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Metabolismo de Nutrientes y Gasto Energético
Metabolismo de Nutrientes y Gasto Energético
Metabolismo de Nutrientes y Gasto Energético
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Kevin D. Hall
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
by Texas Biomedical Research Institute on 04/25/13. For personal use only.
35
NU32CH03-Hall ARI 18 June 2012 11:10
36 Hall
NU32CH03-Hall ARI 18 June 2012 11:10
BODY WEIGHT AND BODY Body fat, protein, and glycogen comprise
COMPOSITION the stored energy of the body, and these stores
must be mobilized when the diet is insufficient
Body weight is an easily measured quantity that
to meet the body’s energy requirements.
has often been the primary variable of interest
Figure 1b illustrates the composition of the
in mathematical models of human energy regu-
body in terms of its energy content, with
lation (4, 12, 13, 56, 66). However, body weight
fat stored in adipose tissue providing the
is less important than body composition when
overwhelming majority of the available stored
it comes to health consequences. Thus, many
energy, especially in obesity. Despite dietary
models of human energy regulation have fo-
carbohydrate providing the majority of the
cused on predicting body composition change
body’s energy demands on a daily basis, glyco-
at some level of detail (1–3, 33, 38, 39, 43, 44,
gen represents a relatively insignificant store of
57, 74, 75, 94, 95, 102, 107).
energy (∼2,000 kcal). Body protein represents
Figure 1a illustrates the body composition
a substantial amount of energy, but in humans
in terms of body fat and fat-free mass in a typ-
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
Figure 1
(a) The chemical composition of an obese 120 kg man (left) differs from that of a lean 70 kg man (right),
primarily as a result of the increased body fat mass. The fat-free mass (FFM) of the body is mostly water,
with a significant contribution of protein and bone mineral. Cellular solids and glycogen make up a very
small part of the chemical composition of the body. (b) Body energy stores are greatly expanded in the obese
man, primarily as a result of the increased body fat mass.
39, 43, 44, 57, 74, 75, 94, 95, 102, 107). A remains relatively unchanged when energy in-
recent model also includes rapid body water take deviates from an energy-balanced diet by
changes as a component of the fat-free mass that an amount EI. In that case, the energy balance
can be important contributors to early weight Equation 1 gives the following equation for
change (44). Only relatively complex compu- the rate of weight change, assuming a constant
tational models have represented the detailed value for ρ:
chemical composition of the body (33, 38).
dBW EI
= . (2)
dt ρ
ENERGY BALANCE
In other words, the rate of weight change is a
Most mathematical models of human energy constant and depends only on the magnitude
regulation make the assumption that weight of the diet change, EI, and the energy den-
change is solely determined by an imbalance sity of the weight change, ρ. With the choice of
between dietary energy intake and the energy ρ = 3,500 kcal/lb, this erroneous equation en-
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
by Texas Biomedical Research Institute on 04/25/13. For personal use only.
expended by the body to maintain life and per- capsulates the static 3,500-Calorie-per-pound
form physical work. The theoretical underpin- rule that has been ubiquitously misused to
ning of this energy balance concept is the first predict weight change (44).
law of thermodynamics, and all energy balance The most serious error of Equation 2 is that
models can be mathematically described by the the energy expenditure rate does not stay con-
following equation: stant but rather dynamically changes. Even the
d earliest mathematical model of human weight
(ρBW ) = EI − EE, (1)
dt change recognized that dynamic changes in en-
where the left side of the equation is the rate ergy expenditure must be taken into account
of change of body energy, with BW being the (4), and it is curious that the persistent erro-
body weight and ρ being an energy density con- neous use of Equation 2 remains so popular to
verting between units of metabolizable energy the present day. The assumption of a constant
and mass. The right side is the energy imbalance ρ = 3,500 kcal/lb is also an oversimplification
between the body’s energy intake rate, EI, and that will be dealt with forthwith.
