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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

Nutrient intake of HF plus Ensure® diet in Muscle-DN mice. (A) Raw caloric intake by dietary source, 59% HF diet or Ensure®, from data used for computational modeling of intake shown in Figure 2A. (B) Total, carbohydrate, fat or protein caloric intake from combined HF plus Ensure® diets. Note that although total intake is similar, mutant mice consume relatively more calories from Ensure® and less from HF diet than do WT mice. This causes a difference in carbohydrate and fat intake between genotypes. n = 5-6 per group. Statistical significance by repeated measures ANOVA between genotypes for total HF or Ensure® intake (A) as indicated or for macronutrient intake (B) where *P < 0.05 and **P < 0.01.
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Figure 5: Nutrient intake of HF plus Ensure® diet in Muscle-DN mice. (A) Raw caloric intake by dietary source, 59% HF diet or Ensure®, from data used for computational modeling of intake shown in Figure 2A. (B) Total, carbohydrate, fat or protein caloric intake from combined HF plus Ensure® diets. Note that although total intake is similar, mutant mice consume relatively more calories from Ensure® and less from HF diet than do WT mice. This causes a difference in carbohydrate and fat intake between genotypes. n = 5-6 per group. Statistical significance by repeated measures ANOVA between genotypes for total HF or Ensure® intake (A) as indicated or for macronutrient intake (B) where *P < 0.05 and **P < 0.01.

Mentions: We noticed an unexpected difference in food intake between genotypes on the HF plus Ensure® diet which affected the calculated FQ shown in Figure 4B. Both WT and Muscle-DN mice initially consumed more Ensure® compared to the HF diet based on caloric intake from each source (Figure 5A). However, Muscle-DN drank more of the Ensure® diet and ate less of the HF diet than did WT mice. Eventually, WT mice consumed an equal number of calories from Ensure® as from the HF diet, while Muscle-DN mice maintained a large gap between intake of each dietary source. Although the overall caloric intake was similar between genotypes, this disparity resulted in a significantly higher carbohydrate intake and lower fat intake in Muscle-DN mice compared to WT mice due to the differences in macronutrient composition between the HF and the Ensure® diets (Figure 5B and 4A). This disparity also meant that the FQ for WT mice was different than the FQ for Muscle-DN mice for the HF plus Ensure® diet (Figure 4B). Protein intake was similar because the 60% HF and the Ensure® diets have the same amount of metabolizable energy from protein (Figure 5B).


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)

Nutrient intake of HF plus Ensure® diet in Muscle-DN mice. (A) Raw caloric intake by dietary source, 59% HF diet or Ensure®, from data used for computational modeling of intake shown in Figure 2A. (B) Total, carbohydrate, fat or protein caloric intake from combined HF plus Ensure® diets. Note that although total intake is similar, mutant mice consume relatively more calories from Ensure® and less from HF diet than do WT mice. This causes a difference in carbohydrate and fat intake between genotypes. n = 5-6 per group. Statistical significance by repeated measures ANOVA between genotypes for total HF or Ensure® intake (A) as indicated or for macronutrient intake (B) where *P < 0.05 and **P < 0.01.
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Related In: Results  -  Collection

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Figure 5: Nutrient intake of HF plus Ensure® diet in Muscle-DN mice. (A) Raw caloric intake by dietary source, 59% HF diet or Ensure®, from data used for computational modeling of intake shown in Figure 2A. (B) Total, carbohydrate, fat or protein caloric intake from combined HF plus Ensure® diets. Note that although total intake is similar, mutant mice consume relatively more calories from Ensure® and less from HF diet than do WT mice. This causes a difference in carbohydrate and fat intake between genotypes. n = 5-6 per group. Statistical significance by repeated measures ANOVA between genotypes for total HF or Ensure® intake (A) as indicated or for macronutrient intake (B) where *P < 0.05 and **P < 0.01.
Mentions: We noticed an unexpected difference in food intake between genotypes on the HF plus Ensure® diet which affected the calculated FQ shown in Figure 4B. Both WT and Muscle-DN mice initially consumed more Ensure® compared to the HF diet based on caloric intake from each source (Figure 5A). However, Muscle-DN drank more of the Ensure® diet and ate less of the HF diet than did WT mice. Eventually, WT mice consumed an equal number of calories from Ensure® as from the HF diet, while Muscle-DN mice maintained a large gap between intake of each dietary source. Although the overall caloric intake was similar between genotypes, this disparity resulted in a significantly higher carbohydrate intake and lower fat intake in Muscle-DN mice compared to WT mice due to the differences in macronutrient composition between the HF and the Ensure® diets (Figure 5B and 4A). This disparity also meant that the FQ for WT mice was different than the FQ for Muscle-DN mice for the HF plus Ensure® diet (Figure 4B). Protein intake was similar because the 60% HF and the Ensure® diets have the same amount of metabolizable energy from protein (Figure 5B).

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