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Metabolic adaptations in
weight loss
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AMRAPPHARMA
NUTRITION | TRAINING | FITNESS
Chapter 7: Metabolic adaptations to weight loss.
Weight loss is a period in which the failure rate is very high. It is a process in
which multiple mechanisms are involved, from psychological to physiological.
Today we live in an obesogenic environment, where ultra-processed foods
modify our homeostatic mechanism in different ways, like advertising, social networks,
impacting our reward mechanism, making it difficult to maintain and lose weight in the
medium/long term. term.
When trying to lose weight, be it for an aesthetic, sports or health goal, we cut
down on meal sizes, portions, etc., rather, we lower the amount of calories ingested
per day.
The body detects this and takes chemical/hormonal measures to counteract
and "protect" the organism from a possible starvation and fights to maintain the weight
or recover it once lost. This is done in different ways as we will explain below.
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Processes involved in the regulation of body weight
Under normal conditions, energy intake (food) is metabolized and used to fuel
basal metabolism, thermogenesis, and our energy expenditure (physical activity). Any
excess is stored as fat in fat cells for later use. There is a genetic contribution to
determining an individual's weight with early life events and parental guidance also
playing a role, but ultimately steady-state body weight is influenced by a number of
different factors. . These factors fall into three distinct but interrelated categories:
homeostatic, environmental, and behavioral processes.
Image 1: Factors involved in the energy balance
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(Image information) There are three main groups of factors (homeostatic, environmental,
and behavioral processes) that interact and influence steady-state body weight. Alterations in
any of these factors will result in changes in this steady state and could result in obesity. AgRP,
gout related peptide; GIP, gastric inhibitory polypeptide; GLP-1, glucagon-like peptide-1;
CART, cocaine and amphetamine regulated transcription; CCK, cholecystokinin; PYY, peptide
YY; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; PP, pancreatic polypeptide; REE,
resting energy expenditure; NREE, resting energy expenditure. 'Central' and 'peripheral' refer to
the site where the molecules are produced, rather than where they necessarily act. In the brain,
insulin acts as an anorexigenic hormone, 104, 105 In the periphery, however, insulin lowers
blood sugar, which powerfully stimulates food intake.
Homeostatic processes
Body weight is regulated by a complex neurohormonal system that reflects the
fundamental biological importance of energy balance and nutrient supply. In essence,
the signals involved in the homeostatic regulation of food intake, energy balance, and
body weight are centrally integrated in the arcuate nucleus of the hypothalamus,
caudal brainstem, and parts of the cortex and limbic system. Various neuropeptides
and hormones involved in appetite regulation function centrally in the hypothalamus;
some (for example, neuropeptide Y (NPY) and agouti-related peptide (AgRP)) are
orexigenic (stimulates hunger), while others (for example, pro-opiomelanocortin
(POMC) and cocaine-regulated transcription and amphetamine) are anorexigenic
(suppress hunger).
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The hypothalamus also processes peripheral signals that convey information
about short-term food intake (ie, nutrient availability) or long-term energy balance (ie,
energy stores) to achieve energy homeostasis.
A feedback loop is created between the brain and the periphery (gastrointestinal
tract, pancreas, liver, muscle, and adipose tissue).
Short-term signals include the orexigenic hormones ghrelin and gastric
inhibitory polypeptide; the anorexigenic hormones glucagon-like peptide-1 (GLP-1),
peptide YY (PYY), and cholecystokinin (CCK) of the gastrointestinal tract; the
anorexigenic hormones pancreatic polypeptide (PP), amylin, and insulin from the
pancreas; and the anorexigenic hormone leptin from adipocytes. Insulin, however, is
unique in that it reduces food intake centrally but causes weight gain when used
peripherally to treat diabetes.
The hypothalamus also integrates signals from 'hedonic' reward pathways into
the corticolimbic system, associated with palatability (eg sight, smell and taste) of
food. Such hedonic reward pathways can override the homeostatic system and
increase the desire to consume energy-dense foods, despite physiological satiety and
replete energy stores.
Various neurotransmitter systems in the brain, including dopaminergic,
opioidergic, and cannabinoid mechanisms, play important roles in reward pathways
and in mediating the pleasure drive from eating.
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Image 2: Physiological factors that promote weight recovery after loss.
(Image Information) Changes in specific parameters that drive weight regain are
indicated in red. AgRP, gout related peptide; GIP, gastric inhibitory polypeptide; GLP-1,
glucagon-like peptide-1; CART, cocaine and amphetamine regulated transcription; CCK,
cholecystokinin; PYY, peptide YY; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; PP,
pancreatic polypeptide; REE, resting energy expenditure; NREE, resting energy expenditure.
'Central' and 'peripheral' refer to the site where the molecules are produced, rather than where
they necessarily act. In the brain, insulin acts as an anorexigenic hormone. However, at the
periphery, insulin lowers blood sugar, which powerfully stimulates food intake.