energy expenditure rate, EE. Any of the terms
in the above equation can depend on time, t, as
well as other parameters. A conceptual repre- Conversion Between Mass
sentation of energy balance models is depicted and Metabolizable Energy
in Figure 2. A simple translation between the energy imbal-
A popular, but erroneous, application of the ance and the rate of weight change, dBW/dt,
energy balance concept involves the assump- occurs only if the energy density of the weight
tion that the energy expended by the body change, ρ, is a constant parameter. However,
as described above, the body is composed of
a variety of chemical constituents with widely
EI BW EE varying energy densities. For example, fat has
an energy density of about 9.4 kcal/g, whereas
Figure 2 protein and carbohydrate have energy densi-
Schematic depiction of the energy balance concept, ties of about 4.7 kcal/g and 4.2 kcal/g, respec-
in which changes in body weight, BW, are assumed tively (64). Other major chemical constituents
to result solely from an imbalance between energy
of the body, water being the most sizable, have
intake, EI, and energy expenditure, EE. Translating
an energy imbalance to a change in weight requires metabolizable energy densities of zero. Thus,
an assumption about the energy density of the translating a given energy imbalance to a rate of
weight change. weight change requires additional assumptions
38 Hall
NU32CH03-Hall ARI 18 June 2012 11:10
account for these early body water changes in Based on assumptions about the chemical com-
terms of both intracellular and extracellular position of lean and fat changes, the energy
fluids. densities have been estimated to be about
Longer-term changes in body fat are accom- ρ L = 1.8 kcal/g and ρ F = 9.4 kcal/g, respec-
panied by changes in lean tissue mass whose me- tively (35). The energy partition ratio, P, ranges
tabolizable energy density is significantly less between 0 and 1 and determines the proportion
than that of body fat (35). To model these of an energy imbalance directed to and from
longer-term body composition changes, Forbes lean versus fat mass. The energy partition con-
(28, 29) hypothesized that the proportion of cept is illustrated in Figure 3.
weight change resulting from lean versus fat The seminal energy partition model of
tissue is a nonlinear function of body fat. The Payne and Dugdale referred to P as the p-ratio,
Forbes hypothesis has since been extended and indicating that this factor determines the pro-
validated implying that ρ is a nonlinear function portion of an energy imbalance accounted for
of the body composition (34, 43, 93). Neverthe- by body protein changes since they ignored the
less, for small changes of weight from an initial contribution of glycogen (74, 75). Payne and
baseline it is valid to approximate the nonlinear Dugdale hypothesized that P was a constant
Forbes curve with a line, and the resulting slope parameter whose value could vary between peo-
gives a value for ρ. For moderately overweight ple and could thereby explain variable interindi-
and obese individuals, the ρ = 3,500 kcal/lb is vidual weight change for equivalent changes of
a reasonable approximation, but this value sig- diet.
nificantly overstates ρ for lean individuals (35). Applying the Forbes hypothesis to the
energy partition model reveals that P is a
nonlinear function of F: P = C/(C+F),
Energy Partition Models where C = 10.4 kg × ρ L /ρ F , as depicted in
To explicitly model body composition change, Figure 4 (11, 34). The initial value of P can
the energy balance Equation 1 can be written be quite diverse for individuals with very differ-
as a pair of equations for the changes in both ent fat mass, in agreement with the Payne and
lean tissue, L, and body fat, F: Dugdale hypothesis. However, the nonlinear-
ity of the Forbes body composition curve sug-
dL gests that P is not a fixed parameter because it
ρL = P(E I − E E)
dt depends continuously on the fat mass, which
. (3)
dF can change considerably with large weight
ρF = (1 − P)(E I − E E) changes.
dt
0.2
MACRONUTRIENT BALANCE
In his early twentieth-century textbook,
0.1 Food and the Principles of Dietetics, Robert
Hutchison (50) compared the human body
to a steam engine, noting that “The building
material of food corresponds to the metal of
0
which the engine is constructed, the energy-
0 25 50 75 100
producers to the fuel which is used to heat
Body fat (kg)
the boiler. Where the body differs from the
Figure 4 engine is that it is able to use part of the
The Forbes hypothesis for the energy partition ratio, P, as a nonlinear function
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
40 Hall
NU32CH03-Hall ARI 18 June 2012 11:10
dF
ρF = FI + εd DNL − KUexcr , (5)
dt FatOx CarbOx ProtOx
− (1 − εk )KTG − FatOx
Figure 6
dP
ρP = PI − GNGp − ProtOx Schematic depiction of the macronutrient balance
dt model, in which changes in body glycogen, G, fat,
where ρ C , ρ F , and ρ P are the energy densities F, and protein, P, are determined by the imbalances
between various macronutrient fluxes (arrows).
of carbohydrate, fat, and protein, respectively.
