Metabolic adaptation to weight loss: Implications for the athlete

Abstract

Optimized body composition provides a competitive advantage in a variety of sports. Weight reduction is common among athletes aiming to improve their strength-to-mass ratio, locomotive efficiency, or aesthetic appearance. Energy restriction is accompanied by changes in circulating hormones, mitochondrial efficiency, and energy expenditure that serve to minimize the energy deficit, attenuate weight loss, and promote weight regain. The current article reviews the metabolic adaptations observed with weight reduction and provides recommendations for successful weight reduction and long term reduced-weight maintenance in athletes.

Full text

R E V I E W Open Access
Metabolic adaptation to weight loss: implications
for the athlete
Eric T Trexler
1
, Abbie E Smith-Ryan
1*
and Layne E Norton
2
Abstract
Optimized body composition provides a competitive advantage in a variety of sports. Weight reduction is common
among athletes aiming to improve their strength-to-mass ratio, locomotive efficiency, or aesthetic appearance.
Energy restriction is accompanied by changes in circulating hormones, mitochondrial efficiency, and energy
expenditure that serve to minimize the energy deficit, attenuate weight loss, and promote weight regain. The
current article reviews the metabolic adaptations observed with weight reduction and provides recommendations
for successful weight reduction and long term reduced-weight maintenance in athletes.
Keywords: Weight loss, Energy restriction, Body composition, Energy expenditure, Metabolic rate, Energy deficit,
Weight maintenance, Uncoupling proteins, Mitochondrial efficiency
Introduction
In a variety of competitive sports, it is considered advan-
tageous to achieve low levels of body fat while retaining
lean body mass. The metabolic effects of this process
have been given little context within athletics, such as
physique sports (i.e. bodybuilding, figure), combat sports
(i.e. judo, wrestling), aesthetic sports (i.e. gymnastics,
figure skating), and endurance sports. Previous literature
has documented cases of male bodybuilders reducing
body fat to less than 5% of total body mass [1,2], and
studies documenting physiological profiles of male wres-
tlers [3] and judo athletes [4] present body fat ranges
that extend below 5%. A study on elite female gymnasts
and runners reported an average body fat percentage
(BF%) of 13.72% for the entire sample, with subgroups
of middle-distance runners and artistic gymnasts aver-
aging 12.18% and 12.36%, respectively [5]. Elite female
runners have also reported percent body fat levels below
10% [6]. Energy deficits and extremely low levels of body
fat present the body with a significant physiological chal-
lenge. It has been well documented that weight loss and
energy restriction result in a number of homeostatic
metabolic adaptations aimed at decreasing energy ex-
penditure, improving metabolic efficiency, and increasing
cues for energy intake [7-9]. While the unfavorable endo-
crine effects of contest preparation have been documented
in male bodybuilders [1,2,10], anecdotal reports from phys-
ique athletes also describe a state in which metabolic rate
has slowed to an extent that exceeds the predicted magni-
tude, making weight loss increasingly difficult despite low
caloric intakes and high training volumes. Although such
reports could potentially be related to inaccurate dietary
reporting [11,12], these claims may be substantiated by a
number of metabolic adaptations to weight loss, including
adaptive thermogenesis [13-15], increased mitochondrial
efficiency [16-19], and hormonal alterations that favor
decreased energy expenditure, decreased satiety, and in-
creased hunger [1,2,10]. As a dieting phase progresses,
such adaptations may threaten dietary adherence, make
further weight loss increasingly difficult, and predispose
the individual to rapid weight regain following the cessa-
tion of the diet. Although data documenting the attain-
ment and recovery from extreme changes in body
composition is limited, the present article aims to investi-
gate the condition of metabolic adaptation described by
competitors and identify potential mechanisms to explain
such a phenomenon.
The endocrine response to an energy deficit
A number of hormones play prominent roles in the
regulation of body composition, energy intake, and en-
ergy expenditure. The hormones of the thyroid gland,
* Correspondence: abbsmith@email.unc.edu
1
Department of Exercise and Sport Science, University of North Carolina at
Chapel Hill, 209 Fetzer Hall, CB# 8700, Chapel Hill, NC 27599-8700, USA
Full list of author information is available at the end of the article
© 2014 Trexler et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
Trexler et al. Journal of the International Society of Sports Nutrition 2014, 11:7
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particularly triiodothyronine (T3), are known to play an
important and direct role in regulating metabolic rate.
Increases in circulating thyroid hormones are associated
with an increase in the metabolic rate, whereas lowered
thyroid levels result in decreased thermogenesis and
overall metabolic rate [20]. Leptin, synthesized primarily
in adipocytes, functions as an indicator of both short
and long-term energy availability; short-term energy
restriction and lower body fat levels are associated with
decreases in circulating leptin. Additionally, higher con-
centrations of leptin are associated with increased satiety
and energy expenditure [21]. Insulin, which plays a cru-
cial role in inhibiting muscle protein breakdown [22]
and regulating macronutrient metabolism, is considered
another “adiposity signal”[23]. Similar to leptin, high
levels of insulin convey a message of energy availability
and are associated with an anorexigenic effect. Con-
versely, the orexigenic hormone ghrelin functions to
stimulate appetite and food intake, and has been shown
to increase with fasting, and decrease after feeding [24].
