Blackwell Publishing LtdOxford, UKOBRObesity Reviews1467-7881© 2007 Queen’s Printer and Controller of HMSO; published with permission; Journal

compilation © 2007 The

International Association for the Study of Obesity? 20078••4144Review ArticleAdipocyte biology P. Trayhurn

obesity reviews

Adipocyte biology

P. Trayhurn

Obesity Biology Unit, University of Liverpool, Keywords: Adipokines, inflammation, obesity, white adipose tissue
Liverpool, UK

Accepted 12 November 2006

Address for correspondence: Professor P

Trayhurn, Obesity Biology Unit, School of
Clinical Sciences, University of Liverpool, 3rd
Floor UCD Building, Liverpool L69 3GA, UK.
E-mail: p.trayhurn@liverpool.ac.uk

OnlineOpen: This article is available free online at www.blackwell-synergy.com obesity reviews (2007) 8 (Suppl. 1), 41–44

tissues – brown and white adipose tissue. Brown adipose

Background
Obesity is fundamentally a problem of energy balance –
irrespective of the underlying social, cultural, behavioural
and genetic determinants. As such, it can only develop
when energy (food) intake is in excess of total energy
expenditure (Basal Metabolic Rate, ‘thermogenesis’,
physical activity, ‘non-exercise activity thermogenesis’).
Differences between intake and expenditure are primarily
buffered by changes in the amount of lipid (triacylglycerols)
deposited in the specialized fuel storage organ, white adi-
pose tissue (or white fat). Until recently, research on energy
balance and obesity focused particularly on the central
neuroendocrine pathways involved in the hypothalamic
control of food intake and on the peripheral mechanisms
of adaptive energy expenditure. White adipose tissue,
however, attracted little research interest.
Adipose tissue has now moved centre stage in obesity
research, there having been a revolution in our understand-
ing of the biological role of the tissue over the past decade.
Indeed, adipose tissue biology is currently one of the ‘hot’
areas of biomedical science – principally because it is now
recognized as a major endocrine and signalling organ.
Characteristics of white adipose tissue
White adipose tissue is part of what Cinti has termed ‘the
adipose organ’, which consists of two functionally distinct
tissue is specialized for heat production by non-shivering
thermogenesis, and in this tissue the stored lipid droplets
serve primarily as a fuel for the production of heat. In white
adipose tissue, on the other hand, the stored triacylglycer-
ols provide a long-term fuel reserve for the animal. Indeed,
white fat is the main energy reservoir in mammals, triacyl-
glycerols providing fuel storage at a high energy density,
both because of the considerable caloric value of lipid
(39.1 kJ g−1 vs. 15.4–17.5 kJ g−1 for carbohydrate) and
because, in contrast to carbohydrates, triacylglycerols can
be stored with little associated water. The result is that up
to 85% of the weight of adipocytes consists of lipid.
In addition to fuel storage, white adipose tissue can act
as a thermal insulator and protect other organs from
mechanical damage. Two further features of the tissue
should be highlighted. First, unlike most other organs,
white fat is distributed in multiple depots in the body, both
subcutaneously and internally, and clusters of adipocytes
may also be located adjacent to, or embedded in, other
organs such as the lymph nodes and skeletal muscle. A
second important feature is that adipose tissue is not made
up simply of mature adipocytes, which store the lipid, but
contains a variety of other cells (e.g. fibroblasts, endothelial
cells, macrophages) which constitute around 50% of the
total cellular content. From the functional viewpoint, it is,
of course, the mature adipocytes that are the pivotal cells
within adipose tissue.