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Environmental
The environment in which we live has an important role in influencing energy
homeostasis. An 'obesogenic' environment affects corticolimbic brain areas
related to learning and memory, reward, mood and emotion. Today it is not a
minor detail, since we are invaded by advertising, social networks, with
which the power of decision is influenced and jeopardizes correct decision-
making regarding food. Eating is necessary for survival and health, and is a
universal activity that involves many different food choice decisions. Food
choice decisions are often seen as mundane and arbitrary, but they can also
be seen as meaningful and symbolic. Food has become almost universally
available and accessible, so that anyone can buy it almost anywhere, at any
time. The deluge of options to make decisions about food choices leads many
people to experience too many opportunities to eat, what some label as "the
tyranny of choice"(1). Some food choice decisions do not lead to eating, but
people still must make the decision not to eat. People engage in multiple
eating and drinking episodes per day, and each eating episode requires many
types of decisions, including if, what, where, when, with whom, how long,
how, and how much to eat. Research has estimated that most people make
more than 220 food decisions per day. That decision-making about food
choices is a frequent and expected part of everyday life shows that it is a
salient and important topic that needs careful analysis.
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Food choice dynamism also occurs on a shorter time scale, with food choice
decisions varying across cycles of days, weeks, seasons, and years. Even
short episodes and events include changing moods for food choice decisions.
In addition to the above, other factors contributing to this environment
include the intense marketing of energy-dense foods, increased availability
of these foods, and larger portion sizes, presenting people with the
opportunity to overconsume large portions of energy. sugary/high-fat or
high-calorie foods. This increase in food intake is accompanied by decreases
in physical activity, for example, due to sedentary work, increased use of
vehicles, etc.
Behavioral
How we behave also influences our energy homeostasis. Clearly, simply
knowing that a healthy diet and exercise will result in weight loss is not enough to
achieve and maintain a healthy lifestyle and reduce excess body weight. Since it
requires not only having the knowledge of the facts, but also carrying it out, which is
precisely the complicated part.
Personal motivation for change can or does have a fundamental role in
changing unhealthy habits and lifestyles. It is clear that no unmotivated person
achieves a goal and more applies to a medium/long-term physical/physiological goal.
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Planning, time management and social support are also key when seeking to
reduce excess weight, since all these actions go through behavior, being associated
with positive changes.
It is important to plan food purchases, weekly planning to find time to train,
planning (if possible) a weekly menu.
Physiological adaptations to weight loss and factors that favor weight
regain.
Evidence continues to accumulate that compensatory changes in biological
pathways involved in appetite regulation, energy utilization and storage promote
weight regain after weight loss.
These changes affect our complex neurohormonal system that regulates
energy homeostasis, including disturbances in circulating hormone levels related to
appetite and energy homeostasis, as well as alterations in nutrient metabolism and
subjective appetite.
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Circulating hormone levels
Appetite-related hormones have a key role in weight regain after weight loss. Changes
in hormones after weight loss tend to promote weight regain by increasing hunger and
promoting energy storage.
For example, after diet-induced weight loss, there are increases in ghrelin, and gastric
inhibitory polypeptide levels with decreases in leptin, PYY, CCK, amylin, insulin, and
GLP-1 levels.
The body's energy stores, predominantly fat, are regulated by multiple systems that
conspire to defend these energy stores against energy imbalance and changes in
energy stores. Many of these systems are sensitive to leptin, but disproportionately
during attempts to maintain reduced energy stores rather than lose weight, and
energetic homeostatic responses are stronger to leptin depletion.
Circulating leptin concentrations in the fed state are determined by fat mass (number
of cells × size), that is, the greater the adipose tissue, the greater the leptin
concentration. However, if fat mass is reduced by caloric restriction, once leptin
concentration falls below threshold, specific neurons that sense this decrease invoke
behavioral (hunger) and metabolic (reduced energy expenditure) changes that have
the added effect of restoring body fat (leptin). The leptin receptor is highly expressed in
cells of the hypothalamic nuclei that play important roles in homeostatic regulation of
weight.
Despite the fact that circulating leptin concentrations are lower during weight loss
than during weight maintenance, individuals who maintain weight loss are clearly
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more sensitive to leptin replacement. These data suggest that the metabolic and
behavioral oppositions to sustained weight loss are a response to declining energy
stores rather than a "carry-over" effect of caloric restriction.
Energy balance
Energy expenditure varies with changes in body weight, and the balance
between ingested energy (in the form of calories) and the body's basal energy demand