Testosterone, known primarily for its role in increasing
muscle protein synthesis and muscle mass [22], may also
play a role in regulating adiposity [25]. Changes in fat
mass have been inversely correlated with testosterone
levels, and it has been suggested that testosterone may
repress adipogenesis [25]. More research is needed to
delineate the exact mechanism (s) by which testosterone
affects adiposity. Cortisol, a glucocorticoid that influ-
ences macronutrient metabolism, has been shown to
induce muscle protein breakdown [22], and increased
plasma cortisol within the physiologic range has in-
creased proteolysis in healthy subjects [26]. Evidence
also suggests that glucocorticoids may inhibit the action
of leptin [27].
Results from a number of studies indicate a general
endocrine response to hypocaloric diets that promotes
increased hunger, reduces metabolic rate, and threatens
the maintenance of lean mass. Studies involving energy
restriction, or very low adiposity, report decreases in
leptin [1,10,28], insulin [1,2], testosterone [1,2,28], and thy-
roid hormones [1,29]. Subsequently, increases in ghrelin
[1,10] and cortisol [1,30,31] have been reported with en-
ergy restriction. Further, there is evidence to suggest that
unfavorable changes in circulating hormone levels persist
as subjects attempt to maintain a reduced body weight,
even after the cessation of active weight loss [32,33].
Low energy intake and minimal body fat are perceived
as indicators of energy unavailability, resulting in a
homeostatic endocrine response aimed at conserving en-
ergy and promoting energy intake. It should be noted
that despite alterations in plasma levels of anabolic and
catabolic hormones, losses of lean body mass (LBM)
often fail to reach statistical significance in studies on
bodybuilding preparation [1,2]. Although the lack of
significance may relate to insufficient statistical power,
these findings may indicate that unfavorable, hormone-
mediated changes in LBM can potentially be attenuated
by sound training and nutritional practices. Previous re-
search has indicated that structured resistance training
[34] and sufficient protein intake [35-37], both com-
monly employed in bodybuilding contest preparation,
preserve LBM during energy restriction. Further, Maestu
et al. speculate that losses in LBM are dependent on the
magnitude of weight loss and degree of adiposity, as the
subjects who lost the greatest amount of weight and
achieved the lowest final body fat percentage in the study
saw the greatest losses of LBM [2]. The hormonal envir-
onment created by low adiposity and energy restriction
appears to promote weight regain and threaten lean mass
retention, but more research is needed to determine the
chronic impact of these observed alterations in circulat-
ing anabolic and catabolic hormones.
Weight loss and metabolic rate
An individual’s total daily energy expenditure (TDEE)
is comprised of a number of distinct components
(Figure 1). The largest component, resting energy ex-
penditure (REE), refers to the basal metabolic rate
(BMR) [8]. The other component, known as non-resting
energy expenditure (NREE), can be further divided into
exercise activity thermogenesis (EAT), non-exercise ac-
tivity thermogenesis (NEAT), and the thermic effect of
food (TEF) [8].
Figure 1 Components of total daily energy expenditure (TDEE).
BMR = basal metabolic rate; NEAT = non-exercise activity thermogenesis;
TEF = thermic effect of food; EAT = exercise activity thermogenesis;
REE = resting energy expenditure; NREE = non-resting energy
expenditure. Adapted from Maclean et al., 2011.
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Metabolic rate is dynamic in nature, and previous lit-
erature has shown that energy restriction and weight
loss affect numerous components of energy expenditure.
In weight loss, TDEE has been consistently shown to de-
crease [38,39]. Weight loss results in a loss of metabolic-
ally active tissue, and therefore decreases BMR [38,39].
Interestingly, the decline in TDEE often exceeds the
magnitude predicted by the loss of body mass. Previous
literature refers to this excessive drop in TDEE as adap-
tive thermogenesis, and suggests that it functions to pro-
mote the restoration of baseline body weight [13-15].
Adaptive thermogenesis may help to partially explain the
increasing difficulty experienced when weight loss plat-
eaus despite low caloric intake, and the common pro-
pensity to regain weight after weight loss.
Exercise activity thermogenesis also drops in response
to weight loss [40-42]. In activity that involves locomo-
tion, it is clear that reduced body mass will reduce the
energy needed to complete a given amount of activity.
Interestingly, when external weight is added to match
the subject’s baseline weight, energy expenditure to
complete a given workload remains below baseline [41].
It has been speculated that this increase in skeletal
muscle efficiency may be related to the persistent
hypothyroidism and hypoleptinemia that accompany
weight loss, resulting in a lower respiratory quotient and
greater reliance on lipid metabolism [43].
