Administration of myostatin does not alter fat mass in adult mice.
OBJECTIVE
Myostatin, a member of the TGF-beta superfamily, is produced by skeletal muscle and acts as a negative regulator of muscle mass. It has also been suggested that low-dose administration of myostatin (2 mug/day) in rodents can reduce fat mass without altering muscle mass. In the current study, we attempted to further explore the effects of myostatin on adipocytes and its potential to reduce fat mass, since myostatin administration could potentially be a useful strategy to treat obesity and its complications in humans.


METHODS
Purified myostatin protein was examined for its effects on adipogenesis and lipolysis in differentiated 3T3-L1 adipocytes as well as for effects on fat mass in wild-type, myostatin null and obese mice.


RESULTS
While myostatin was capable of inhibiting adipogenesis in 3T3-L1 cells, it did not alter lipolysis in fully differentiated adipocytes. Importantly, pharmacological administration of myostatin over a range of doses (2-120 mug/day) did not affect fat mass in wild-type or genetically obese (ob/ob, db/db) mice, although muscle mass was significantly reduced at the highest myostatin dose.


CONCLUSIONS
Our results suggest that myostatin does not reduce adipose stores in adult animals. Contrary to prior indications, pharmacological administration of myostatin does not appear to be an effective strategy to treat obesity in vivo.
Stolz
L E
LE
Department of Cardiovascular and Metabolic Diseases, Wyeth Research, Cambridge, MA 02140, USA.
Li
D
D
Qadri
A
A
Jalenak
M
M
Klaman
L D
LD
Tobin
J F
JF
D041721:3T3-L1 Cells / Q000187:drug effects*; D017667:Adipocytes / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D055435:Myostatin; D009765:Obesity / Q000150:complications / Q000517:prevention & control; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D016896:Treatment Outcome
C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta