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Modeling Energy Dynamics in Mice with Skeletal Muscle Hypertrophy Fed High Calorie Diets.

Bond ND, Guo J, Hall KD, McPherron AC - Int. J. Biol. Sci. (2016)

Bottom Line: Retrospective and prospective studies show that lean mass or strength is positively associated with metabolic health.Their leanness is often attributed to higher energy expenditure in the face of normal food intake.We have previously developed a computational model to estimate energy output, fat oxidation and respiratory quotient from food intake and body composition measurements to more accurately account for changes in body composition in rodents over time.

View Article: PubMed Central - PubMed

Affiliation: 1. Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 USA;

ABSTRACT
Retrospective and prospective studies show that lean mass or strength is positively associated with metabolic health. Mice deficient in myostatin, a growth factor that negatively regulates skeletal muscle mass, have increased muscle and body weights and are resistant to diet-induced obesity. Their leanness is often attributed to higher energy expenditure in the face of normal food intake. However, even obese animals have an increase in energy expenditure compared to normal weight animals suggesting this is an incomplete explanation. We have previously developed a computational model to estimate energy output, fat oxidation and respiratory quotient from food intake and body composition measurements to more accurately account for changes in body composition in rodents over time. Here we use this approach to understand the dynamic changes in energy output, intake, fat oxidation and respiratory quotient in muscular mice carrying a dominant negative activin receptor IIB expressed specifically in muscle. We found that muscular mice had higher food intake and higher energy output when fed either chow or a high-fat diet for 15 weeks compared to WT mice. Transgenic mice also matched their rate of fat oxidation to the rate of fat consumed better than WT mice. Surprisingly, when given a choice between high-fat diet and Ensure® drink, transgenic mice consumed relatively more calories from Ensure® than from the high-fat diet despite similar caloric intake to WT mice. When switching back and forth between diets, transgenic mice adjusted their intake more rapidly than WT to restore normal caloric intake. Our results show that mice with myostatin inhibition in muscle are better at adjusting energy intake and output on diets of different macronutrient composition than WT mice to maintain energy balance and resist weight gain.

No MeSH data available.


Related in: MedlinePlus

MSTN KO energy intake and computational analysis. (A) Daily caloric intake in KO or WT mice before, during and after switching to 59% HF diet for 14 days (days 22-35). (B) Body weight, lean and fat mass during diet changes. (C) Calculated energy intake, output and balance, and fat intake, oxidation and RQ in WT and MSTN KO mice during diet changes. n = 8-9 per group. Statistical significance between genotypes by student's t test of the daily average intake during an indicated diet interval (A) or by repeated measures ANOVA for body composition measured over time (B); *P < 0.05, **P < 0.01 and **P < 0.001.
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Figure 7: MSTN KO energy intake and computational analysis. (A) Daily caloric intake in KO or WT mice before, during and after switching to 59% HF diet for 14 days (days 22-35). (B) Body weight, lean and fat mass during diet changes. (C) Calculated energy intake, output and balance, and fat intake, oxidation and RQ in WT and MSTN KO mice during diet changes. n = 8-9 per group. Statistical significance between genotypes by student's t test of the daily average intake during an indicated diet interval (A) or by repeated measures ANOVA for body composition measured over time (B); *P < 0.05, **P < 0.01 and **P < 0.001.

Mentions: To determine whether the differences in energy balance and diet preference were generalizable to other mice with MSTN inhibition, we also tested MSTN KO mice. Female MSTN KO mice and WT littermates were fed chow for 3 weeks, switched to a 60% HF diet for 2 weeks and then back to chow (Figure 1B). The cumulative chow intake of female MSTN KO mice over the first 3 weeks of the diet switch experiment (Figure 7A) was 6.5% more than WT littermates which was not significant, although the average daily intake was barely significant [12.6 ± 0.4 vs. 13.7 ± 0.3 kcal/d, WT and MSTN KO, respectively, P = 0.049]. Food intake increased with HF diet feeding for each genotype although not until the second day, but the average daily HF intake was not significantly different between genotypes (Figure 7A; 15.6 ± 0.6 vs. 14.6 ± 0.5 kcal/d, WT and MSTN KO, respectively, P = 0.2). Like Muscle-DN mice, MSTN KO mice more rapidly restored food intake to normal levels after a sharp decline upon being returned to chow feeding (Figure 7A).


Modeling Energy Dynamics in Mice with Skeletal Muscle Hypertrophy Fed High Calorie Diets.

Bond ND, Guo J, Hall KD, McPherron AC - Int. J. Biol. Sci. (2016)

MSTN KO energy intake and computational analysis. (A) Daily caloric intake in KO or WT mice before, during and after switching to 59% HF diet for 14 days (days 22-35). (B) Body weight, lean and fat mass during diet changes. (C) Calculated energy intake, output and balance, and fat intake, oxidation and RQ in WT and MSTN KO mice during diet changes. n = 8-9 per group. Statistical significance between genotypes by student's t test of the daily average intake during an indicated diet interval (A) or by repeated measures ANOVA for body composition measured over time (B); *P < 0.05, **P < 0.01 and **P < 0.001.
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Related In: Results  -  Collection

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Figure 7: MSTN KO energy intake and computational analysis. (A) Daily caloric intake in KO or WT mice before, during and after switching to 59% HF diet for 14 days (days 22-35). (B) Body weight, lean and fat mass during diet changes. (C) Calculated energy intake, output and balance, and fat intake, oxidation and RQ in WT and MSTN KO mice during diet changes. n = 8-9 per group. Statistical significance between genotypes by student's t test of the daily average intake during an indicated diet interval (A) or by repeated measures ANOVA for body composition measured over time (B); *P < 0.05, **P < 0.01 and **P < 0.001.
Mentions: To determine whether the differences in energy balance and diet preference were generalizable to other mice with MSTN inhibition, we also tested MSTN KO mice. Female MSTN KO mice and WT littermates were fed chow for 3 weeks, switched to a 60% HF diet for 2 weeks and then back to chow (Figure 1B). The cumulative chow intake of female MSTN KO mice over the first 3 weeks of the diet switch experiment (Figure 7A) was 6.5% more than WT littermates which was not significant, although the average daily intake was barely significant [12.6 ± 0.4 vs. 13.7 ± 0.3 kcal/d, WT and MSTN KO, respectively, P = 0.049]. Food intake increased with HF diet feeding for each genotype although not until the second day, but the average daily HF intake was not significantly different between genotypes (Figure 7A; 15.6 ± 0.6 vs. 14.6 ± 0.5 kcal/d, WT and MSTN KO, respectively, P = 0.2). Like Muscle-DN mice, MSTN KO mice more rapidly restored food intake to normal levels after a sharp decline upon being returned to chow feeding (Figure 7A).

Bottom Line: Retrospective and prospective studies show that lean mass or strength is positively associated with metabolic health.Their leanness is often attributed to higher energy expenditure in the face of normal food intake.We have previously developed a computational model to estimate energy output, fat oxidation and respiratory quotient from food intake and body composition measurements to more accurately account for changes in body composition in rodents over time.

View Article: PubMed Central - PubMed

Affiliation: 1. Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 USA;

ABSTRACT
Retrospective and prospective studies show that lean mass or strength is positively associated with metabolic health. Mice deficient in myostatin, a growth factor that negatively regulates skeletal muscle mass, have increased muscle and body weights and are resistant to diet-induced obesity. Their leanness is often attributed to higher energy expenditure in the face of normal food intake. However, even obese animals have an increase in energy expenditure compared to normal weight animals suggesting this is an incomplete explanation. We have previously developed a computational model to estimate energy output, fat oxidation and respiratory quotient from food intake and body composition measurements to more accurately account for changes in body composition in rodents over time. Here we use this approach to understand the dynamic changes in energy output, intake, fat oxidation and respiratory quotient in muscular mice carrying a dominant negative activin receptor IIB expressed specifically in muscle. We found that muscular mice had higher food intake and higher energy output when fed either chow or a high-fat diet for 15 weeks compared to WT mice. Transgenic mice also matched their rate of fat oxidation to the rate of fat consumed better than WT mice. Surprisingly, when given a choice between high-fat diet and Ensure® drink, transgenic mice consumed relatively more calories from Ensure® than from the high-fat diet despite similar caloric intake to WT mice. When switching back and forth between diets, transgenic mice adjusted their intake more rapidly than WT to restore normal caloric intake. Our results show that mice with myostatin inhibition in muscle are better at adjusting energy intake and output on diets of different macronutrient composition than WT mice to maintain energy balance and resist weight gain.

No MeSH data available.


Related in: MedlinePlus