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Hepatic Oleate Regulates Insulin-like Growth Factor-Binding Protein 1 Partially through the mTORC1-FGF21 Axis during High-Carbohydrate Feeding
oleh: Lucas M. O’Neill, Yar Xin Phang, Zhaojin Liu, Sarah A. Lewis, Ahmed Aljohani, Ayren McGahee, Gina Wade, Mugagga Kalyesubula, Judith Simcox, James M. Ntambi
Format: | Article |
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Diterbitkan: | MDPI AG 2022-11-01 |
Deskripsi
Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-liming step of monounsaturated fatty acid biosynthesis and is a key regulator of systemic glucose metabolism. Mice harboring either a global (GKO) or liver-specific deletion (LKO) of <i>Scd1</i> display enhanced insulin signaling and whole-body glucose uptake. Additionally, GKO and LKO mice are protected from high-carbohydrate diet-induced obesity. Given that high-carbohydrate diets can lead to chronic metabolic diseases such as obesity, diabetes, and hepatic steatosis, it is critical to understand how <i>Scd1</i> deficiency confers metabolically beneficial phenotypes. Here we show that insulin-like growth factor-binding protein 1 (IGFBP1), a hepatokine that has been reported to enhance insulin signaling, is significantly elevated in the liver and plasma of GKO and LKO mice fed a low-fat high-carbohydrate diet. We also observed that the expression of hepatic <i>Igfbp1</i> is regulated by oleic acid (18:1n9), a product of SCD1, through the mTORC1-FGF21 axis both in vivo and in vitro.