![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
3 Institut Pluridisciplinaire Hubert Curien, Département Ecologie Physiologie Ethologie, UMR 7178 CNRS/ULP, associé à l'Université Henri Poincaré, Nancy 1 67087 Strasbourg, cedex 2 France and 4 Biochemistry Department, Memorial University, St. John's, Newfoundland A1B 3X9, Canada
* To whom correspondence should be addressed. E-mail: jean-patrice.robin{at}c-strasbourg.fr.
 |
ABSTRACT |
|---|
 TOP ABSTRACT IntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
|
Introduction |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
80–90% of the lipid reserves have been used, protein catabolism increases dramatically (P3 of starvation) (4,8,9,15). During P3, fat stores fall below a lower defended level. Animals in this metabolic situation increase their exploratory activity to search for food (4,8) and we hypothesize that the dynamics of body store recovery depends on whether refeeding is initiated before or after the lipid threshold is reached. The aim of this study was to determine the effect of the metabolic status reached during starvation on the kinetics of recovery of body stores, particularly during early refeeding. Rats were refed in P2 or in P3 of starvation. Changes in energy intake and body composition were determined until the prestarvation body mass was recovered.
|
Materials and Methods |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
Experimental procedures. Rats were randomly assigned to experimental groups. Body mass and age ranged from 410 ± 1 g to 412 ± 1 g and from 15.2 ± 0.1 wk to 15.5 ± 0.2 wk, respectively, and did not differ among the groups. Experimental groups consisted of a fed control group, 3 groups that were starved for 5 d up to the middle of P2 (P2 groups)5, and 4 groups that were starved until they had been in P3 for 2 d, i.e. starving for a total duration of 11–12 d (P3 groups). The criteria used to stop starvation of the P3 groups were: body mass loss (>30%), increased daytime locomotor activity, piloerection, and 2 consecutive days of an increased rate of body mass loss. From previous experiments, rats starved up to the early stages of P3 are capable of restoring their body condition (7,9). Two groups of rats that were not refed [P2R0 (rats starved up to P2 and not refed) and P3R0 (rats starved up to P3 and not refed)] were killed by decapitation between 9 and 11 h. The remaining rats were refed and killed similarly after 3 d [P2R3 (rats starved up to P2 and refed for 3 d) and P3R3 (rats starved up to P3 and refed for 3 d) groups], 7 d [P3R7 (rats starved up to P3 and refed for 7 d) group], or once the initial body mass was recovered [P2RT (rats starved up to P2 and refed up to the initial body mass recovery) and P3RT (rats starved up to P3 and refed up to the initial body mass recovery) groups]. The latter 2 groups were included to determine the impact of metabolic state at refeeding on the deficit in lipid stores. Duration of starvation or refeeding and body composition were not affected by age. Body mass loss during starvation did not differ among P2 groups or among P3 groups.
Blood was collected in heparinized tubes and centrifuged at +4°C for 3000 x g; 10 min. The liver, the retroperitoneal (RP) and epididymal (EPI) fat pads, the intestine, the stomach, and leg muscles [soleus and extensor digitorum longus (EDL)] were dissected and weighed (±0.001 g). The intestine and the stomach were cleared of their contents. The fat pads, intestines, and stomach were replaced with the remaining carcass. The liver, muscles, carcass, and plasma were kept frozen (–20°C) until analysis.
Analytical methods. The carcass was ground roughly under liquid nitrogen. The muscles, the liver, and 100 g of the carcass were freeze-dried until constant mass was achieved. The dry aliquots of carcass and the liver were then finely ground to obtain a homogenous powder. Total lipids were determined on the carcass and on the liver (16). The Test-Combination 240 052 (Boerhinger) was used to determine the triacylglycerol content of carcasses. Nitrogen content was measured in the muscles, carcass, and liver using the Kjeldahl method. Proteins were calculated as 6.25·nitrogen (9). Plasma nonesterified fatty acids (NEFA) and β-hydroxybutyrate concentrations were measured using the NEFA C test (Wako Chemicals) and an enzymatic Test-Combination (Boehringer-Mannheim), respectively.
