Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity
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Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity. / Beck Jørgensen, Sebastian; O'Neill, Hayley M; Sylow, Lykke; Honeyman, Jane; Hewitt, Kimberly A; Palanivel, Rengasamy; Fullerton, Morgan D; Öberg, Lisa; Balendran, Anudharan; Galic, Sandra; van der Poel, Chris; Trounce, Ian A; Lynch, Gordon S; Schertzer, Jonathan D; Steinberg, Gregory R.
In: Diabetes, Vol. 62, No. 1, 2013, p. 56-64.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity
AU - Beck Jørgensen, Sebastian
AU - O'Neill, Hayley M
AU - Sylow, Lykke
AU - Honeyman, Jane
AU - Hewitt, Kimberly A
AU - Palanivel, Rengasamy
AU - Fullerton, Morgan D
AU - Öberg, Lisa
AU - Balendran, Anudharan
AU - Galic, Sandra
AU - van der Poel, Chris
AU - Trounce, Ian A
AU - Lynch, Gordon S
AU - Schertzer, Jonathan D
AU - Steinberg, Gregory R
N1 - CURIS 2013 NEXS 284
PY - 2013
Y1 - 2013
N2 - Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver. Skeletal muscle is an important tissue for controlling energy expenditure and whole-body insulin sensitivity; however, the physiological importance of SOCS3 in this tissue has not been examined. Therefore, we generated mice that had SOCS3 specifically deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance.
AB - Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver. Skeletal muscle is an important tissue for controlling energy expenditure and whole-body insulin sensitivity; however, the physiological importance of SOCS3 in this tissue has not been examined. Therefore, we generated mice that had SOCS3 specifically deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance.
KW - Animals
KW - Insulin Receptor Substrate Proteins
KW - Insulin Resistance
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Muscle, Skeletal
KW - Obesity
KW - Phosphorylation
KW - Suppressor of Cytokine Signaling Proteins
KW - Triglycerides
U2 - 10.2337/db12-0443
DO - 10.2337/db12-0443
M3 - Journal article
C2 - 22961088
VL - 62
SP - 56
EP - 64
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 1
ER -
ID: 74335578