The TEF encompasses the energy expended in the
process of ingesting, absorbing, metabolizing, and stor-
ing nutrients from food [8]. Roughly 10% of TDEE is at-
tributed to TEF [44,45], with values varying based on the
macronutrient composition of the diet. While the rela-
tive magnitude of TEF does not appear to change with
energy restriction [46], such dietary restriction involves
the consumption of fewer total calories, and therefore
decreases the absolute magnitude of TEF [41,46]. NEAT,
or energy expended during “non-exercise”movement
such as fidgeting or normal daily activities, also de-
creases with an energy deficit [47]. There is evidence to
suggest that spontaneous physical activity, a component
of NEAT, is decreased in energy restricted subjects, and
may remain suppressed for some time after subjects re-
turn to ad libitum feeding [29]. Persistent suppression
of NEAT may contribute to weight regain in the post-
diet period.
In order to manipulate an individual’s body mass, en-
ergy intake must be adjusted based on the individual’s
energy expenditure. In the context of weight loss or
maintaining a reduced body weight, this process is com-
plicated by the dynamic nature of energy expenditure. In
response to weight loss, reductions in TDEE, BMR, EAT,
NEAT, and TEF are observed. Due to adaptive thermo-
genesis, TDEE is lowered to an extent that exceeds the
magnitude predicted by losses in body mass. Further,
research indicates that adaptive thermogenesis and de-
creased energy expenditure persist after the active weight
loss period, even in subjects who have maintained a re-
duced body weight for over a year [14,48]. These changes
serve to minimize the energy deficit, attenuate further loss
of body mass, and promote weight regain in weight-
reduced subjects.
Adaptations in mitochondrial efficiency
A series of chemical reactions must take place to derive
ATP from stored and ingested energy substrates. In aer-
obic metabolism, this process involves the movement
of protons across the inner mitochondrial membrane.
When protons are transported by ATP synthase, ATP is
produced. Protons may also leak across the inner mem-
brane by way of uncoupling proteins (UCPs) [49]. In this
“uncoupled respiration”, energy substrate oxidation and
oxygen consumption occur, but the process does not
yield ATP. Proton leak is a significant contributor to
energy expenditure, accounting for roughly 20-30% of
BMR in rats [50-52].
In the condition of calorie restriction, proton leak is
reduced [16-19]. Uncoupling protein-1 and UCP-3, the
primary UCPs of brown adipose tissue (BAT) and skel-
etal muscle [53], are of particular interest due to their
potentially significant roles in energy expenditure and
uncoupled thermogenesis. Skeletal muscle’s large contri-
bution to energy expenditure [54] has directed attention
toward literature reporting decreases in UCP-3 expres-
sion in response to energy restriction [55,56]. Decreased
UCP-3 expression could potentially play a role in de-
creasing energy expenditure, and UCP-3 expression has
been negatively correlated with body mass index and
positively correlated with metabolic rate during sleep
[57]. Despite these correlations, more research is needed
to determine the function and physiological relevance of
UCP-3 [58], as contradictory findings regarding UCP-3
and weight loss have been reported [18].
Uncoupling Protein-1 appears to play a pivotal role in
the uncoupled thermogenic activity of BAT [59]. Energy
restriction has been shown to decrease BAT activation
[60] and UCP-1 expression [61], indicating an increase
in metabolic efficiency. Along with UCP-1 expression,
thyroid hormone and leptin affect the magnitude of
uncoupled respiration in BAT. Thyroid hormone (TH)
and leptin are associated with increased BAT activation,
whereas glucocorticoids oppose the BAT-activating func-
tion of leptin [59]. Evidence indicates that TH plays a
prominent role in modulating the magnitude of proton
leak [53], with low TH levels associated with decreased
proton leak [62]. The endocrine response to energy re-
striction, including increased cortisol and decreased TH
and leptin [1,10,28-31], could potentially play a regula-
tory role in uncoupled respiration in BAT. It is not clear
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if decreases in proton leak and UCP expression persist
until weight reverts to baseline, but there is evidence to
suggest a persistent adaptation [19,55,56], which mirrors
the persistent downregulation of TH and leptin [32,33].
Changes observed in proton leak, UCP expression, and
circulating hormones appear to influence metabolic effi-
ciency and energy expenditure. In the context of energy
restriction, the observed changes are likely to make
weight loss increasingly challenging and promote weight
regain. It has been reported that females have more BAT
than males [63], and that energy-restricted female rats
see greater decreases in BAT mass and UCP-1 than
males [64], indicating a potential sex-related difference
in uncoupled respiration during weight loss. Subjects
identified as “diet-resistant”show decreased proton leak
and UCP-3 expression compared to “diet-responsive”
subjects during maintenance of a reduced bodyweight
[65]. More research is needed to determine if these dif-
ferential responses to hypocaloric diets make sustained
weight loss more difficult for females and certain predis-
posed “diet-resistant”individuals. While future research
may improve our understanding of the magnitude and
relative importance of mitochondrial adaptations to en-
ergy restriction, current evidence suggests that increased
mitochondrial efficiency, and a decline in uncoupled res-
piration, might serve to decrease the energy deficit in
hypocaloric conditions, making weight maintenance and
further weight reduction more challenging.
