TY - JOUR
T1 - Hepatic Stearoyl-CoA Desaturase-1 Deficiency Protects Mice from Carbohydrate-Induced Adiposity and Hepatic Steatosis
AU - Miyazaki, Makoto
AU - Flowers, Matthew T.
AU - Sampath, Harini
AU - Chu, Kiki
AU - Otzelberger, Carolin
AU - Liu, Xueqing
AU - Ntambi, James M.
N1 - Funding Information:
We thank members of the transgenic animal facility at Biotechnology Center, University of Wisconsin-Madison. This work was supported by NIH grant RO1DK-62388 (to J.M.N). M.T.F. was supported by an NIH postdoctoral training grant (DK007665). We thank Dr. Jay Horton for providing the SREBP antibodies.
PY - 2007/12/5
Y1 - 2007/12/5
N2 - Stearoyl-CoA desaturase-1 (SCD1), a critical regulator of energy metabolism, catalyzes the synthesis of monounsaturated fats. To understand the tissue-specific role of SCD1 in energy homeostasis, we used Cre-lox technology to generate mice with a liver-specific knockout of Scd1 (LKO). LKO mice were protected from high-carbohydrate, but not high-fat (HF), diet-induced adiposity and hepatic steatosis. Additionally, on a high-sucrose, very low-fat (HSVLF) diet, lipogenesis and levels of nuclear SREBP-1 and ChREBP were significantly decreased in the livers of LKO relative to Scd1lox/lox (Lox) mice. HSVLF feeding in LKO mice caused hypoglycemia and hepatic carbohydrate reduction due to an impairment of gluconeogenesis. Oleate, but not stearate, supplementation normalized adiposity, gluconeogenesis, triglyceride secretion, and hepatic lipogenesis of LKO mice. These results indicate that hepatic SCD1 expression (and thus, oleate) is required for carbohydrate-induced adiposity, but SCD1 inhibition in extrahepatic tissues is required to protect mice from HF-induced obesity and insulin resistance.
AB - Stearoyl-CoA desaturase-1 (SCD1), a critical regulator of energy metabolism, catalyzes the synthesis of monounsaturated fats. To understand the tissue-specific role of SCD1 in energy homeostasis, we used Cre-lox technology to generate mice with a liver-specific knockout of Scd1 (LKO). LKO mice were protected from high-carbohydrate, but not high-fat (HF), diet-induced adiposity and hepatic steatosis. Additionally, on a high-sucrose, very low-fat (HSVLF) diet, lipogenesis and levels of nuclear SREBP-1 and ChREBP were significantly decreased in the livers of LKO relative to Scd1lox/lox (Lox) mice. HSVLF feeding in LKO mice caused hypoglycemia and hepatic carbohydrate reduction due to an impairment of gluconeogenesis. Oleate, but not stearate, supplementation normalized adiposity, gluconeogenesis, triglyceride secretion, and hepatic lipogenesis of LKO mice. These results indicate that hepatic SCD1 expression (and thus, oleate) is required for carbohydrate-induced adiposity, but SCD1 inhibition in extrahepatic tissues is required to protect mice from HF-induced obesity and insulin resistance.
KW - HUMDISEASE
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U2 - 10.1016/j.cmet.2007.10.014
DO - 10.1016/j.cmet.2007.10.014
M3 - Article
C2 - 18054317
AN - SCOPUS:36448991861
SN - 1550-4131
VL - 6
SP - 484
EP - 496
JO - Cell Metabolism
JF - Cell Metabolism
IS - 6
ER -