is a fundamental determinant in body weight control. Maintenance of a reduced body
weight is associated with compensatory changes in energy expenditure, which tend to
favor weight gain. Diet-induced weight loss leads to a decrease in TEE, REE, and non-
REE. It is likely that the mechanisms involved in the decrease in TEE after weight loss
are related to a reduction in body mass and greater metabolic efficiency(2). The
reduction in energy expenditure occurs as a result of greater efficiency of chemo-
mechanical contraction of skeletal muscle. That is, in an analogy to automobile
performance, the underweight individual gets more miles per calorie of energy
expended to a degree beyond that predicted by weight loss alone. This remarkable
change in skeletal muscle physiology is consistent with the reduction in thyroid
hormone and sympathetic nerve activity that characterizes the reduced weight state.
Added to this, neural signaling related to energy intake (increased food reward
and impulsivity, delayed satiety) and neuroendocrine function (decreased circulating
concentrations of bioactive thyroid hormone), hormones, and leptin) cause a significant
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drop in basal energy expenditure, therefore, this translates into a lower energy
requirement through food.
All this together, as we can see, are coordinated changes in the desire to eat
(increase) and energy expenditure (decrease) as a result of weight loss, creating a
"perfect physiological storm" to regain weight, which is basically what it happens in
most cases.
These physiological changes that occur with weight loss may explain the most
common responses to diet-mediated weight loss, ie, early weight loss that plateaus at
1 year.
Image 3: Physiological Changes and Adaptations
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Nutrient metabolism
The composition of the diet used for weight loss may influence subsequent
weight regain.
It was suggested that a low carbohydrate diet may help protect against weight
regain.
Although these are details and of little relevance, it is very important that the
diet always stays above a range of 1.6 gr/kg of protein per day. Then the fats and
carbohydrates can be manipulated according to taste or convenience.
Subjective appetite
Eating stimulates the brain centers involved in pleasure and reward, which helps
explain why the motivation to consume food, possibly even despite a state of satiety,
goes beyond the need to maintain energy homeostasis and weight. bodily.
It is likely that overeating reflects an imbalance in the control exerted by the
hypothalamus over reward circuitry and/or a change in the hedonic set point for food
reward, causing a perfect circuit to require more and more palatable food. to reach
that level of “pleasure”.
Interestingly, a reduction in striatal dopamine D2 receptors has been shown in
overweight individuals, which may lead to excessive food consumption as a means of
compensating for decreased activation of the dopamine pathway. This means that
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weight loss has another complicating factor and it is this neurotransmitter involved in
the reward mechanism.
Evidence shows that diet-induced weight loss in overweight adults is accompanied
by an increase in all components of appetite.(3)
Dietary intake and overestimation of consumption
Following all of the above, ad libitum food intake can be problematic when it
comes to weight loss.
Most normal weight and overweight people overestimate daily energy intake.
In many studies (4,5) it can be observed that food reports disagree with the
energy that people think they ingest, it can even vary from 20 to 150%.
It is recommended that standardized food tracking be present during the
process, or calorie tracking in some way, as today's foods and products are
not the same as in the past to keep the homeostatic system efficient, as well
as we could. Observe before, food is crossed by many factors, also affecting
intake and food perception.
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Conclusión
Weight loss is a complex goal in the times in which we live. Physiological, metabolic,
and behavioral adaptations are efficient functioning factors for weight gain and
recovery.
The obesogenic environment, advertising and social networks are an important factor
when making decisions and we must keep this in mind.
It is important to stay motivated and have support from someone or a team in this
objective, since it is an objective with a high dropout rate.
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BIBLIOGRAPHY
1. Constructing Food Choice Decisions | Annals of Behavioral Medicine | Oxford
Academic [Internet]. [citado 31 de mayo de 2023]. Disponible en:
https://academic.oup.com/abm/article/38/suppl_1/s37/4569654?login=false
2. Describiendo el Estado de Peso Reducido: Fisiología, Comportamiento e
Intervenciones - PMC [Internet]. [citado 29 de mayo de 2023]. Disponible en:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022199/
3. Adaptaciones fisiológicas a la pérdida de peso y factores que favorecen la
recuperación de peso - PMC [Internet]. [citado 28 de mayo de 2023]. Disponible en:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766925/
4. Hombres y mujeres con peso normal sobrestiman el gasto de energía durante
el ejercicio - PubMed [Internet]. [citado 1 de junio de 2023]. Disponible en:
https://pubmed.ncbi.nlm.nih.gov/21178922/
5. Self-reported energy intake by FFQ compared with actual energy intake to
maintain body weight in 516 adults - PubMed [Internet]. [citado 1 de junio de 2023].
Disponible en: https://pubmed.ncbi.nlm.nih.gov/21338536/
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AP Institute