Calculations and statistics. The specific daily change in body mass (dm/mdt) was the difference in body mass between 2 consecutive days divided by mean body mass for the 2 d. Net body mass was the body mass minus digestive contents. Total body water was net body mass minus the dry mass of the carcass, liver, and dissected muscles. Structural lipids were calculated as the body fat minus body triacylglycerols. The increase in body components during the acclimation period in control-fed rats was estimated assuming that the contribution of water, proteins, and lipids to body mass was constant. In control and refed rats, an endogenous lipid production corresponding to the synthesis of lipid from the animal body was calculated when the intake could not account for the storage.
Energy expenditure or gain calculations between groups followed the procedure of Hill et al. (17,18). The individual losses during starvation were calculated by subtracting the mass of body components in individual rats of the P2R0 and P3R0 groups from the mean masses in the prestarvation group. The body component gains during the refeeding period (R0 to RT, R0 to R3, R3 to R7 or RT, and R7 to RT) were obtained similarly. Energy intake was calculated from food intake and its metabolizable energy content. The amount of food in the digestive tract in R3 rats was subtracted from the energy intake during the first 3 d of refeeding, because R0 rats had no food in the digestive tract. According to Hill et al. (17,18), the ingested metabolizable energy was calculated as the sum of: 1) energy stored in the animal; 2) cost of accumulation of energy reserves (0.36 kJ to store 1 kJ of fat and 1.25 kJ to store 1 kJ of protein); and 3) energy required for maintenance (e.g. locomotion, thermoregulation, and metabolic events). The energy stored during refeeding was calculated as the gain in lipid and protein mass multiplied by their energetic equivalent (39.3 and 18.0 kJ·g–1, respectively) (9). The negligible energy stored as carbohydrates (11,19) was not determined. Daily energy expenditure was daily energy intake minus daily energy storage (ES). Energy efficiency (%) was: stored energy/energy intake x 100 (20).
Results are presented as means ± SEM. Data were analyzed by using Sigmastat 3.0 software. Arcsin transformations were performed on percentages before statistical analysis. Nonparametric tests were used when normality or homoscedacity failed. A Student's t test was used to compare the ratio duration of fasting:duration of refeeding. In each group of rats, lipid intake and storage was compared by using paired t tests (except in P3R3 rats where a nonparametric Wilcoxon's test on rank was used). One-way ANOVA followed by Student-Newman-Keuls tests for multiple group comparisons were used to compare age, body mass, body mass loss, energy intake, whole body composition, liver composition, body component gains, organ masses (except for RP fat masses), energy expenditure and efficiency, and time of food deprivation between the different groups. Within groups, dm/mdt values and energy intakes were compared by the use of ANOVA for repeated measures. The relationship between body composition, time of food deprivation, time of refeeding, and age was analyzed through regression lines. A nonparametric Kruskal-Wallis test followed by Dunn's test for multiple group comparisons was used to compare plasma metabolites, triacylglycerol:total lipid mass ratio, water:protein ratio of the body mass gain (W:Pgains) or for body reserves (W:Preserves) and RP fat masses. Differences were considered significant at P < 0.05.
|
Results |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
Changes in body mass. The rats recovered the body mass lost during starvation within 6.7 ± 0.3 d and 11.5 ± 0.4 d of refeeding in P2 and P3 rats, respectively. The duration of refeeding:duration of starvation ratio in P3 refed rats (1.07 ± 0.05) was lower than in P2 rats (1.34 ± 0.06; P < 0.003).
Energy intake. Considering total energy intake, P3 refed rats consumed less total energy compared with P2 rats during the first 48 h (P < 0.05), but the specific energy intake (i.e. per unit body mass) did not differ during this period (Supplemental Fig. 1). In P2 rats, the specific energy intake remained constant during refeeding and was higher than in control-fed rats (P < 0.05). In P3 rats, it increased after 48 h of refeeding (P < 0.025). Maximum energy intake in P3 refed rats was higher than during the fed period (P < 0.001) and than in P2 refed rats (P < 0.002). P3RT rats were still hyperphagic at body mass recovery (P < 0.01; Supplemental Fig. 1).
