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Suppression of body fat accumulation in myostatin-deficient mice
Alexandra C. McPherron, Se-Jin Lee
Alexandra C. McPherron, Se-Jin Lee
Published March 1, 2002
Citation Information: J Clin Invest. 2002;109(5):595-601. https://doi.org/10.1172/JCI13562.
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Article Endocrinology

Suppression of body fat accumulation in myostatin-deficient mice

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Abstract

Myostatin is a TGF-β family member that acts as a negative regulator of muscle growth. Mice lacking the myostatin gene (Mstn) have a widespread increase in skeletal muscle mass resulting from a combination of muscle fiber hypertrophy and hyperplasia. Here we show that Mstn-null mice have a significant reduction in fat accumulation with increasing age compared with wild-type littermates, even in the setting of normal food intake (relative to body weight), normal body temperature, and a slightly decreased resting metabolic rate. To investigate whether myostatin might be an effective target for suppressing the development of obesity in settings of abnormal fat accumulation, we analyzed the effect of the Mstn mutation in two genetic models of obesity, agouti lethal yellow (Ay) and obese (Lepob/ob). In each case, loss of Mstn led to a partial suppression of fat accumulation and of abnormal glucose metabolism. Our findings raise the possibility that pharmacological agents that block myostatin function may be useful not only for enhancing muscle growth, but also for slowing or preventing the development of obesity and type 2 diabetes.

Authors

Alexandra C. McPherron, Se-Jin Lee

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Figure 1

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Mstn deletion suppresses fat accumulation. (a) Increased mass of triceps...
Mstn deletion suppresses fat accumulation. (a) Increased mass of triceps muscle in Mstn–/– mice at different ages (n = 4–13). Black, Mstn+/+; blue, Mstn+/–; pink, Mstn–/–. Data are expressed as mean ± SEM. (b–f) Mass of male epididymal (b), retroperitoneal (c), and inguinal (d), and female parametrial (e) and retroperitoneal (f) fat pads at different ages (n = 4–13). Orange bars designate the mean, and symbols designate individual animals colored as in a, with diamonds for males and circles for females. #P = 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, Student’s t test. (g) Serum concentration of leptin to mass of total body fat in individual 8-month-old male mice. (h) Fat cell histology in epididymal fat pads. Scale bar = 50 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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