changes in the composition of the
gut microbiota through fermentation by bacteria of
certain non-digestible carbohydrates, which may
have beneficial effects on the host’s health.143
Moreover, prebiotics can modulate host gene
expression and metabolism.144
Consequently, both prebiotics and probiotics may be
useful to prevent or treat obesity and obesity-related dis-
eases by specific modulation of gut microbiota.
Probiotics in obesity
Abnormal or pathological changes in gut microbiota
promote gut permeability, increase metabolic endotox-
emia and increase the risk to develop metabolic dis-
orders such as obesity.145 Individuals with type 2
diabetes mellitus and/or obesity often display a
chronic low grade inflammation in the gut combined
with an altered composition of the gut microbiota.142
Interestingly, the gut microbiota has the ability to
influence the production of immune-modulatory pro-
teins and peptides in the gut.146–149 The serum
amyloid A3 protein (SAA3) is one such protein and
the most abundant SAA isoform in both the adipose
tissue and the colon.150 Upregulated SAA3 expression
has been reported in the adipose tissue of mice fed a
high-fat diet contributing to the chronic inflammation
associated with insulin resistance in obesity.151 Mice
colonized with a normal gut microbiota from healthy
2

wild-type mice (conventionalized mice) showed an
increased SAA3 expression in the adipose tissue and
colon as compared with germ-free mice.150
Lipopolysaccharides and potentially other com-
ponents of the gut microbiota were proposed to
induce this elevated SAA3 expression via Toll-like
receptors-MyD88-NF-κB signalling pathway causing
chronic low-grade inflammation observed in
obesity.150 In addition, the healthy gut microbiota con-
tributes to normal gastrointestinal tract motility and
maintenance of barrier function.152 Furthermore,
altered microbiota may subsequently change the
uptake of nutrients and increases energy
harvest.153,154 Thus, conventionalization of adult
germ-free C57BL/6 mice with a normal microbiota
harvested from conventionally raised animals have
shown to increase the body fat content and insulin
resistance within 14 days despite reduced food
intake.155 In addition, microbiota transplantation
from mice with diet-induced obesity to lean germ-
free mice have also shown higher fat deposition than
transplants from lean donors.156 Healthy gut micro-
biota increases absorption of monosaccharides from
the gut lumen resulting in the induction of hepatic
lipogenesis.155 Moreover, the healthy microbiota
promotes storage of triglycerides in adipocytes by sup-
pression of the intestinal expression of the fasting-
induced adipocyte factor (Fiaf ) which is a circulating
lipoprotein lipase inhibitor.155 Furthermore, in con-
trast to mice with a normal microbiota, germ-free
animals are protected against a diet-induced obesity
via increased levels of Fiaf and elevated AMPK
activity, which results in increased fatty acid metab-
olism.157 Moreover, obesity has been related to
changes in the relative abundance of members from
Bacteroidetes and Firmicutes bacterial divisions.154,158
Thus, decreased population of Firmicutes and
increased population of Bacteriodetes shifted pro-
portionately to weight loss in obese individuals.158
Furthermore, lean gnotobiotic mice inoculated with
obese mice gut microbiota developed glycemia, insuli-
nemia, and fat stores within two weeks.153 Taken
together, modulation of the gut microbiota may be
promising nutritional and pharmacological target in
the management of obesity and obesity-related
disorders.142
Recently, several studies have highlighted the poten-
tial role of probiotics in the treatment of obesity (for
review, see Ref.159–161). In a study by the food
company Danisco, the probiotic strain
Bifidobacterium (B.) animalis subsp. lactis 420
(B420) has been reported to reduce tissue inflam-
mation and metabolic endotoxemia counteracting
the adverse effects of a high-fat diet in C57BL/6
mice.162 Moreover, Lactobacillus (L.) gasseri SBT
2055 (LG2055) significantly reduced the abdominal
Torres-Fuentes et al. Natural solution for obesity
adiposity, body weight, and inflammation trials in
rats fed a high-fat diet and adults with obese ten-
dencies suggesting its beneficial influence on metabolic
disorders.163,164 Furthermore, this strain also showed a
decreased cell size of visceral adipose tissue in
Sprague–Dawley rats.165 In a subsequent study,
Zucker rats fed with milk fermented with this strain
showed decreased adipocytes size, reduction in fat
mass, decreased plasma leptin levels, and increased
fatty acids in faecal content.166 In addition, the L.
gasseri BNR17 and the Bifidobacterium breve B3
strain prevented increases in body weight and
adipose tissue in diet-induced overweight rats and
mice, respectively.167,168 Moreover, the human-
derived Lactobacillus rhamnosus PL60, reduced body
weight without decreasing energy intake and caused
a significant, specific reduction of white adipose
tissue in obese mice.169,170 This anti-obesity effect
was due to the amount of conjugated linoleic acid
(CLA) produced by L. rhamnosus PL60. Recently,
the presence of A. mucininiphila has been shown to
improve metabolic profile and to reverse high-fat
diet-induced metabolic disorders such as fat-mass
gain, metabolic endotoxemia, adipose tissue inflam-
mation, and insulin resistance.171
Prebiotics in obesity
Interestingly, a high-fat diet has been shown to
promote the colonization by Gram-negative microbes
and to specifically cause a decrease in Bifidobacterium
spp.146 In addition, lipopolysacharide (LPS), produced
in the gut due to the death of these Gram-negative bac-
teria, results in metabolic endotoxemia, which is a
common characteristic in obese individuals.145 It has
been demonstrated that Bifidobacterium favours the
reduction of intestinal endotoxin formation and the
improvement of intestinal barrier function through
increased expression of tight junction proteins and
decreased circulating pro-inflammatory cyto-
kines.172–174 Interestingly, a lower number of
Bifidobacteria has indeed been observed in individuals
with obesity or type 2 diabetes compared with lean
individuals.173,175–177 Moreover, the number of
Bifidobacterium spp. was inversely correlated with fat
mass, glucose intolerance, and LPS level in high-fat
diet-induced diabetes mice.178 Therefore, the increase