Contributions of exchange fluxes, such as
The macronutrient intake rates, CI, FI, and PI, gluconeogenesis, GNG, and de novo lipogenesis,
refer to the metabolizable energy intake rates DNL, contribute to imbalances between the intake
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
of dietary carbohydrate, fat, and protein, re- and oxidation rates of carbohydrate, fat, and protein.
by Texas Biomedical Research Institute on 04/25/13. For personal use only.
spectively. The rates of gluconeogenesis from CarbOx, carbohydrate oxidation; CI, carbohydrate
intake; FatOx, fat oxidation; FI, fat intake;
amino acids and glycerol are indicated by GNGp
PI, protein intake; ProtOx, protein oxidation.
and GNGf , respectively. The efficiencies of de
novo lipogenesis, DNL, and ketogenesis, KTG,
are represented by the parameters εd and εk , re- human metabolism to consider all three di-
spectively. When the ketogenic rate increases, etary macronutrients and accurately simulate
ketones are excreted in the urine at the rate the metabolic and body composition changes in
KUexcr . Some flux of carbohydrates is provided response to diet and physical activity changes in
for the production of glycerol 3-phosphate, a wide variety of subject groups.
G3P, which is used in the synthesis of triglyc-
eride. The oxidation rates CarbOx, FatOx, and
ProtOx, sum to the energy expenditure rate, ENERGY EXPENDITURE
EE, less the small amount heat produced via DYNAMICS
flux through ketogenic and de novo lipogenic When diet or physical activities are changed,
pathways. Turnover of glycogen, fat, and the body’s metabolic fuel selection and the en-
protein and the corresponding energy costs are ergy expenditure rate dynamically adapt. All
also included in the model. To account for body mathematical models designed to accurately
water shifts with diets that vary in macronu- predict body weight and composition change
trient as well as sodium content, the model must somehow account for these energy ex-
also tracks intracellular and extracellular fluid penditure dynamics to avoid the same fatal flaw
changes. of the static 3,500-Calorie-per-pound weight
The main model assumptions are that loss rule. Figure 7 depicts the energy expen-
changes of the body’s energy stores are given diture components for examples of relatively
by the sum of metabolic fluxes entering the sedentary lean and obese men. The obese man
pools minus the fluxes exiting the pools. Hence, requires several hundred additional kcal/d to
the computational model obeys the first law maintain his increased weight compared to the
of thermodynamics, and the most recent ver- lean man. Although this general dependence
sion was developed using published human data of weight on energy expenditure may be cap-
from over 50 experimental studies and was val- tured by a simple model of body weight alone,
idated by comparing model predictions with more realistic models of energy expenditure in-
the results of several controlled feeding stud- clude its multiple physiological components:
ies not used for model development (38). To the thermic effect of feeding, resting metabolic
date, this is the only mathematical model of rate, and physical activity.
42 Hall
NU32CH03-Hall ARI 18 June 2012 11:10
The Payne and Dugdale energy partition activity despite obese people typically being
model was the first to discriminate between less active. With weight loss, it costs less energy
“fast” and “slow” lean tissue contributions to perform most physical activities, and there-
to RMR (74, 75). More recently, the com- fore the physical activity expenditure typically
putational model of macronutrient balance decreases unless the quantity or intensity of
(38) incorporated how changes in the sizes of physical activity increases to compensate.
various organs affect RMR, assuming linear All previous mathematical models of human
relationships between changes of fat-free mass energy expenditure include the body weight
and various organ sizes based on cross-sectional effect on physical activity expenditure. Some
data from 110 men and women with body models further subdivide physical activity ex-
mass index (BMI) between 18 and 37 kg/m2 penditure into volitional activities (e.g., exer-
(D. Gallagher, personal communication). Of cise) and low-intensity spontaneous physical
course, longitudinal organ mass changes with activity or nonexercise activity thermogenesis
weight gain and loss need not follow the (38, 94, 95).
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
44 Hall
NU32CH03-Hall ARI 18 June 2012 11:10
was chosen to match changes in overall energy organ sizes were not measured. Conversely,
expenditure measured before and after approx- the computational model of macronutri-
imately stable weight loss (43). When active ent balance that accounts for alterations of
weight loss is followed by subsequent weight energy-requiring metabolic fluxes as well as
stabilization, the change in energy intake organ mass changes required an adaptive
required for the weight loss phase is greater thermogenesis model variable to explain the
than that required for weight stabilization at observed average decrease in both RMR and
the reduced weight. Thus, modeling adaptive total energy expenditure with weight loss (33,
thermogenesis as a function of the energy 38). The adaptive thermogenesis model was
intake change has the natural consequence a linear function of the reduction in energy
of increasing its magnitude in situations of intake below baseline and was used to suppress
active weight loss, in agreement with obser- the metabolic rate of all organs as well as
vations (104). A similar approach was used by reduce the energy expended in spontaneous
Westerterp et al. (107), who added an energy physical activity. The mechanistic basis of such
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
expenditure reduction term to account for the a metabolic adaptation is unclear but may be
by Texas Biomedical Research Institute on 04/25/13. For personal use only.
