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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

Body composition of Muscle-DN mice fed chow, HF (59% fat) diet or HF (59% fat) diet plus Ensure®. (A) Body weight (BW), (B) lean mass and (C) fat mass were measured weekly for 15 weeks beginning at ~9 weeks of age. Chow, n = 6-7; HF, n = 5-8 per group; HF + Ensure®, n = 5-6 per group. *P < 0.01; **P < 0.001 between genotypes on the same diet by repeated measures ANOVA.
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Figure 2: Body composition of Muscle-DN mice fed chow, HF (59% fat) diet or HF (59% fat) diet plus Ensure®. (A) Body weight (BW), (B) lean mass and (C) fat mass were measured weekly for 15 weeks beginning at ~9 weeks of age. Chow, n = 6-7; HF, n = 5-8 per group; HF + Ensure®, n = 5-6 per group. *P < 0.01; **P < 0.001 between genotypes on the same diet by repeated measures ANOVA.

Mentions: Mice expressing a dominant negative activin receptor type IIB specifically in skeletal muscle (Muscle-DN mice) were previously shown to have increased muscle mass, reduced fat mass, resistance to diet-induced obesity and improved insulin sensitivity compared to WT littermates 10,32,34. To measure changes in energy intake and body composition over time in WT and Muscle-DN mice, animals were individually housed and fed either chow, HF diet with 59% of calories from fat or the same HF diet plus Ensure® starting at ~9 weeks of age (Figure 1A). Body weight, lean mass and fat mass are shown in Figure 2. On standard chow diet, Muscle-DN mice weighed more than WT mice throughout the time course (Figure 2A). This difference was largely due to higher lean mass with Muscle-DN mice having ~8.3 g more lean mass compared to WT mice (Figure 2B). Both WT and Muscle-DN mice had low fat mass at the youngest age studied, although even then Muscle-DN mice already had significantly less fat mass (Figure 2C; WT, 1.86 g ± 0.42; Muscle-DN, 1.15 g ± 0.36, P < 0.01). However, WT mice gained ~6.4 g of fat during the course of the experiment while Muscle-DN mice gained only ~0.8 g of fat giving Muscle-DN mice ~75% less total fat mass by the end of the 15-week time period.


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)

Body composition of Muscle-DN mice fed chow, HF (59% fat) diet or HF (59% fat) diet plus Ensure®. (A) Body weight (BW), (B) lean mass and (C) fat mass were measured weekly for 15 weeks beginning at ~9 weeks of age. Chow, n = 6-7; HF, n = 5-8 per group; HF + Ensure®, n = 5-6 per group. *P < 0.01; **P < 0.001 between genotypes on the same diet by repeated measures ANOVA.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4829546&req=5

Figure 2: Body composition of Muscle-DN mice fed chow, HF (59% fat) diet or HF (59% fat) diet plus Ensure®. (A) Body weight (BW), (B) lean mass and (C) fat mass were measured weekly for 15 weeks beginning at ~9 weeks of age. Chow, n = 6-7; HF, n = 5-8 per group; HF + Ensure®, n = 5-6 per group. *P < 0.01; **P < 0.001 between genotypes on the same diet by repeated measures ANOVA.
Mentions: Mice expressing a dominant negative activin receptor type IIB specifically in skeletal muscle (Muscle-DN mice) were previously shown to have increased muscle mass, reduced fat mass, resistance to diet-induced obesity and improved insulin sensitivity compared to WT littermates 10,32,34. To measure changes in energy intake and body composition over time in WT and Muscle-DN mice, animals were individually housed and fed either chow, HF diet with 59% of calories from fat or the same HF diet plus Ensure® starting at ~9 weeks of age (Figure 1A). Body weight, lean mass and fat mass are shown in Figure 2. On standard chow diet, Muscle-DN mice weighed more than WT mice throughout the time course (Figure 2A). This difference was largely due to higher lean mass with Muscle-DN mice having ~8.3 g more lean mass compared to WT mice (Figure 2B). Both WT and Muscle-DN mice had low fat mass at the youngest age studied, although even then Muscle-DN mice already had significantly less fat mass (Figure 2C; WT, 1.86 g ± 0.42; Muscle-DN, 1.15 g ± 0.36, P < 0.01). However, WT mice gained ~6.4 g of fat during the course of the experiment while Muscle-DN mice gained only ~0.8 g of fat giving Muscle-DN mice ~75% less total fat mass by the end of the 15-week time period.

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