Energy expenditure and energy efficiency. The energy expenditure for maintenance (EEM), ES, and the energy cost of storage in control rats accounted for 85 ± 2%, 8 ± 1%, and 7 ± 1% of the ingested metabolizable energy, respectively. EEM values did not differ between P2 refed and control rats. ES values in P2RT rats were only elevated compared with those of control and P2R3 rats (P < 0.01). In P3 refed rats, EEM values were lower than in control rats and P2 refed rats (P < 0.05) (Supplemental Fig. 2). In P3R7 and P3RT refed rats, ES was higher (P < 0.05) than in control rats. In P3RT rats, values were greater (P < 0.05) than in P3R3 and P2RT rats. Energy cost of storage was higher (P < 0.05) than in control rats for refeeding durations longer than 3 d (Supplemental Fig. 2). Energy efficiency values in P3 refed (25.4 ± 4.4 to 37.7 ± 4.1%) and P2RT rats (24.5 ± 4.6%) were higher than in control (8.4 ± 0.9%) and P2R3 rats (12.4 ± 2.9%) (P < 0.01). In P3RT rats, energy efficiency was 51% higher than in P2RT and P3R3 rats (P < 0.02).
Overall changes in body fat, protein, and water masses during starvation and refeeding. Body lipid mass in P3R0 rats was lower compared with P2R0 rats (P < 0.05; Table 1). The ratio of triacylglycerol:total lipid mass decreased during starvation (P < 0.02), a consequence of a slower net catabolism of structural lipids. At body mass recovery, total body fat remained lower in refed than in control rats (P < 0.05) as a result of a deficit in body triacylglycerol mass, structural lipids having been fully restored (Table 1).
|
Rate of recovery of body components. The daily gains in body and water masses during recovery were greatest during early refeeding and were significantly higher in P3 than in P2 rats (Supplemental Fig. 3). Water accounted for three-quarters of the body mass gain in R3 rats, but its fraction of weight gain was lower in the other groups of refed rats (P < 0.05). The W:Pgains (21.6 ± 2.5) in P3R3 rats was higher than in P2R3 rats (6.1 ± 0.5; P < 0.001). W:Pgains in R3 refed rats were higher than the W:Preserves in control rats (3.2 ± 0.1; P < 0.001). Later during refeeding, W:Pgains were similar to W:Preserves in control rats.
The daily protein gain was lower in P3R3 rats than in P2R3 rats (P < 0.05), opposite of the daily body lipid gain (Supplemental Fig. 3). Later in the refeeding period, daily gains for lipid and protein tended to increase in P2 and P3 rats (Supplemental Fig. 3). Protein gains became higher in P3 rats than in P2-RT rats (P < 0.05; Supplemental Fig. 3), whereas lipid gains no longer differed. In control and P2 rats, lipid storage was not significantly greater than intake (Table 2). However, P3 refed rats had endogenous lipid production (P < 0.05; Table 2). In P2R3 rats, three-quarters of the stored lipids were structural, whereas they accounted for less than one-sixth in other groups (calculated from Table 1). Ingested protein accounted for 200 to 800% of the storage in all groups of rats.
|
Proteins in the EDL were catabolized (P < 0.05) in P2R0 and P3R0 rats, but in the soleus, catabolism occurred in only P3R0 rats (P < 0.05; Supplemental Table 1). After 3 d of refeeding, protein lost from EDL in P2 rats was restored, whereas no significant amount of protein was regained in the muscles of P3 rats. In P3RT rats, the protein mass in both muscles was restored, soleus protein being higher than in control rats (P < 0.05; Supplemental Table 1). The water ratio of both muscles was unchanged throughout the period of food deprivation.