Practical applications for weight loss in athletes
Hypocaloric diets induce a number of adaptations that
serve to prevent further weight loss and conserve energy.
It is likely that the magnitude of these adaptations are
proportional to the size of the energy deficit, so it is rec-
ommended to utilize the smallest possible deficit that
yields appreciable weight loss. This may decrease the
rate of weight loss, but attenuate unfavorable adapta-
tions that challenge successful reduction of fat mass.
Weight reduction should be viewed as a stepwise
process in this context; as weight loss begins to plateau,
energy intake or expenditure should be adjusted to
“re-open”theenergydeficit.Large caloric deficits are
also likely to induce greater losses of LBM [66,67] and
compromise athletic performance and recovery [68,69],
which are of critical importance to athletes. Participation
in a structured resistance training program [34] and suffi-
cient protein intake [35-37] are also likely to attenuate
losses in LBM. Additionally, high protein diets (≥25%
PRO) are associated with increased satiety and thermo-
genesis, making them a better option for the calorie-
restricted athlete [70].
In the world of physique sports, periodic “refeeding”
has become common in periods of extended dieting. A
refeed consists of a brief overfeeding period in which
caloric intake is raised slightly above maintenance levels,
and the increase in caloric intake is predominantly
achieved by increasing carbohydrate consumption. While
studies have utilized refeeding protocols that last three
days [71,72], physique athletes such as bodybuilders and
figure competitors often incorporate 24-hour refeeds,
once or twice per week. The proposed goal of periodic
refeeding is to temporarily increase circulating leptin and
stimulate the metabolic rate. There is evidence indicating
that leptin is acutely responsive to short-term overfeed-
ing [72], is highly correlated with carbohydrate intake
[71,73], and that pharmacological administration of lep-
tin reverses many unfavorable adaptations to energy re-
striction [33]. While interventions have shown acute
increases in leptin from short-term carbohydrate over-
feeding, the reported effect on metabolic rate has been
modest [71]. Dirlewanger et al. reported a 7% increase in
TDEE; this increase amounts to approximately 138 kilo-
calories of additional energy expenditure, of which 36
kilocalories can be attributed to the thermic effect of
carbohydrate intake [71]. More research is needed to de-
termine if acute bouts of refeeding are an efficacious
strategy for improving weight loss success during pro-
longed hypocaloric states. A theoretical model of meta-
bolic adaptation and potential strategies to attenuate
adaptations is presented in Figure 2.
In the period shortly after cessation of a restrictive
diet, body mass often reverts toward pre-diet values
[29,74,75]. This body mass is preferentially gained as fat
mass, in a phenomenon known as post-starvation obes-
ity [29]. While many of the metabolic adaptations to
weight loss persist, a dramatic increase in energy intake
results in rapid accumulation of fat mass. It is common
for individuals to “overshoot”their baseline level of body
fat, and leaner individuals (including many athletes) may
be more susceptible to overshooting than obese individ-
uals [74,75]. In such a situation, the individual may
increase body fat beyond baseline levels, yet retain a
metabolic rate that has yet to fully recover. There is evi-
dence to suggest that adipocyte hyperplasia may occur
early in the weight-regain process [76], and that repeated
cycles of weight loss and regain by athletes in sports
with weight classes are associated with long-term weight
gain [77]. Therefore, athletes who aggressively diet for a
competitive season and rapidly regain weight may find it
more challenging to achieve optimal body composition
in subsequent seasons.
To avoid rapid fat gain following the cessation of a
diet, “reverse dieting”has also become popular among
physique athletes. Such a process involves slowly in-
creasing caloric intake in a stepwise fashion. In theory,
providing a small caloric surplus might help to restore
circulating hormone levels and energy expenditure
toward pre-diet values, while closely matching energy
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intake to the recovering metabolic rate in an effort to re-
duce fat accretion. Ideally, such a process would eventu-
ally restore circulating hormones and metabolic rate to
baseline levels while avoiding rapid fat gain. While anec-
dotal reports of successful reverse dieting have led to an
increase in its popularity, research is needed to evaluate
its efficacy.
Limitations
Although there is a substantial body of research on
metabolic adaptations to weight loss, the majority of the
research has utilized animal models or subjects that
are sedentary and overweight/obese. Accordingly, the
current article is limited by the need to apply this data
to an athletic population. If the adaptations described in
obese populations serve to conserve energy and attenu-
ate weight loss as a survival mechanism, one might
speculate that the adaptations may be further augmented
in a leaner, more highly active population. Another limi-
tation is the lack of research on the efficacy of periodic
refeeding or reverse dieting in prolonged weight reduc-
tion, or in the maintenance of a reduced bodyweight.
Until such research is available, these anecdotal methods
can only be evaluated from a mechanistic and theoretical
viewpoint.
Conclusion
Weight loss is a common practice in a number of sports.