This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry
© 2007 Queen’s Printer and Controller of HMSO; published with permission
Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1), 41–44 41
42 Adipocyte biology P. Trayhurn
The focus on white adipose tissue
There are several reasons why the role of white adipose
tissue in energy balance and obesity research has become a
current focus of research. An obvious point that has been
ignored until recently is that obesity is defined by the
expansion of adipose tissue mass and it must therefore be
central to our understanding of obesity. More specifically,
adipose tissue is now recognized as the source of key hor-
mones which play an important role in the regulation of
energy balance – particularly leptin – and adipocytes are
today recognized as secreting a diverse range of protein
factors and signals termed ‘adipokines’, which are involved
in overall metabolic regulation and increasingly considered
to be directly linked to the pathologies associated with
obesity.
White adipocytes
White adipocytes are major secretory cells, making adi-
pose tissue a key endocrine organ. Indeed, adipose tissue is
the largest endocrine organ in most humans – and cer-
tainly so in the overweight and obese. For example, in a
lean individual [body mass index (BMI) 22–23], approxi-
mately 20% of total body weight is adipose tissue, while
in an obese subject (BMI 30) almost half of body weight is
due to the tissue. There is a clear implication that even
minor metabolic changes in such a large secretory organ
have the potential to impact broadly on the body as a
whole.
Quantitatively, the most important secretion from adipo-
cytes is fatty acids, of which there is net release at periods
of negative energy balance (particularly fasting). In addi-
tion to fatty acids, several other lipid moieties are released
by fat cells; these include prostanoids, which are synthe-
sized by the tissue, and cholesterol and retinol, which are
not synthesized but rather are stored and subsequently
released. In addition, certain steroid hormone conversions
can take place within white adipocytes.
The ‘new’ component of the ‘secretome’ of adipocytes is
the wide range of protein factors and signals that are
released. These ‘adipokines’ (or ‘adipocytokines’) now
number in excess of 50 different molecular entities.
The adipokines
The adipokines are highly diverse in terms of protein struc-
ture and physiological function. They include classical
cytokines, growth factors and proteins of the alternative
complement system; they also include proteins involved in
the regulation of blood pressure, vascular haemostasis,
lipid metabolism, glucose homeostasis and angiogenesis.
Leptin is the adipokine which has received most atten-
tion. Its discovery in 1994, as the product of the Ob gene
This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry
Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1), 41–44
obesity reviews
in the genetically obese (ob/ob) mouse, was the pivotal
discovery which led to the realization that adipose tissue is
a critical endocrine organ. Leptin is an essential signal from
adipocytes to the hypothalamus in the control of appetite
and energy balance. Indeed, without functional leptin,
severe obesity ensues as in the ob/ob mouse and the human
homologues that have been described. Leptin is in practice
a pleiotropic hormone, its functions extending far wider
than appetite and energy balance to encompass a multiplic-
ity of actions, including acting as a signal in reproduction
and immunity.
Much attention has also been focused on adiponectin,
which is a hormone produced exclusively by adipocytes. In
contrast to most adipokines, and leptin in particular, the
expression and circulating levels of adiponectin fall in obe-
sity. A number of roles are attributed to adiponectin,
including the modulation of insulin sensitivity and vascular
function, as well as an anti-inflammatory action. Adiponec-
tin, like leptin, is a powerful example of an adipocyte-
derived hormone which interacts with other organs and
a wide range of physiological systems and metabolic
processes.
Inflammation and obesity
A number of inflammation-related proteins are released by
white adipocytes, as well as adiponectin, and these include
cytokines, chemokines and acute phase proteins. In addi-
tion to these factors, several other inflammation-related
adipokines are recognized, including leptin and the angio-
genic protein, vascular endothelial growth factor. In obe-
sity, the production of many of these adipokines increases
markedly and the tissue is in effect ‘inflamed’.
One of the most important recent developments in obe-
sity research is the emergence of the concept that obesity
is characterized by chronic mild inflammation – paralleling
the situation with other diseases. The basis for this view is
that the circulating level of several cytokines and acute
phase proteins associated with inflammation is increased in
the obese. As adipocytes secrete a number of cytokines and
acute phase proteins, it is considered that the expanded
adipose tissue mass contributes, either directly or indirectly,
to the increased production and circulating levels of inflam-
mation-related factors in obesity. In other words, the state
of inflammation in adipose tissue in obesity leads to an
increased production and release of inflammation-related
factors.
Close links, and even similarities, between adipocytes
and immune cells are increasingly evident. The inflamma-
tory state of adipose tissue in obesity has been high-
lighted by recent reports demonstrating that there is
extensive infiltration of the tissue by macrophages in the
obese. The arrival of macrophages is thought to lead to a
considerable amplification of the inflammatory state in
© 2007 Queen’s Printer and Controller of HMSO; published with permission
obesity reviews
white fat, through the cytokines and chemokines that
they secrete.
Adipose tissue and the diseases of obesity
The central change to the body in obesity is clearly the
increase in the amount of adipose tissue – which may
constitute more than half of total body mass in those
with a BMI that is in excess of the threshold of obesity. It
is not, however, only the total amount of fat that is
important, but also its distribution. Thus, a more central
fat deposition (‘android’ or ‘apples’, as opposed to
‘gynoid’ or ‘pears’) is associated with a greater risk of the
metabolic syndrome and several of the other diseases
linked to obesity. A key question is why visceral fat is
particularly significant in terms of obesity-associated
disorders, and a long-standing position is that it is the
proximity to the liver and the portal circulation that is
important.
The current view is that the inflammatory state of obesity
plays a key causal role in the development of type 2 diabe-
tes and the metabolic syndrome (which includes atheroscle-
rosis, hypertension and hyperlipidaemia) associated with
obesity. A central hypothesis is that it is the increases in
inflammation-related adipokine production that occur in
obesity that lead to the associated diseases. In this context,
the reduction in adiponectin in the obese is thought to be
of particular significance in view of the anti-inflammatory
effect of this adipokine. Alterations in fatty acid flux have
also been implicated.
Current research foci
As emphasized above, adipocyte biology is now a ‘hot’ area
of biomedical research. Much of the work centres on the
secreted protein signals and the secretory role of the tissue,
and it also includes the potential links between fatty acids
and the metabolic syndrome.
The key current areas of research are:
• the identification of the full range of proteins secreted
from fat cells – the ‘adipokinome’;
• describing the physiological processes with which the
adipokines are involved, and the extent to which adipo-
cytes are in ‘conversation’ with other cells, organs and
metabolic systems;
• identification of the changes in the secretion of specific
proteins when adipose tissue mass expands – and deter-
mining the potential pathological consequences of such
changes;
• the specific role of inflammation-related adipokines in
the development of type 2 diabetes and the metabolic
syndrome;
• the importance of macrophages in modulating adipose
tissue function in obesity;
This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry
© 2007 Queen’s Printer and Controller of HMSO; published with permission
Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1), 41–44
Adipocyte biology P. Trayhurn 43
• understanding the mechanistic basis for inflammation
of adipose tissue in obesity.
Additional areas of particular interest include an em-
phasis on the importance of blood flow to adipose tissue
function and dysfunction, and the concept that, as with
tumours, manipulation of angiogenesis could lead to a loss
of body fat.
Long-term perspective
A key area for the next few years will undoubtedly be
unravelling the role of inflammation in the development of
obesity-related diseases – not only type 2 diabetes and the
metabolic syndrome, but also cancer. Indeed, major insight
into the causes of cancer may come from investigating the
mechanistic link between adiposity and the development of
tumours – and would be expected to lead to new opportu-
nities for therapeutic intervention.
Predicting beyond the next decade is inevitably both