NUTRITION | TRAINING | FITNESS

Chapter 7: Metabolic adaptations to weight loss.

which multiple mechanisms are involved, from psychological to physiological.

Today we live in an obesogenic environment, where ultra-processed foods

medium/long term. term.

The body detects this and takes chemical/hormonal measures to counteract

playing a role, but ultimately steady-state body weight is influenced by a number of

homeostatic, environmental, and behavioral processes.

Image 1: Factors involved in the energy balance

YY; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; PP, pancreatic polypeptide; REE,

blood sugar, which powerfully stimulates food intake.

Body weight is regulated by a complex neurohormonal system that reflects the

fundamental biological importance of energy balance and nutrient supply. In essence,

and hormones involved in appetite regulation function centrally in the hypothalamus;

orexigenic (stimulates hunger), while others (for example, pro-opiomelanocortin

(POMC) and cocaine-regulated transcription and amphetamine) are anorexigenic

energy stores) to achieve energy homeostasis.

tract, pancreas, liver, muscle, and adipose tissue).

Short-term signals include the orexigenic hormones ghrelin and gastric

inhibitory polypeptide; the anorexigenic hormones glucagon-like peptide-1 (GLP-1),

peptide YY (PYY), and cholecystokinin (CCK) of the gastrointestinal tract; the

peripherally to treat diabetes.

replete energy stores.

Various neurotransmitter systems in the brain, including dopaminergic,

opioidergic, and cannabinoid mechanisms, play important roles in reward pathways

and in mediating the pleasure drive from eating.

glucagon-like peptide-1; CART, cocaine and amphetamine regulated transcription; CCK,

cholecystokinin; PYY, peptide YY; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; PP,

The environment in which we live has an important role in influencing energy

homeostasis. An 'obesogenic' environment affects corticolimbic brain areas

minor detail, since we are invaded by advertising, social networks, with

which the power of decision is influenced and jeopardizes correct decision-

be seen as meaningful and symbolic. Food has become almost universally

choices is a frequent and expected part of everyday life shows that it is a

salient and important topic that needs careful analysis.

In addition to the above, other factors contributing to this environment

include the intense marketing of energy-dense foods, increased availability

opportunity to overconsume large portions of energy. sugary/high-fat or

high-calorie foods. This increase in food intake is accompanied by decreases

in physical activity, for example, due to sedentary work, increased use of

How we behave also influences our energy homeostasis. Clearly, simply

precisely the complicated part.

Personal motivation for change can or does have a fundamental role in

changing unhealthy habits and lifestyles. It is clear that no unmotivated person

achieves a goal and more applies to a medium/long-term physical/physiological goal.

with positive changes.

It is important to plan food purchases, weekly planning to find time to train,

planning (if possible) a weekly menu.

Physiological adaptations to weight loss and factors that favor weight

Evidence continues to accumulate that compensatory changes in biological

pathways involved in appetite regulation, energy utilization and storage promote

weight regain after weight loss.

These changes affect our complex neurohormonal system that regulates

energy homeostasis, including disturbances in circulating hormone levels related to

appetite and energy homeostasis, as well as alterations in nutrient metabolism and

promoting energy storage.

energetic homeostatic responses are stronger to leptin depletion.

concentration. However, if fat mass is reduced by caloric restriction, once leptin

behavioral oppositions to sustained weight loss are a response to declining energy

stores rather than a "carry-over" effect of caloric restriction.

is a fundamental determinant in body weight control. Maintenance of a reduced body

weight is associated with compensatory changes in energy expenditure, which tend to