effect of the degree of energy imbalance on related to reduced sympathetic drive or blunted
metabolic rate. In contrast, the energy partition thyroid activity, possibly as a result of decreased
models of Thomas et al. (94, 95) used a constant circulating leptin (58, 81, 83–85, 103).
parameter to model the metabolic adaptation Interestingly, the adaptive thermogenesis
of RMR with weight loss and did not distin- effect was not required to accurately simulate
guish between active weight loss and weight overfeeding and weight gain in the compu-
stabilization. Kozusko (56, 57) considered a tational model of macronutrient balance (33,
set-point model of adaptive thermogenesis as 38). Similarly, the energy partition models
a function of the body weight itself. of Westerterp et al. (107) and Thomas et al.
Experimental quantification of the adaptive (94, 95) required a metabolic adaptation param-
thermogenesis magnitude depends on the eter to explain changes of energy expenditure
definition of the expected values for RMR with weight loss but not weight gain. If correct,
and total energy expenditure. Typically, such an asymmetry in energy regulation
cross-sectional regression equations are used suggests that the body is neutral to overfeeding
to calculate the expected values, using for RMR and weight gain but actively resists weight
and total energy expenditure measurements loss by improving its energy efficiency during
derived either from baseline body composition underfeeding—much to the dismay of over-
data in the same subjects (46, 60, 80) or from weight and obese people wishing to lose weight.
a separate group of similar subjects (18, 19).
But such expected values for RMR and energy
expenditure ignore the possible changes in INSIGHTS OBTAINED FROM
organ size distribution as well as changes in MATHEMATICAL MODELS
fluxes through energy-requiring metabolic
Is a Calorie a Calorie? The Effect
pathways during over- or underfeeding
of Dietary Macronutrients
(described above). Whether such consider-
on Body Composition
ations can explain the observed changes in
energy efficiency is unclear. A topic of great popular interest is the rela-
Novotny & Rumpler (72) used a mathe- tive effectiveness of weight loss diets varying
matical model to investigate the impact of a in macronutrient composition (92). While fully
disproportionate reduction of high-metabolic- complying with the laws of thermodynamics,
rate organs during weight loss and found macronutrient balance models allow for the
that such changes could potentially explain possibility that body weight may depend on
the observed reduction of RMR, but the the diet composition because the energy stored
per unit mass of carbohydrate, fat, and protein Another argument against the concept that
varies considerably, especially when account- “a calorie is a calorie” is that the diet com-
ing for the intracellular water associated with position can have a significant impact on the
stored glycogen and protein. Furthermore, di- flux pattern through various energy-requiring
etary carbohydrates have an impact on renal metabolic pathways and may thereby affect
sodium excretion via insulin (16), which re- the body’s energy expenditure rate (23, 24).
sults in concomitant changes in extracellular Despite the attractive theoretical possibility of
fluid volume. Therefore, when the composi- a significant “metabolic advantage” of one diet
tion of the diet is altered, transient changes over another, simulations using a computa-
in macronutrient stores and body fluid shifts tional model that includes the contributions
will result in an expected body weight change of energy-requiring metabolic fluxes (38) sug-
even when the energy content of the diet is held gest that the overall effect of diet composition
constant (99). on energy expenditure appears to be relatively
A more important consideration is whether modest, especially when dietary protein is un-
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
body fat mass depends on the macronutrient changed. Specifically, the model predicts that
by Texas Biomedical Research Institute on 04/25/13. For personal use only.