Whether the goal is a higher strength-to-mass ratio,
improved aesthetic presentation, or more efficient loco-
motion, optimizing body composition is advantageous to
a wide variety of athletes. As these athletes create an en-
ergy deficit and achieve lower body fat levels, their
weight loss efforts will be counteracted by a number
of metabolic adaptations thatmaypersistthroughout
weight maintenance. Changes in energy expenditure,
Figure 2 A theoretical model of metabolic adaptation and potential strategies to attenuate adaptations. A/A/T hormones = Anabolic,
Anorexigenic, and Thermogenic hormones; O/C hormones =Orexigenic and Catabolic hormones. Dotted lines represent inhibition.
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mitochondrial efficiency, and circulating hormone con-
centrations work in concert to attenuate further weight
loss and promote the restoration of baseline body mass.
Athletes must aim to minimize the magnitude of these
adaptations, preserve LBM, and adequately fuel perform-
ance and recovery during weight reduction. To accom-
plish these goals, it is recommended to approach weight
loss in a stepwise, incremental fashion, utilizing small en-
ergy deficits to ensure a slow rate of weight loss. Partici-
pation in a structured resistance training program and
adequate protein intake are also imperative. More re-
search is needed to verify the efficacy of periodic refeed-
ing and reverse dieting in supporting prolonged weight
reduction and attenuating post-diet fat accretion.
Abbreviations
BAT: Brown adipose tissue; BF%: Body fat percentage; BMR: Basal metabolic
rate; EAT: Exercise activity the rmoge nesis; LBM: Le an body mass;
NEAT: Non-exercise activity thermogenesis; NREE: Non-resting energy
expenditure; REE: Resting energy expenditure; TDEE: Total daily energy
expenditure; TEF: Thermic effect of food; TH: Thyroid Hormone;
T3: Triiodothyronine; UCP: Uncoupling protein.
Competing interests
The authors declare that they have no competing interests.
Authors’contributions
ETT conceived of the review topic and drafted the manuscript. AES
conceived, drafted and revised the manuscript. LEN helped to draft and
revise the manuscript. All authors read and approved the final manuscript.
Author details
1
Department of Exercise and Sport Science, University of North Carolina at
Chapel Hill, 209 Fetzer Hall, CB# 8700, Chapel Hill, NC 27599-8700, USA.
2
BioLayne LLC, Tampa, FL, USA.
Received: 18 December 2013 Accepted: 20 February 2014
Published: 27 February 2014
References
1. Rossow LM, Fukuda DH, Fahs CA, Loenneke JP, Stout JR: Natural
bodybuilding competition preparation and recovery: a 12-month case
study. Int J Sports Physiol Perform 2013, 8:582–592.
2. Maestu J, Eliakim A, Jurimae J, Valter I, Jurimae T: Anabolic and catabolic
hormones and energy balance of the male bodybuilders during the
preparation for the competition. J Strength Cond Res 2010, 24:1074–1081.
3. Yoon J: Physiological profiles of elite senior wrestlers. Sports Med 2002,
32:225–233.
4. Franchini E, Del Vecchio FB, Matsushigue KA, Artioli GG: Physiological
profiles of elite judo athletes. Sports Med 2011, 41:147–166.
5. Deutz RC, Benardot D, Martin DE, Cody MM: Relationship between energy
deficits and body composition in elite female gymnasts and runners.
Med Sci Sports Exerc 2000, 32:659–668.
6. Wilmore JH, Brown CH, Davis JA: Body physique and composition of the
female distance runner. Ann N Y Acad Sci 1977, 301:764–776.
7. Dulloo AG, Jacquet J: Adaptive reduction in basal metabolic rate in
response to food deprivation in humans: a role for feedback signals
from fat stores. Am J Clin Nutr 1998, 68:599–606.
8. Maclean PS, Bergouignan A, Cornier MA, Jackman MR: Biology’s response
to dieting: the impetus for weight regain. Am J Physiol Regul Integr Comp
Physiol 2011, 301:R581–R600.
9. MacLean PS, Higgins JA, Jackman MR, Johnson GC, Fleming-Elder BK, Wyatt HR,
Melanson EL, Hill JO: Peripheral metabolic responses to prolonged weight
reduction that promote rapid, efficient regain in obesity-prone rats. Am J
Physiol Regul Integr Comp Physiol 2006, 290:R1577–R1588.
10. Maestu J, Jurimae J, Valter I, Jurimae T: Increases in ghrelin and decreases
in leptin without altering adiponectin during extreme weight loss in
male competitive bodybuilders. Metabolism 2008, 57:221–225.
11. Lichtman SW, Pisarska K, Berman ER, Pestone M, Dowling H, Offenbacher E,
Weisel H, Heshka S, Matthews DE, Heymsfield SB: Discrepancy between
self-reported and actual caloric intake and exercise in obese subjects.
N Engl J Med 1992, 327:1893–1898.
12. Garriguet D: Under-reporting of energy intake in the Canadian
community health survey. Health Rep 2008, 19:37–45.
13. Doucet E, St-Pierre S, Almeras N, Despres JP, Bouchard C, Tremblay A:
Evidence for the existence of adaptive thermogenesis during
weight loss. Br J Nutr 2001, 85:715–723.