The decreased liver mass during starvation was recovered within 3 d of refeeding (Supplemental Table 2). In P3R3 rats, the liver:body mass ratio was higher than in control fed rats (P < 0.05). Total lipid, protein, and water masses decreased during starvation in P2 and P3 rats (P < 0.05). Liver composition was normalized within 3 d except for protein, which was restored in P3 rats after 7 d (Supplemental Table 2). In P2R3 and P3R3 rats, 20 and 45%, respectively, of total body stored protein was deposited in the liver, despite liver protein accounting for <3.5% of total protein mass (calculated from Table 1 and Supplemental Table 2). In P2R3 rats that had not restored large amounts of lipid at the whole body level, gains in liver lipid accounted for 17% of total stored lipids, whereas liver lipid represented 2% of total lipid mass (calculated from Table 1 and Supplemental Table 2). After d 3 of refeeding, the liver contribution to the various body component gains became negligible.
|
Discussion |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
In early refeeding, the restoration of lipid and protein stores followed different patterns depending on the phase of starvation reached. In P3 rats, recovery is not consistent with the concept of a deficit in body lipid accretion after total food deprivation (9,10,13,20). In P2 rats, the daily lipid accretion was low and similar to the rate in fed rats, whereas in P3 rats, this was the case for protein. It is unlikely that a limitation in lipid or protein intake occurs in P2 or P3 rats, respectively, because intake was higher than storage. In starved nonobese animals, survival is limited by triacylglycerol availability (19). Furthermore, at the start of P3 of starvation, a lower threshold in the lipid level is attained (4,8). In rats of this body mass (9), the threshold triacylglycerol mass (7–8 g) is intermediate between the level in P3 and P2 rats. The metabolism of P3 rats seems then to be directed toward triacylglycerol storage to rapidly increase its mass above the lower threshold. This is achieved at the expense of an energetically costly endogenous lipid production (27), emphasizing the necessity to rapidly increase triacylglycerol stores above the threshold level. This is supported by self-choice diet experiments in which lipid intake is higher in P3 than in P2 rats in early refeeding (28). In contrast, the driving force to restore proteins is less obvious (28). Several hypotheses may explain such a metabolic orientation in P3 refed rats. First, the high rate of fat deposition in restricted refed rats is partly under corticosteroid control (29) and yet P2 and P3 of starvation are characterized by low and high corticosterone plasma concentrations, respectively (9,19). This hormonal pattern would favor fat deposition in P3 refed rats, in contrast to P2 refed rats. Second, hypometabolism during restricted feeding persists during refeeding, the saved energy being preferentially directed toward lipid storage (12,30). Accordingly, EEM was significantly lower in P3 than in P2 rats in early refeeding.
During energy restriction, fat pad and muscle mass decreases show different responses (13,14,19,20). Their restoration in early refeeding corresponded to some extent to their sensitivity to food deprivation (Supplemental Table 1). For example, P3 refed rats first stored lipids at the whole body level, but only the fat pad most sensitive to starvation increased in mass. The same was true for protein and muscle mass in P2 refed rats. However, the extent of the fuel storage at the whole body level modulates the extent of restoration in individual tissues. When protein is low (P3 rats), muscle masses do not increase regardless of their sensitivity to starvation. The same applies in P2 rats for lipid storage and fat pad masses.
After the first days of refeeding, EEM differences between groups persisted, but the kinetics of body fuel restoration became more similar. However, when body protein was restored, a deficit in body fat remained that, for individual fat deposits, was independent of its previous response to starvation. In starved-refed rats, lipid restoration is slower than for protein regardless the duration of starvation in P2 (9,10,13) or the state of starvation at refeeding (this study). Thus, as indicated by P-ratios, prolonged starved- and restricted-refed rats have different overall patterns of body reserve restoration (Supplemental Fig. 4). This occurs despite persistent hypometabolism in P3 refed rats.
Body reserve restoration occurs through a combination of hyperphagia and hypometabolism, the contribution of the former being the highest in P2 refed rats (17,31; this study). In P3 refed rats, the same situation occurs; the effect of hypometabolism alone could account for 1.4–2.0 times the actual recovery. Similarly, hyperphagia alone can account for 2.0–4.0 times the actual gain and appears to play the major role (approximately two-thirds of the gain) in the recovery of body reserves. Nevertheless, hypometabolism during refeeding prolongs the energy-saving processes established during starvation. Furthermore, during restricted refeeding, EEM may be adjusted (reduced up to 40–50%) to maintain body reserves at a constant level (17,18). Remarkably, the same occurs in refed P3 rats, because EEM values were similar in hyperphagic (400 g body mass) (this study) and restricted refed rats (250 g body mass) (17,18). This suggests that energy expenditure in such extreme situations is matched to the minimum required to maximize body reserve recovery or conservation, as is exemplified by the high food efficiency we found.