composition of the diet. Proponents of low- large isocaloric exchanges of dietary carbohy-
carbohydrate diets for weight loss emphasize drate and fat will result in energy expenditure
the ability of dietary carbohydrate to influ- changes of around 100 kcal/d. These model re-
ence adipose tissue fat storage via circulating sults agree with experimental observations (86),
insulin (92). Therefore, it is claimed that and therefore the assumption that a “calorie is a
body fat changes depend primarily on dietary calorie” may be a reasonable first approximation
carbohydrate and not the energy content of over relatively short time periods. However,
the diet. Macronutrient balance models allow even small differences in energy expenditure
for this possibility, but energy balance and and macronutrient balance can theoretically
energy partition models assume that “a calorie lead to significant differences of body weight
is a calorie” (8) and therefore all equivalently and composition if the diets are maintained over
reduced energy diets should lead to identical long periods. A 100 kcal/d difference in energy
body fat loss regardless of their macronutrient expenditure alone could lead to an initial body
composition. However, this assumption is fat imbalance of about 10 g/d. Using current
not an obvious or necessary consequence of body composition methods, it would require a
the first law of thermodynamics because the sustained period of about 100 days to detect
more general macronutrient balance models such a difference in body fat. Nevertheless, this
allow for an effect of diet composition while possibility requires further investigation.
also obeying the law of energy conservation.
In fact, to achieve an independence of body
fat on the macronutrient content of the diet Behavioral Adaptations
requires a robust physiological control system to Energy Imbalance
to precisely adapt metabolic fuel selection to Energy imbalance and weight change can
the diet composition (37). Nevertheless, most influence behaviors that directly affect energy
inpatient studies with adequately controlled intake and/or expenditure. For example,
diets have shown little impact of diet composi- outpatient weight loss interventions geared
tion on body weight and fat mass changes (55, to reducing energy intake typically result in a
59, 100, 105, 111, 112), but there are notable period of weight loss that plateaus after about
exceptions (52, 77, 78). Thus, it remains to be six to eight months, followed by slow weight
determined whether the physiology regulating regain (47, 90). The well-known deficiencies
metabolic fuel selection can fully adapt to in assessing free-living energy intake (97, 109)
diet composition over extended time periods make it extraordinarily difficult to interpret
without resulting in body fat mass changes. such results, and mathematical models have
46 Hall
NU32CH03-Hall ARI 18 June 2012 11:10
recently been proposed to address this difficulty and a corresponding reduction in subsequent
by estimating changes of free-living energy spontaneous physical activity. Hence, appli-
intake using longitudinal measurements of cation of the model of Thomas et al. requires
body weight (38, 40, 96). Such models have a priori knowledge of the highly variable
shown that the typical weight loss, plateau, and response characteristics of the individual.
regain trajectory was likely due to short-lived The highly variable behavioral adaptations
adherence to the prescribed diet that was pro- to energy imbalance pose a significant challenge
gressively relaxed over the first year to return for modeling individual weight changes. Rather
to the preintervention level (38, 44). Thus, an than attempting to directly simulate these be-
energy imbalance resulting in transient weight havior changes, models that start by assum-
loss leads to an eventual adaptation of behavior ing no effect might be used to help estimate
to return to the original lifestyle. the magnitude of any behavioral adaptations by
Another example of a behavioral adapta- measuring the difference between the measured
tion to energy imbalance is the compensatory and model-predicted weight change. Further-
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
changes in energy intake when a physical ac- more, models that can quantitatively integrate
by Texas Biomedical Research Institute on 04/25/13. For personal use only.
tivity program is added. In particular, engaging physiological data collected during the inter-
in many weeks of supervised exercise leads to a vention may be used to better characterize be-
wide range of individual weight changes, with havioral adaptations in the overall context of
some people gaining weight and others having energy and macronutrient balance.
greater-than-expected weight loss (7, 10, 53,
54). These results imply that volitional phys-
ical activity can have a wide range of effects on Weight Change Variability
energy intake and/or other components of total Due to the Uncertainty in Baseline
energy expenditure. Energy Requirements
Under- and overfeeding may also signifi- Calculating the energy imbalance generated
cantly influence physical activity expenditure, by a given diet requires knowing the energy
especially nonvolitional spontaneous physical requirement to maintain the baseline body
activity (62, 63). This effect is very difficult weight. Unfortunately, even the specialized
to model because of the highly variable in- and expensive doubly labeled water method
terindividual response. Thomas et al. (94, 95) cannot measure the initial energy requirements
attempted to account for the average change in of a free-living individual with a precision
spontaneous physical activity in the presence better than ∼5% (87). The uncertainty of the
of this variability. However, the mathematical baseline energy requirements translates to an
equation used to model this effect has two expected interindividual variability of weight
constraints on its use. First, the model is change even if adherence to a prescribed diet
not applicable during prolonged substantial is perfect (44). This is a fundamental limitation
underfeeding because the equation allows for on a model’s ability to precisely predict the
the possibility of negative values for the spon- body weight time course of an individual.