difficult and hazardous, a situation amply illustrated by the
fact that 20 years ago it was never envisaged that adipose
tissue might be an important endocrine organ. Neverthe-
less, realistic scenarios within the existing paradigms can
be entertained.
For example, treatment of obesity-related diseases might
be possible if the production and/or action of specific adi-
pokines, particularly those linked to inflammation, were to
be targeted. There are already potential routes through
which this might be achieved. Pharmacologically based
approaches include harnessing the anti-inflammatory
action of the new generation of anti-diabetic drugs – the
thiazolidinediones – which operate through the PPARγ
nuclear receptor. Nutritional intervention could also be
envisaged through anti-inflammatory n-3 polyunsaturated
fatty acids.
Nutritional genomics is likely to lead to the possibility
of individualized dietary advice based on genetic profiling
(specific polymorphisms); this could potentially be har-
nessed in terms of the modulation of adipokine production
to minimize disease risk. New appetite and energy balance
signals emanating from adipose tissue may be discovered,
which could be targeted to inhibit appetite. A better under-
standing of the basis for functional differences between
adipocytes in different depots (whether intrinsic or a reflec-
tion of local conditions) may lead to the possibility of
manipulating cells in detrimental depots – primarily vis-
ceral – towards those in more benign depots.
The concepts established through work on obesity will
flow to other areas – such as ‘healthy ageing’. Some of the
diseases of ageing, such as the metabolic syndrome and the
dementias, are linked to inflammation and it is speculated
that adipose tissue, through various adipokines, may play
an important and unexpected role in the aetiology of these
44 Adipocyte biology P. Trayhurn
diseases. This will be of special significance to an ageing
population and provides a potent example of how growing
knowledge of adipocyte biology is likely to impact in quite
unexpected ways on other areas and issues beyond obesity.
Conflict of Interest Statement
No conflict of interest was declared.
Further reading
1. Ahima RS. Central actions of adipocyte hormones. Trends
Endocrinol Metab 2005; 16: 307–313.
2. Berg AH, Scherer PE. Adipose tissue, inflammation, and car-
diovascular disease. Circ Res 2005; 96: 939–949.
3. Cinti S. The adipose organ: morphological perspectives of
adipose tissues. Proc Nutr Soc 2001; 60: 319–328.
4. Das UN. Is obesity an inflammatory condition? Nutrition 2001;
17: 953–966.
5. Frayn KN, Karpe F, Fielding BA, Macdonald IA, Coppack SW.
Integrative physiology of human adipose tissue. Int J Obes 2003;
27: 875–888.
6. Frühbeck G, Gómez-Ambrosi J, Muruzabal FJ, Burrell MA.
The adipocyte: a model for integration of endocrine and metabolic
signaling in energy metabolism regulation. Am J Physiol Endo-
crinol Metab 2001; 280: E827–E847.
This paper was commissioned by the Foresight programme of the Office of Science and Innovation, Department of Trade and Industry
Journal compilation © 2007 The International Association for the Study of Obesity. obesity reviews 8 (Suppl. 1), 41–44
obesity reviews
7. Harris RB. Leptin – much more than a satiety signal. Annu Rev
Nutr 2000; 20: 45–75.
8. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J
Clin Endocrinol Metab 2004; 89: 2548–2556.
9. Lazar MA. How obesity causes diabetes: not a tall tale. Science
2005; 307: 373–375.
10. Matsuzawa Y. Adipocytokines and metabolic syndrome.
Semin Vasc Med 2005; 5: 34–39.
11. Pond CM. Adipose tissue and the immune system. Prostag-
landins Leukot Essent Fatty Acids 2005; 73: 17–30.
12. Rajala MW, Scherer PE. The adipocyte – at the crossroads of
energy homeostasis, inflammation, and atherosclerosis. Endocri-
nology 2003; 144: 3765–3773.
13. Trayhurn P. Endocrine and signalling role of adipose tissue:
new perspectives on fat. Acta Physiol Scand 2005; 184: 285–293.
14. Trayhurn P, Beattie JH. Physiological role of adipose tissue:
white adipose tissue as an endocrine and secretory organ. Proc
Nutr Soc 2001; 60: 329–339.
15. Trayhurn P, Wood IS. Adipokines: inflammation and the
pleiotropic role of white adipose tissue. Br J Nut 2004; 92: 347–
355.
16. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory
changes in adipose tissue. J Clin Invest 2003; 112: 1785–1788.
17. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabe-
tes. J Clin Invest 2005; 115: 1111–1119.
18. Yudkin JS. Adipose tissue, insulin action and vascular disease:
inflammatory signals. Int J Obes 2003; 27(Suppl. 3): S25–S28.
© 2007 Queen’s Printer and Controller of HMSO; published with permission