of these bacteria in the gut may have potential for
the preventative measure or treatment of obesity. In
line with this hypothesis, is the observed increase in
the number of Bifidobacterium spp. in a genetic
mouse model of obesity and in mice with diet-
induced obesity, which were supplemented with
insulin-type fructans promoting their growth in the
gut.142,147,178,179 Moreover, these insulin-type fructans
have also been reported to increase the number of
endocrine L cells in the jejunum and in the colon of
Nutritional Neuroscience 2015 VOL. 18 NO. 2 57
Torres-Fuentes et al. Natural solution for obesity
rodents, leading to GLP-1 and GLP-2 release.180–183
GLP-1 is known to promote satiety and reduce food
intake in obese patients,184 and GLP-2 increases intes-
tinal cell proliferation and improves gut barrier func-
tions.147 Therefore, insulin-type fructans may
contribute to decreases in appetite, fat mass and
hepatic insulin resistance via increased GLP-1 levels,
and reduce permeability of the intestinal wall and
endotoxemia via increased GLP-2 levels.147,183 In
addition, insulin-type fructans were shown to decrease
the activity of the cannabinoid receptor 1 improving
adipogenesis and the barrier function of the gut.185
Finally, insulin-type fructans prebiotics demonstrated
decreases in the rate of adipocyte differentiation and
the adipocyte size via overexpression of G protein
coupled receptor 43 (GPR43), which is implicated in
the regulation of fatty-acid and glucose homeostasis
in adipose tissue and the intestines.179 Furthermore,
in a clinical study in obese patients, these non-digesti-
ble/fermentable carbohydrates were given as a sup-
plement for 3 months and showed decreased food
intake, body weight gain, and fat mass.186 These
patients also showed increased plasma of anorexigenic
peptide YY (PYY) levels following a meal, as well as
decreased ghrelin levels.186 In addition, in an other
clinical trial in healthy individuals, the administration
of inulin-type prebiotics (16 g/d for two weeks) also
showed increased plasma levels of gut peptides impli-
cated in appetite regulation such as GLP-1, PYY,
and gastric inhibitory polypeptide, causing a
decreased glycemic response and energy intake.187
Moreover, Faecalibacterium prausnitzii species have
been inversely correlated with diabetes and are directly
linked to the reduction of low-grade inflammation in
human obese subjects following Roux-en-Y Gastric
bypass surgery.188 Furthermore, Akkermansia mucini-
phila is inversely correlated with weight gain in preg-
nant women.189
Anti-obesity bioactives from animal sources
Although plants are the most common source of
natural bioactives due to their easy accessibility and
relatively cheap production cost, animal sources are
also increasingly becoming of interest. In particular
milk represents one of the most studied natural
sources of bioactives from animal origin. Growing evi-
dence suggests that consumption of low-fat milk and
dairy products, together with a high intake of fruits,
vegetables, and whole grains and a reduced intake of
meat, sugar, and fat, should have beneficial effects
on the prevention or treatment of obesity, cardiovascu-
lar disease, and type 2 diabetes.2,190 Vitamins, specific
proteins, oligosaccharides, fatty acids, and especially
bioactive peptides, have been the most studied
among all these dietary components (for review, see
Ref.191). At present, milk proteins are considered the
58 Nutritional Neuroscience 2015 VOL. 18 NO.
most important source of bioactive peptides.27,192
Peptides with beneficial effects in the obesity or
obesity-related diseases such as antihypertensive,193,194
anti-thrombotics,195 anti-cholesterolemics,196 antioxi-
datives,30,197 and food intake suppressors198,199 have
been reported. Dairy-derived peptides have also been
associated with satiety enhancing potential and may
be utilized for the development of anti-obesity bioac-
tives (for review, see Ref.2).
Whey protein constitutes about 20% of total milk
proteins200 and its gastrointestinal digestion leads to
generation of several bioactive peptides and amino
acids201,202 which stimulate several gut hormones
associated with the regulation of food intake, such as
cholecystokinin (CCK),199,203,204 PYY,205,206 and
ghrelin.204,207,208 In addition, whey protein has
shown an enhanced release of CCK and PYY and a
reduced ghrelin secretion, underlying a potential role
in hunger suppression via reduced food intake and
increased satiety.209 One of the mammalian milk-
derived whey proteins, lactoferrin, has recently been
reported to reduce abdominal obesity via the regu-
lation of lipopolysaccharide concentration and main-
tenance of an adequate lipid profile.210,211
Furthermore, chronic intake of lactoferrin has shown
to decrease visceral fat accumulation in humans.212
Another important milk-derived whey protein with
therapeutic potential against obesity and obesity-
related disorders is alpha-lactalbumin.213–215 Alpha-
lactalbumin has exhibited different anti-obesity
effects such as hunger suppression, increased energy
expenditure and protein balance, and decreased fat
balance.214 On the other hand, alpha-lactalbumin
has been shown to enhance serotonin release in rats
via a higher bioavailability of its precursor trypto-
phan216 which could be a potential mechanism to
exert its appetite suppressant effect. In addition, bio-
active peptides produced by α-Lac digestion have
been shown to decrease blood pressure, enhance
mineral absorption, affect gut microbiota, stimulate
immune function, regulate apoptotic cellular death
and inhibit angiotensin–I-converting enzyme.217–220
Furthermore, casein protein constitutes 80% of the
total protein fraction in milk.200 Peptides derived
from casein hydrolysis have shown satiety effects by
different mechanisms such as stimulation of CCK
release221 and GLP-1 release.198,199 Moreover,
casein-derived hydrolysates have been shown to stimu-
late the 5-HT2C serotonin receptor suggesting a poten-
tial appetite suppressing effect.222
Moreover, high dietary calcium (Ca2+) has been
reported to have anti-obesity and anti-inflammatory
properties and to reduce adiposity.223 However, the
mechanisms mediating the metabolic effects of Ca2+
remain to be elucidated. Formation of indigestible
Ca2+ soaps in the gastrointestinal tract, promoting
2
 Torres-Fuentes et al. Natural solution for obesity