taneous physical activity expenditure that is For example, assuming a ± 150 kcal/d un-
not physiological. Second, the model requires certainty in the initial energy expenditure
that changes in any other component of total requirements, the dotted curves in Figure 8a
energy expenditure are positively correlated to illustrate the minimum expected weight gain
changes in spontaneous physical activity. For variability during a study intending to over-
example, increased volitional physical activity feed subjects by 500 kcal/d above baseline
or exercise in the Thomas model necessarily energy requirements. In this example, the
results in an increased spontaneous physical energy partition model of Hall et al. (44)
activity. Such an effect would not apply to was used to simulate multiple runs of the
people where added exercise results in fatigue same 70-kg “virtual study subject,” assuming
Initial BW = 120 kg
30 initial body fat have a greater fraction of their
Weight gain (kg)
48 Hall
NU32CH03-Hall ARI 18 June 2012 11:10
added to all individuals across BMI categories, the anatomical location of body fat, especially
then mathematical models predict that more in visceral adipose tissue, has profound clinical
weight would be gained in people with larger importance, and mathematical models have
BMIs, thereby pushing out the upper tail of the only just begun to capture the relationship be-
BMI distribution with time. Whether this ef- tween body fat changes in various depots during
fect is sufficient to explain the evolving shape of weight loss and gain (42, 45). Furthermore,
the BMI distribution is an intriguing question. even the most detailed computational models of
macronutrient metabolism implicitly represent
the effect of hormones such as insulin, but an
CONCLUSIONS AND FUTURE explicit representation of organ systems along
DIRECTIONS with concentrations of hormones and metabo-
In the physical sciences, there is a long history lites would be desirable—especially on shorter
of developing mathematical models that quan- time scales so that the response to individual
titatively describe past data and predict the re- meals could be simulated (17, 73). Conversely,
Annu. Rev. Nutr. 2012.32:35-54. Downloaded from www.annualreviews.org
sults of key new experiments. Such quantitative capturing the dynamics of energy regulation
by Texas Biomedical Research Institute on 04/25/13. For personal use only.
models have been relatively rare in the biomedi- and body composition change during aging as
cal sciences, possibly because biological systems well as during childhood and adolescent growth
are highly complex, and defining the important (9) will require extending current mathematical
variables is often difficult. Fortunately, models models to operate on much longer time scales.
of human energy regulation and macronutri- An editorial describing the future of
ent metabolism are constrained by conservation biomedical research remarked that “formula-
principles and knowledge of the main metabolic tion of a mathematical model is the ultimate
pathways that contribute to whole-body test of understanding . . . If the model repro-
imbalances. duces the behavior of the system under a range
A guiding principle when developing a of conditions and predicts the consequences
mathematical model is to target its complex- of . . . modifications in any component, one can
ity to the class of phenomena that the model be relatively confident about understanding
is intended to address. Mathematical models of the system” (76). As highlighted in this review,
human energy regulation and body weight dy- much progress has been made on integrat-
namics have ranged in complexity from detailed ing past research on human nutrition and
computational models that accurately simulate metabolism into self-consistent and predictive
dynamic changes in macronutrient metabolism mathematical models of energy regulation and
and body composition to overly simplified static body composition change. Such models can
weight loss models that fail to capture the most highlight knowledge gaps, integrate metabolic
basic features of body weight dynamics. Most data within a broader context of knowledge,
other models fall between these extremes and and make testable predictions, thereby helping
have been used to provide important insights design new experiments. Indeed, the best
regarding human energy regulation and body mathematical models will never replace exper-
weight change. imental research but rather will be used to help
Despite significant progress, much work re- design the key experiments that, in turn, will
mains for improving and expanding the existing help improve the mathematical models and our
mathematical models of human energy regu- understanding of the human energy regulation
lation and body weight change. For example, system.
DISCLOSURE STATEMENT
The author is not aware of any affiliations, memberships, funding, or financial holdings that might
be perceived as affecting the objectivity of this review.
ACKNOWLEDGMENTS
The author thanks Caron C. Chow for his critical reading of the manuscript and the suggested
improvements. The author’s research was supported by the Intramural Research Program of the
NIH, National Institute of Diabetes and Digestive and Kidney Diseases.
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Nutrition
Contents Volume 32, 2012
v
NU32-FrontMatter ARI 26 June 2012 13:26
Indexes
Errata
vi Contents