To conclude, despite the fact that P3 rats exhibited a more severe degradation of the digestive mucosa than P2 rats (24), were more dehydrated, starved for a longer duration, and reached threshold amounts of body fuels (this study), they are not disadvantaged during the restoration of body reserves. This provides additional evidence against the previous theory that P3 is a premortal state leading to a final, irreversible degeneration of the cells (7,9 for review). Instead, these findings support the concept of P3 being a highly adaptive metabolic situation and provide a physiological basis for the concept of the signal for refeeding (2,4,8) operating at the P2/P3 transition. However, our data demonstrate that the depletion of lipid stores below a lower threshold influences the restoration pattern of body reserves. Further studies should be carried out to determine the influence of the composition of the diet on the kinetics of the recovery of protein and lipid in animals refed in P2 or P3 of starvation.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
2 Supplemental Tables 1and 2 and Supplemental Figures 1–4 are available with the online posting of this paper at jn.nutrition.org.
5 Abbreviations used: dm/mdt, mass specific daily change in body mass; EDL, extensor digitorum longus; EEM, energy expenditure for maintenance; EPI, epididymal adipose tissue; ES, energy storage; NEFA, nonesterified fatty acid; P2, phase II; P3, phase III; P2R0, rats starved up to phase II and not refed; P2R3, rats starved up to phase II and refed for 3 d; P2RT, rats starved up to phase II and refed up to the initial body mass recovery; P3R0, rats starved up to phase III and not refed; P3R3, rats starved up to phase III and refed for 3 d; P3R7, rats starved up to phase III and refed for 7 d; P3RT, rats starved up to phase III and refed up to the initial body mass recovery; RP, retroperitoneal adipose tissue; W:Preserves, water:protein ratio for body reserves; W:Pgains: water:protein ratio of the body mass gain.
Manuscript received 3 May 2007. Initial review completed 22 May 2007. Revision accepted 20 February 2008.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
|---|
1. Finn PF, Dice JF. Proteolytic and lipolytic responses to starvation. Nutrition. 2006;22:830–44.[Medline]
2. Wang T, Hung CCY, Randall DJ. The comparative physiology of food deprivation: from feast to famine. Annu Rev Physiol. 2006;68:223–51.[Medline]
3. Blackburn GL, Flatt JP, Clowes GHA, O'Donnell TF, Hensle TE. Protein sparing therapy during periods of starvation with sepsis or trauma. Ann Surg. 1973;177:588–94.[Medline]
4. Cherel Y, Groscolas R. Relationships between nutrient storage and nutrient utilisation in long-term fasting birds and mammals. In: Adams NJ, Slotow RH, editors. Proceedings of the 22nd International Ornithological Congress, Durban, (South Africa): BirdLife South Africa, Johannesburg; 1999. p. 17–34.
5. Kotler DP, Tierney AR, Francisco A, Wang J, Pierson RN Jr. The magnitude of body cell mass depletion determines the timing of death from wasting in AIDS. Am J Clin Nutr. 1989;50:444–7.
6. Rössner S. Starvation as a creative force. Obes Res. 1996;4:183–7.[Medline]
7. Cherel Y, Le Maho Y. Refeeding after the late increase in nitrogen excretion during prolonged fasting in the rat. Physiol Behav. 1991;50:345–9.[Medline]
8. Groscolas R, Robin JP. Long term fasting and re-feeding in penguins. Comp Biochem Physiol A. 2001;128:645–55.[Medline]
9. Belkhou R, Cherel Y, Heitz A, Robin JP, Le Maho Y. Energy contribution of proteins and lipids during prolonged fasting in the rat. Nutr Res. 1991;11:365–74.
10. Harris RBS, Kasser TR, Martin RJ. Dynamics of recovery of body composition after overfeeding, food restriction or starvation of mature female rats. J Nutr. 1986;116:2536–46.
