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Resistance to lean mass gain in constitutional thinness in free-living conditions is not overpassed by overfeeding.

ABSTRACT: BACKGROUND:Constitutional thinness (CT), a non-malnourished underweight state with no eating disorders, is characterized by weight gain resistance to high fat diet. Data issued from muscle biopsies suggested blunted anabolic mechanisms in free-living state. Weight and metabolic responses to protein caloric supplementation has not been yet explored in CT. METHODS:A 2 week overfeeding (additional 600 kcal, 30 g protein, 72 g carbohydrate, and 21 g fat) was performed to compare two groups of CTs (12 women and 11 men) to normal-weight controls (12 women and 10 men). Bodyweight, food intake, energy expenditure, body composition, nitrogen balance, appetite hormones profiles, and urine metabolome were monitored before and after overfeeding. RESULTS:Before overfeeding, positive energy gap was found in both CT genders (309 ± 370 kcal in CT-F and 332 ± 709 kcal in CT-M) associated with higher relative protein intake per kilo (1.74 ± 0.32 g/kg/day in CT-F vs. 1.16 ± 0.23 in C-F, P < 0.0001; 1.56 ± 0.36 in CT-M vs. 1.22 ± 0.32 in C-M, P = 0.03), lower nitrogen (7.26 ± 2.36 g/day in CT-F vs. 11.41 ± 3.64 in C-F, P = 0.003; 9.70 ± 3.85 in CT-M vs. 14.14 ± 4.19 in C-M, P = 0.02), but higher essential amino acids urinary excretion (CT/C fold change of 1.13 for leucine and 1.14 for arginine) in free-living conditions. After overfeeding, CTs presented an accentuated positive energy gap, still higher than in controls (675 ± 540 in CTs vs. 379 ± 427 in C, P = 0.04). Increase in lean mass was induced in both controls genders but not in CTs (a trend was noticed in CT women), despite a similar nitrogen balance after overfeeding (5.06 ± 4.33 g/day in CTs vs. 4.28 ± 3.15 in controls, P = 0.49). Higher anorectic gut hormones' tone, glucagon-like peptide 1 and peptide tyrosine tyrosine, during test meal and higher snacking frequency were noticed before and after overfeeding in CTs. CONCLUSIONS:The blunted muscle energy mechanism, previously described in CTs in free-living state, is associated with basal saturated protein turn over suggested by the concordance of positive nitrogen balance and an increased urine excretion of several essential amino acids. This saturation cannot be overpassed by increasing this spontaneous high-protein intake suggesting a resistance to lean mass gain in CT phenotype.

SUBMITTER: Ling Y

PROVIDER: S-EPMC7567161 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Resistance to lean mass gain in constitutional thinness in free-living conditions is not overpassed by overfeeding.

Ling Yiin Y Galusca Bogdan B Martin François-Pierre FP Bartova Simona S Carayol Jérôme J Moco Sofia S Epelbaum Jacques J Grouselle Dominique D Boirie Yves Y Montaurier Christophe C Cuenco Joyceline J Minnion James S JS Thomas Thierry T Mure Sylvie S Hager Jörg J Estour Bruno B Gheldof Nele N Germain Natacha N

Journal of cachexia, sarcopenia and muscle 20200410 5

<h4>Background</h4>Constitutional thinness (CT), a non-malnourished underweight state with no eating disorders, is characterized by weight gain resistance to high fat diet. Data issued from muscle biopsies suggested blunted anabolic mechanisms in free-living state. Weight and metabolic responses to protein caloric supplementation has not been yet explored in CT.<h4>Methods</h4>A 2 week overfeeding (additional 600 kcal, 30 g protein, 72 g carbohydrate, and 21 g fat) was performed to compare two g ...[more]

PMID: 32274897

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Project description:Contrasting with obesity, constitutional thinness (CT) is a rare condition of natural low bodyweight. CT exhibits preserved menstruation in females, no biological marker of undernutrition, no eating disorders but a bodyweight gain desire. Anorexigenic hormonal profile with high peptide tyrosine tyrosine (PYY) was shown in circadian profile. CT could be considered as the opposite of obesity, where some patients appear to resist diet-induced bodyweight loss.The objective of this study was to evaluate appetite regulatory hormones in CTs in an inverse paradigm of diet-induced weight loss.A 4-week fat overfeeding (2640?kJ excess) was performed to compare eight CT women (body mass index (BMI)<17.5?kg?m(-)(2)) to eight female controls (BMI 18.5-25?kg?m(-)(2)). Appetite regulatory hormones profile after test meal, food intake, bodyweight, body composition, energy expenditure and urine metabolomics profiles were monitored before and after overfeeding.After overfeeding, fasting total and acylated ghrelin were significantly lower in CTs than in controls (P=0.01 and 0.03, respectively). After overfeeding, peptide tyrosine tyrosine (PYY) and glucagon-like-peptide 1 both presented earlier (T15 min vs T30 min) and higher post-meal responses (incremental area under the curve) in CTs compared with controls. CTs failed to increase bodyweight (+0.22±0.18?kg, P=0.26 vs baseline), contrasting with controls (+0.72±0.26?kg, P=0.03 vs baseline, P=0.01 vs CTs). Resting energy expenditure increased in CTs only (P=0.031 vs baseline). After overfeeding, a significant negative difference between total energy expenditure and food intake was noticed in CTs only (-2754±720?kJ, P=0.01).CTs showed specific adaptation to fat overfeeding: overall increase in anorexigenic hormonal profile, enhanced post prandial GLP-1 and PYY and inverse to controls changes in urine metabolomics. Overfeeding revealed a paradoxical positive energy balance contemporary to a lack of bodyweight gain, suggesting yet unknown specific energy expenditure pathways in CTs.