14. Rosenbaum M, Hirsch J, Gallagher DA, Leibel RL: Long-term persistence of
adaptive thermogenesis in subjects who have maintained a reduced
body weight. Am J Clin Nutr 2008, 88:906–912.
15. Rosenbaum M, Leibel RL: Adaptive thermogenesis in humans. Int J Obes
2010, 34(Suppl 1):S47–S55.
16. Asami DK, McDonald RB, Hagopian K, Horwitz BA, Warman D, Hsiao A, Warden C,
Ramsey JJ: Effect of aging, caloric restriction, and uncoupling protein 3 (UCP3)
on mitochondrial proton leak in mice. Exp Gerontol 2008, 43:1069–1076.
17. Bevilacqua L, Ramsey JJ, Hagopian K, Weindruch R, Harper ME: Effects of
short- and medium-term calorie restriction on muscle mitochondrial
proton leak and reactive oxygen species production. Am J Physiol
Regul Integr Comp Physiol 2004, 286:E852–E861.
18. Bevilacqua L, Ramsey JJ, Hagopian K, Weindruch R, Harper ME: Long-term
caloric restriction increases UCP3 content but decreases proton leak and
reactive oxygen species production in rat skeletal muscle mitochondria.
Am J Physiol Endocrinol Metab 2005, 289:E429–E438.
19. Hagopian K, Harper ME, Ram JJ, Humble SJ, Weindruch R, Ramsey JJ:
Long-term calorie restriction reduces proton leak and hydrogen
peroxide production in liver mitochondria. Am J Physiol Endocrinol
Metab 2005, 288:E674–E684.
20. Kim B: Thyroid hormone as a determinant of energy expenditure and
the basal metabolic rate. Thyroid 2008, 18:141–144.
21. Margetic S, Gazzola C, Pegg GG, Hill RA: Leptin: a review of its
peripheral actions and interactions. IntJObesRelatMetabDisord
2002, 26:1407–1433.
22. Rooyackers OE, Nair KS: Hormonal regulation of human muscle protein
metabolism. Annu Rev Nutr 1997, 17:457–485.
23. Strohacker K, McCaffery JM, Maclean PS, Wing RR: Adaptations of leptin,
ghrelin or insulin during weight loss as predictors of weight regain: a
review of current literature. Int J Obes 2013:1–9. http://www.nature.com/
ijo/journal/vaop/ncurrent/full/ijo2013118a.html.
24. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T,
Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A, Doi K, Hosoda H, Kojima M,
Kangawa K, Nakao K: Stomach is a major source of circulating ghrelin, and
feeding state determines plasma ghrelin-like immunoreactivity levels in
humans. J Clin Endocrinol Metab 2001, 86:4753–4758.
25. De Maddalena C, Vodo S, Petroni A, Aloisi AM: Impact of testosterone on
body fat composition. J Cell Physiol 2012, 227:3744–3748.
26. Simmons PS, Miles JM, Gerich JE, Haymond MW: Increased proteolysis. An
effect of increases in plasma cortisol within the physiologic range. J Clin
Invest 1984, 73:412–420.
27. Zakrzewska KE, Cusin I, Sainsbury A, Rohner-Jeanrenaud F, Jeanrenaud B:
Glucocorticoids as counterregulatory hormones of leptin: toward an
understanding of leptin resistance. Diabetes 1997, 46:717–719.
28. Hagmar M, Berglund B, Brismar K, Hirschberg AL: Body composition and
endocrine profile of male Olympic athletes striving for leanness. Clin J
Sport Med 2013, 23:197–201.
29. Weyer C, Walford RL, Harper IT, Milner M, MacCallum T, Tataranni PA,
Ravussin E: Energy metabolism after 2 y of energy restriction: the
biosphere 2 experiment. Am J Clin Nutr 2000, 72:946–953.
30. Witbracht MG, Laugero KD, Van Loan MD, Adams SH, Keim NL:
Performance on the Iowa gambling task is related to magnitude of
weight loss and salivary cortisol in a diet-induced weight loss intervention
in overweight women. Physiol Behav 2012, 106:291–297.
31. Tomiyama AJ, Mann T, Vinas D, Hunger JM, Dejager J, Taylor SE: Low
calorie dieting increases cortisol. Psychosom Med 2010, 72:357–364.
32. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A,
Proietto J: Long-term persistence of hormonal adaptations to weight
loss. N Engl J Med 2011, 365:1597–1604.
Trexler et al. Journal of the International Society of Sports Nutrition 2014, 11:7 Page 6 of 7
http://www.jissn.com/content/11/1/7

33. Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L,
Heymsfield S, Gallagher D, Mayer L, Murphy E, Leibel RL: Low-dose leptin
reverses skeletal muscle, autonomic, and neuroendocrine adaptations to
maintenance of reduced weight. J Clin Invest 2005, 115:3579–3586.
