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J Biol Chem. 2019 Nov 5. pii: jbc.RA119.009868. doi: 10.1074/jbc.RA119.009868. [Epub ahead of print]

Hepatic stearoyl CoA desaturase 1 deficiency increases glucose uptake in adipose tissue partially through the PGC-1α-FGF21 axis in mice.

Author information

1
King Saud bin Abdulaziz University, Saudi Arabia.
2
King Abdulaziz University, Saudi Arabia.
3
University of Wisconsin-Madison, United States.
4
University of Wisconsin-Madison.
5
University of Wisconsin, United States.
6
Biochemistry, University of Wisconsin-Madison, United States.

Abstract

Increased carbohydrate consumption increases hepatic de novo lipogenesis, which has been linked to the development of chronic metabolic diseases, including obesity, hepatic steatosis, and insulin resistance. Stearoyl CoA desaturase 1 (SCD1) is a critical lipogenic enzyme that catalyzes the synthesis of two monounsaturated fatty acids (MUFA), oleate and palmitoleate, from the saturated fatty acids, stearate and palmitate, respectively. SCD1-deficient mouse models are protected against diet-induced adiposity, hepatic steatosis, and hyperglycemia. However, the mechanism of this protection by SCD1 deficiency is unclear. Using a liver-specific SCD1 knockout (LKO) mouse model fed a high-carbohydrate, low-fat diet (HCD), we show that hepatic SCD1 deficiency increases systemic glucose uptake. Hepatic SCD1 deficiency enhanced glucose transporter type 1 (GLUT1) expression in the liver and also up-regulated GLUT4 and adiponectin expression in the adipose tissue. The enhanced glucose uptake correlated with increased liver expression and elevated plasma levels of fibroblast growth factor 21 (FGF21), a hepatokine known to increase systemic insulin sensitivity and to regulate whole-body lipid metabolism. Feeding LKO mice with triolein-supplemented, but not tristearin-supplemented, HCD reduced FGF21 expression and plasma levels. Consistently, SCD1 inhibition in primary hepatocytes induced FGF21 expression, which was repressed by treatment with oleate but not palmitoleate. Moreover, deletion of the transcriptional coactivator PPARg coactivator 1α (PGC-1α) reduced hepatic and plasma FGF21 and white adipocyte tissue-specific GLUT4 expression and raised plasma glucose levels in the LKO mice. These results suggest that hepatic oleate regulates glucose uptake in adipose tissue either directly or partially by modulating the hepatic PGC-1α-FGF21 axis.

KEYWORDS:

Glucose transporters-Insulin sensitivity; Heptokine-FGF21; Liver-adipocyte-crosstalk; Monounsaturated fatty acids; Stearoyl-CoA Desaturase-1; adiponectin; carbohydrate metabolism; fibroblast growth factor (FGF); glucose metabolism; glucose transport; lipid metabolism; lipid signaling; liver; liver metabolism; obesity

PMID:
31690632
DOI:
10.1074/jbc.RA119.009868
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