PMID:11877467

Citation	McPherron, AC and Lee, SJ (2002) Suppression of body fat accumulation in myostatin-deficient mice. J. Clin. Invest. 109:595-601
Abstract	Myostatin is a TGF-beta 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 (A(y)) and obese (Lep(ob/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.
Links	PubMed PMC150888 Online version:10.1172/JCI13562
Keywords	Adipose Tissue/pathology; Animals; Diabetes Mellitus, Type 2/prevention & control; Eating; Female; Glucose/metabolism; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Myostatin; Obesity/prevention & control; Organ Size; Transforming Growth Factor beta/deficiency; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:GDF8	involved_in	GO:0048632: negative regulation of skeletal muscle tissue growth	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:GDF8		GO:0019222: regulation of metabolic process	ECO:0000315:		P		Table 2 shows Mstn–/– mice had higher rates of total and resting O2 consumption compared with Mstn+/+ mice, which is expected given the higher body weights of Mstn–/– mice. If the data are expressed as a function of body weight, however, Mstn–/– mice actually had lower rates of total and resting O2 consumption compared with Mstn+/+ mice.	complete CACAO 3737
MOUSE:GDF8		GO:0048632: negative regulation of skeletal muscle tissue growth	ECO:0000315:		P		Figure 1a shows the increased mass of triceps muscle in Mstn -/- mice at different ages as well as an apparent dose-dependency on muscle mass.	complete CACAO 3750
MOUSE:GDF8		GO:0019216: regulation of lipid metabolic process	ECO:0000315:		P		Figure 1b-g shows the significant differences in fat pad mass between Mstn -/- and Mstn +/+ mice after 2 months of age.	complete CACAO 3753

References

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