34. Bryner RW, Ullrich IH, Sauers J, Donley D, Hornsby G, Kolar M, Yeater R: Effects of
resistance vs. aerobic training combined with an 800 calorie liquid diet on
lean body mass and resting metabolic rate. J Am Coll Nutr 1999, 18:115–121.
35. Mettler S, Mitchell N, Tipton KD: Increased protein intake reduces lean
body mass loss during weight loss in athletes. Med Sci Sports Exerc 2010,
42:326–337.
36. Layman DK, Boileau RA, Erickson DJ, Painter JE, Shiue H, Sather C, Christou
DD: A reduced ratio of dietary carbohydrate to protein improves body
composition and blood lipid profiles during weight loss in adult women.
J Nutr 2003, 133:411–417.
37. Bopp MJ, Houston DK, Lenchik L, Easter L, Kritchevsky SB, Nicklas BJ: Lean mass
loss is associated with low protein intake during dietary-induced weight loss
in postmenopausal women. JAmDietAssoc2008, 108:1216–1220.
38. Ravussin E, Burnand B, Schutz Y, Jequier E: Energy expenditure before and
during energy restriction in obese patients. Am J Clin Nutr 1985, 41:753–759.
39. Leibel RL, Rosenbaum M, Hirsch J: Changes in energy expenditure
resulting from altered body weight. N Engl J Med 1995, 332:621–628.
40. Weigle DS: Contribution of decreased body mass to diminished thermic
effect of exercise in reduced-obese men. Int J Obes 1988, 12:567–578.
41. Weigle DS, Brunzell JD: Assessment of energy expenditure in ambulatory
reduced-obese subjects by the techniques of weight stabilization and
exogenous weight replacement. Int J Obes 1990, 14(Suppl 1):69–77.
discussion 77–81.
42. Doucet E, Imbeault P, St-Pierre S, Almeras N, Mauriege P, Despres JP,
Bouchard C, Tremblay A: Greater than predicted decrease in energy
expenditure during exercise after body weight loss in obese men.
Clin Sci 2003, 105:89–95.
43. Rosenbaum M, Vandenborne K, Goldsmith R, Simoneau JA, Heymsfield S,
Joanisse DR, Hirsch J, Murphy E, Matthews D, Segal KR, Leibel RL: Effects of
experimental weight perturbation on skeletal muscle work efficiency in
human subjects. Am J Physiol Regul Integr Comp Physiol 2003, 285:R183–192.
44. Tappy L: Thermic effect of food and sympathetic nervous system activity
in humans. Reprod Nutr Dev 1996, 36:391–397.
45. Ravussin E, Lillioja S, Anderson TE, Christin L, Bogardus C: Determinants of
24-hour energy expenditure in man. Methods and results using a respiratory
chamber. J Clin Invest 1986, 78:1568–1578.
46. Miles CW, Wong NP, Rumpler WV, Conway J: Effect of circadian variation
in energy expenditure, within-subject variation and weight reduction on
thermic effect of food. Eur J Clin Nutr 1993, 47:274–284.
47. Levine JA: Non-exercise activity thermogenesis (NEAT). Best Pract Res Clin
Endocrinol Metab 2002, 16:679–702.
48. Leibel RL, Hirsch J: Diminished energy requirements in reduced-obese
patients. Metabolism 1984, 33:164–170.
49. Jastroch M, Divakaruni AS, Mookerjee S, Treberg JR, Brand MD:
Mitochondrial proton and electron leaks. Essays Biochem 2010, 47:53–67.
50. Rolfe DF, Brand MD: Contribution of mitochondrial proton leak to skeletal
muscle respiration and to standard metabolic rate. Am J Physiol 1996,
271:C1380–1389.
51. Rolfe DF, Brown GC: Cellular energy utilization and molecular origin of
standard metabolic rate in mammals. Physiol Rev 1997, 77:731–758.
52. Rolfe DF, Newman JM, Buckingham JA, Clark MG, Brand MD: Contribution
of mitochondrial proton leak to respiration rate in working skeletal
muscle and liver and to SMR. Am J Physiol 1999, 276:C692–699.
53. Thrush AB, Dent R, McPherson R, Harper ME: Implications of mitochondrial
uncoupling in skeletal muscle in the development and treatment of
obesity. FEBS J 2013, 280:5015–5029.
54. Zurlo F, Larson K, Bogardus C, Ravussin E: Skeletal muscle metabolism is a major
determinant of resting energy expenditure. J Clin Invest 1990, 86:1423–1427.
55. EsterbauerH,OberkoflerH,DallingerG,BrebanD,HellE,KremplerF,PatschW:
Uncoupling protein-3 gene expression: reduced skeletal muscle mRNA in
obese humans during pronounced weight loss. Diabetologia 1999, 42:302–309.
56. Vidal-Puig A, Rosenbaum M, Considine RC, Leibel RL, Dohm GL, Lowell BB:
Effects of obesity and stable weight reduction on UCP2 and UCP3 gene
expression in humans. Obes Res 1999, 7:133–140.
57. Schrauwen P, Xia J, Bogardus C, Pratley RE, Ravussin E: Skeletal muscle
uncoupling protein 3 expression is a determinant of energy expenditure
in Pima Indians. Diabetes 1999, 48:146–149.