an increased faecal fat loss, has been proposed as one
possible mechanism by which high dietary Ca2+
reduces adiposity.224
Although milk represents one of the most important
natural source with anti-obesity activity, it is impor-
tant to take into consideration other compounds
derived from animals, such as omega-3s polyunsatu-
rated fatty acids (n-3 PUFA) present in fish oils (for
review, see Ref.225). Anti-obesity effects such as sup-
pression of appetite, improvements in circulation,
enhanced fat oxidation and energy expenditure, and
reduced fat deposition have all been attributed to
dietary intake of (n-3) PUFAs.226–229 PUFA activity
is mainly due to changes in gene expression levels of
lipogenic enzymes in the liver, in particular a
decreased mRNA expression of fatty acid synthase
(FASN) and acetyl-CoA carboxylase alpha.230–233
Recently, it has been reported that (n-3) PUFA may
also be implicated in the intestinal lipid metabolism
regulation.234 However, there is still a need for long-
term studies to determine the relative anti-obesity
effects of (n-3) PUFA, such as eicosapentaenoic acid
and decosahexaenoic acid, since the majority of the
studies that have been carried out are of short dur-
ation. Furthermore, α-lipoic acid, present in many
animal-derived food products such as organ meats
from the heart, liver, and kidneys (and also in some
vegetables such as broccoli and spinach), has shown
anti-obesity effects through suppression of hypothala-
mic AMPK.235 In addition, several studies have shown
that dietary conjugated linoleic acid, found in some
meat and dairy products, reduces body fat in
mice.236–241 However, in a human study with over-
weight subjects, conjugated linoleic acid did not
show effects in body weight regain after 13 weeks inter-
vention compared with placebo.242
Bioactive peptides derived from marine organism
have also shown anti-obesity effects (for review, see
Ref.243). Hence, peptides derived from shrimp head
protein hydrolysates have displayed anti-obesity
effects in STC-1 cells through stimulation of the
peptide hormone cholecystokinin, which is associated
with satiety.244
Conclusion
In summary, it is clear that several natural compounds
exist which have been described to exert beneficial
effects against obesity. Plants are the most studied
natural source of bioactives with anti-obesity effects
mainly due to the easy accessibility and the relatively
low production costs. Different bioactive compounds
isolated from several plant extracts, predominantly
phenolic compounds such as flavonoids, have shown
potential anti-obesity effects. The main mechanisms
through which these plant-derived bioactives exert
their anti-obesity effects include lipase inhibitory
activity, inhibition of adipogenesis, suppression of
food intake, stimulation of energy expenditure and
regulation of lipid metabolism. In particular, C. sinen-
sis (green tea) is one of the most representative plants