Project description:BackgroundGreater increase in 24-h energy expenditure (24EE) during overfeeding and smaller decrease in 24EE during fasting ("spendthrift" metabolic phenotype) are associated with more weight loss during sustained caloric restriction in overweight subjects.ObjectivesThe aim of this study was to investigate whether these acute metabolic responses can also predict weight gain during sustained overfeeding in lean individuals.MethodsSeven lean men participated in this study. Prior to overfeeding, 24EE responses to fasting and 200% normal-protein overfeeding were measured in a whole-room indirect calorimeter. Volunteers underwent 6 wk of 150% low-protein (2%) overfeeding followed by another wk of weight-maintaining diet, during which 24EE was revaluated. Body composition, 24EE, and various hormone concentrations, including fibroblast growth factor 21 (FGF21), were assessed at baseline, at wk 1, 3, and 6 of the overfeeding period, and 1 wk following overfeeding through the use of dual-energy X-ray absorptiometry, indirect calorimetry, and ELISA. Cumulative energy surplus was calculated from 24EE, daily physical activity, and direct measurements of calories of nutrient intake, feces, and urine by bomb calorimetry.ResultsThe average weight gain during 6 wk of low-protein overfeeding was 3.8 kg (6.1%, min: +2.5%, max: +8.0%). During 24-h fasting at baseline, 24EE decreased on average (mean ± SD) by 158 ± 81 kcal/d (P = 0.007). Subjects with less 24EE decrease during fasting (more metabolically spendthrift individuals) gained less weight (r = -0.84, P = 0.03), less fat mass (r = -0.81, P = 0.049), and stored less calories (r = -0.91, P = 0.03) during overfeeding. Following overfeeding, increased 24EE above requirements for achieved body size was associated with less weight and fat mass gain (r = -0.78, P = 0.04) and with the increase in 24EE during 200% normal-protein overfeeding measured at baseline (r = 0.91, P = 0.005). Serum FGF21 concentrations increased up to 44-fold during overfeeding (P < 0.0001).ConclusionsLow-protein overfeeding may be an important tool to identify metabolic phenotypes (spendthrift compared with thrifty) that characterize susceptibility to weight gain. This trial was registered at clinicaltrials.gov as NCT00687115.

Project description:BackgroundLean / Fat Free Body Mass (LBM) is metabolically involved in active processes such as resting energy expenditure, glucose uptake, and myokine secretion. Nonetheless, its association with insulin sensitivity / resistance / glucose tolerance and metabolic syndrome remains unclear in childhood.MethodsThe current investigation aimed to examine the differences in fat-free mass /lean body mass according to the presence of insulin sensitivity/insulin resistance/glucose tolerance/metabolic syndrome in children. A systematic search was carried out in Medline/PubMed, Embase, Scopus, Web of Science, and SciELO, covering the period from each database's respective start to 21 June 2021. Two researchers evaluated 7111 studies according to the inclusion criteria: original human studies, written in English or Spanish, evaluating fat-free mass/lean body mass in children and adolescents including both with and without insulin sensitivity/insulin resistance /glucose tolerance and metabolic syndrome and reported the differences between them in terms of fat free mass/lean body mass. The results of the studies were combined with insulin sensitivity, insulin, resistance, glucose tolerance and metabolic syndrome. The standardized mean difference (SMD) in each study was calculated and combined using the random-effects model. Heterogeneity between studies was tested using the index of heterogeneity (I2), leave-one-out sensitivity analyses were performed, and publication bias was assessed using the Egger and Begg tests.ResultsFinally, 15 studies which compared groups defined according to different glucose homeostasis criteria or metabolic syndrome out of 103 eligible studies were included in this systematic review and 12 studies in the meta-analysis. Meta-analysis showed lower fat-free mass/lean body mass percentage in participants with insulin resistance/glucose tolerance/metabolic syndrome (SMD -0.47; 95% CI, - 0.62 to - 0.32) while in mass units (kg), higher values were found in the same group (SMD, 1.01; 95% CI, 0.43 to 1.60).ConclusionsOur results identified lower values of fat-free mass/lean body mass (%) in children and adolescents with insulin resistance/glucose tolerance/metabolic syndrome and higher values of fat-free mass/lean body mass when these are expressed in kg. The evidence of the impact of lean mass on children's glucose homeostasis or metabolic syndrome is limited, so future studies research should focus on explaining the effect of fat-free mass/lean body mass on different metabolic outcomes. Moreover, it may be interesting to evaluate the quality (muscle density) or functional (muscle strength) outcomes in addition to both absolute (kg) and relative (%) values in future studies. The systematic review was prospectively registered at PROSPERO (registration number CRD42019124734; available at: http://www.crd.york.ac.uk/prospero [accessed: 05 April 2019]).

Dataset Information

Resistance to lean mass gain in constitutional thinness in free-living conditions is not overpassed by overfeeding.

Publications

Resistance to lean mass gain in constitutional thinness in free-living conditions is not overpassed by overfeeding.

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