11. Dulloo AG, Girardier L. Adaptive changes in energy expenditure during refeeding following low-calorie intake: evidence for a specific metabolic component favoring fat storage. Am J Clin Nutr. 1990;52:415–20.
12. Dulloo AG. Human pattern of food intake and fuel-partitioning during weight recovery after starvation: a theory of autoregulation of body composition. Proc Nutr Soc. 1997;56:25–40.[Medline]
13. Yang MU, Presta E, Bjorntorp P. Refeeding after fasting in rats: effects of duration of starvation and refeeding on food efficiency in diet-induced obesity. Am J Clin Nutr. 1990;51:970–8.
14. Goodman MN, Ruderman NB. Starvation in the rat. I. Effect of the age and obesity on organ weights, RNA, DNA, and protein. Am J Physiol Endocrinol Metab. 1980;239:269–76.
15. Jackson JM, Blaine D, Powell-Tuck J, Korbonits M, Carey A, Chir B, Elia M. Macro-and micronutrient losses and nutritional status resulting from 44 days of total fasting in a non-obese man. Nutrition. 2006;22:889–97.[Medline]
16. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem. 1957;226:497–509.
17. Hill JO, Fried SK, DiGirolamo M. Effects of fasting and restricted refeeding on utilization of ingested energy in rats. Am J Physiol Regul Integr Comp Physiol. 1984;247:318–27.
18. Hill JO, Latiff A, DiGirolamo M. Effects of variable caloric restriction on utilization of ingested energy in rats. Am J Physiol Regul Integr Comp Physiol. 1985;248:549–59.
19. Cherel Y, Robin JP, Heitz A, Calgari C, Le Maho Y. Relationships between lipid availability and protein utilization during prolonged fasting. J Comp Physiol B. 1992;162:305–13.[Medline]
20. Bjorntorp P, Yang MU. Refeeding after fasting in the rat: effects on body composition and food efficiency. Am J Clin Nutr. 1982;36:444–9.
21. Hamilton CL. Problems of refeeding after starvation in the rat. Ann N Y Acad Sci. 1969;157:1004–17.[Medline]
22. Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci. 1953;140:578–96.[Medline]
23. Fried SK, Hill JO, Nickel M, DiGirolamo M. Prolonged effects of fasting-refeeding on rat adipose tissue lipoprotein lipase activity: influence of caloric restriction during refeeding. J Nutr. 1983;113:1861–9.
24. Dunel-Erb S, Chevalier C, Laurent P, Bach A, Decrock F, Le Maho Y. Restoration of the jejunal mucosa in rats refed after prolonged fasting. Comp Biochem Physiol A. 2001;129:933–47.[Medline]
25. Bjorntorp P, Edstrom S, Kral JG, Lundholm K, Presta E, Walks D, Yang MU. Refeeding after fasting in the rat: energy substrate fluxes and replenishment of energy stores. Am J Clin Nutr. 1982;36:450–6.
26. Schemmel R, Mickelsen O, Tolgay Z. Dietary obesity in rats: influence of diet, weight, age, and sex on body composition. Am J Physiol. 1969;216:373–9.
27. Flatt JP. Energy costs of ATP synthesis. In: Kinney JM, Tucker HN, editors. Energy metabolism: tissue determinants and cellular corollaries. New York: Raven Press; 1992. p. 319–43.
28. Thouzeau C, Le Maho Y, Larue-Achagiotis C. Refeeding in fasted rats: dietary self-selection according to metabolic status. Physiol Behav. 1995;58:1051–8.[Medline]
29. Dulloo AG, Seydoux J, Girardier L. Role of corticosterone in adaptive changes in energy expenditure during refeeding after low calorie intake. Am J Physiol Endocrinol Metab. 1990;259:658–64.
30. Dulloo AG, Girardier L. Adaptive role of energy expenditure in modulating body fat and protein deposition during catch-up growth after early undernutrition. Am J Clin Nutr. 1993;58:614–21.
31. Penicaud L, Le Magnen J. Recovery of body weight following starvation or food restriction in rats. Neurosci Biobehav Rev. 1980;4:47–52.[Medline]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