Table 3 Some current anti-obesity functional foods and supplements available in the market

Natural component Effects Trade names/companies

Omega-3 polyunsaturated
fatty acids
Eicosapentaenoic acid Appetite suppressant CHOLEDUZTM, Nature’s Way Products, Inc.
Reduces inflammation
Docosahexaenoic acid Decreases cholesterol Omega-3 Super Krill, JamiesonTM
Decreases stored body fat Natural sources

Herbal extracts Sim-N-Trim capsules

Camellia sinensis Thinogenics™
Nelumbo nucifera Appetite suppressant Citrus aurantium formula, Volcanat HealthR
Citrus aurantium Increase energy expenditure Salacia oblongoa extract, Vitacost
Salacia oblongoa Decrease stored body fat Ayusearch Obesity Management Formula, Aom Formula tablets
Cyperus rotundus 24/7 Weight Loss, Julian Bakery
Vitis vinifera Hoodia gordonii diet complex, Good’n Natural
Hoodia gordonii Extra Slim, PerfectaTM
Centella asiatica Fat Burner, Jitter FreeTM
Salacia reticulata
Lactobacillus and Promotes weight loss OptiBac probiotic, OptiBac probiotic
Bifidobacterium strains Enhanced digestion and acids transit Somae Health Probiotics, Somae Health
Fructooligosaccharides Support immune system Probiotic Probiotique, JamiesonTM

Whey protein concentrate Appetite suppressant VolactiveTM, Volac International

Increase energy expenditure and Slimfast, HC4TM, Unilever
protein balance
Maintenance of an adequate lipid profile Proti’Smooth TM, Laboratories PYC
Emulgold; Ultranor, Kerry Ingredients
Custom formulations, Hilmar Ingredients

Nutritional Neuroscience 2015 VOL. 18 NO. 2 59

Torres-Fuentes et al. Natural solution for obesity
with promising potential to treat or prevent obesity,
activating several of these mechanisms simultaneously.
On the other hand, prebiotics and probiotics are also
becoming of interest as anti-obesity agents. Changes
in healthy gut microbiota promote gut permeability,
increase metabolic endotoxemia and the risk to
develop metabolic disorders such as obesity.
Therefore, prebiotics and probiotics that favour quali-
tative and selective changes in the composition of the
gut microbiota may promote beneficial anti-obesity
effects and be useful for the prevention or treatment
of this eating disorder. Strains of Bifidobacteria and
Lactobacillus families and insulin-type fructans are
the probiotics and prebiotics most studied, respect-
ively. Reduced intestinal endotoxin formation,
enhanced intestinal barrier function and decreased cir-
culating pro-inflammatory cytokines, are some of the
beneficial effects that have been reported. Finally,
animal sources such as milk-derived whey and casein
proteins, high dietary calcium, and long-chain
omega-3 polyunsaturated fatty acids present in fish
oils have also shown therapeutic potential against
obesity. Thus, the main anti-obesity effects shown in
these natural bioactives from animal sources are (1)
modulation of gut hormones secretion implicated in
appetite regulation, (2) hunger suppression, (3)
increase energy expenditure and protein balance, and
(4) decrease fat balance.
Therefore, these natural compounds constitute an
interesting alternative to current pharmacological
anti-obesity therapeutics, which are often associated
with unwanted side effects. Hence, their incorporation
into functional foods may have potential for the food
industry and they may be developed as ingredients in
functional foods and/or medical foods to maintain a
healthy weight. Table 3 shows some functional foods
and supplements currently available in the market
with beneficial properties to treat obesity and other
obesity-related symptoms. Further studies aimed at
the identification of novel bioactives from natural
resources with potential anti-obesity effects are
poised to contribute to the development of thera-
peutics and functional foods to be used in the preven-
tion and/or treatment of obesity.
Acknowledgements
This work did not receive specific funding from any
public, commercial or not-for-profit organization.
The authors’ responsibilities were as follows C.T.F.,
H.S., T.G.D. and J.F.C. wrote the manuscript.
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