58. Harper ME, Dent RM, Bezaire V, Antoniou A, Gauthier A, Monemdjou S,
McPherson R: UCP3 and its putative function: consistencies and
controversies. Biochem Soc Trans 2001, 29:768–773.
59. Cannon B, Nedergaard J: Brown adipose tissue: function and
physiological significance. Physiol Rev 2004, 84:277–359.
60. Rothwell NJ, Stock MJ: Effect of chronic food restriction on energy
balance, thermogenic capacity, and brown-adipose-tissue activity in the
rat. Biosci Rep 1982, 2:543–549.
61. Young JB, Saville E, Rothwell NJ, Stock MJ, Landsberg L: Effect of diet and
cold exposure on norepinephrine turnover in brown adipose tissue of
the rat. J Clin Invest 1982, 69:1061–1071.
62. Harper ME, Brand MD: The quantitative contributions of mitochondrial proton
leak and ATP turnover reactions to the changed respiration rates of hepatocytes
from rats of different thyroid status. JBiolChem1993, 268:14850–14860.
63. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC,
Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR: Identification and
importance of brown adipose tissue in adult humans. N Engl J Med 2009,
360:1509–1517.
64. Valle A, Catala-Niell A, Colom B, Garcia-Palmer FJ, Oliver J, Roca P: Sex-related
differences in energy balance in response to caloric restriction. Am J Physiol
Endocrinol Metab 2005, 289:E15–22.
65. HarperME,DentR,MonemdjouS,BezaireV,VanWyckL,WellsG,KavaslarGN,
Gauthier A, Tesson F, McPherson R: Decreased mitochondrial proton leak and
reduced expression of uncoupling protein 3 in skeletal muscle of obese
diet-resistant women. Diabetes 2002, 51:2459–2466.
66. Chaston TB, Dixon JB, O’Brien PE: Changes in fat-free mass during significant
weight loss: a systematic review. Int J Obes 2007, 31:743–750.
67. Garthe I, Raastad T, Refsnes PE, Koivisto A, Sundgot-Borgen J: Effect of two
different weight-loss rates on body composition and strength and
power-related performance in elite athletes. Int J Sport Nutr Exerc Metab
2011, 21:97–104.
68. American Dietetic A, Dietitians of C, American College of Sports M,
Rodriguez NR, Di Marco NM, Langley S: American College of Sports
Medicine position stand. Nutrition and athletic performance. Med Sci
Sports Exerc 2009, 41:709–731.
69. Burke LM, Loucks AB, Broad N: Energy and carbohydrate for training and
recovery. J Sports Sci 2006, 24:675–685.
70. Paddon-Jones D, Westman E, Mattes RD, Wolfe RR, Astrup A,
Westerterp-Plantenga M: Protein, weight management, and satiety.
Am J Clin Nutr 2008, 87:1558S–1561S.
71. Dirlewanger M, di Vetta V, Guenat E, Battilana P, Seematter G, Schneiter P,
Jequier E, Tappy L: Effects of short-term carbohydrate or fat overfeeding
on energy expenditure and plasma leptin concentrations in healthy
female subjects. Int J Obes Relat Metab Disord 2000, 24:1413–1418.
72. Chin-Chance C, Polonsky KS, Schoeller DA: Twenty-four-hour leptin levels
respond to cumulative short-term energy imbalance and predict
subsequent intake. J Clin Endocrinol Metab 2000, 85:2685–2691.
73. Jenkins AB, Markovic TP, Fleury A, Campbell LV: Carbohydrate intake and
short-term regulation of leptin in humans. Diabetologia 1997, 40:348–351.
74. Dulloo AG, Jacquet J, Girardier L: Poststarvation hyperphagia and body fat
overshooting in humans: a role for feedback signals from lean and fat
tissues. Am J Clin Nutr 1997, 65:717–723.
75. Dulloo AG, Jacquet J, Montani JP: How dieting makes some fatter: from a
perspective of human body composition autoregulation. Proc Nutr Soc
2012, 71:379–389.
76. Jackman MR, Steig A, Higgins JA, Johnson GC, Fleming-Elder BK, Bessesen DH,
MacLean PS: Weight regain after sustained weight reduction is accompanied
by suppressed oxidation of dietary fat and adipocyte hyperplasia.
Am J Physiol Regul Integr Comp Physiol 2008, 294:R1117–1129.
77. Saarni SE, Rissanen A, Sarna S, Koskenvuo M, Kaprio J: Weight cycling of
athletes and subsequent weight gain in middleage. Int J Obes 2006,
30:1639–1644.
doi:10.1186/1550-2783-11-7
Cite this article as: Trexler et al.:Metabolic adaptation to weight loss:
implications for the athlete. Journal of the International Society of Sports
Nutrition 2014 11:7.
Trexler et al. Journal of the International Society of Sports Nutrition 2014, 11:7 Page 7 of 7
http://www.jissn.com/content/11/1/7