RESUMEN
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 Scd1 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 Scd1 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 Igfbp1 is regulated by oleic acid (18:1n9), a product of SCD1, through the mTORC1-FGF21 axis both in vivo and in vitro.
Asunto(s)
Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina , Diana Mecanicista del Complejo 1 de la Rapamicina , Ácido Oléico , Estearoil-CoA Desaturasa , Animales , Ratones , Insulina/metabolismo , Hígado/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Obesidad/metabolismo , Ácido Oléico/metabolismo , Estearoil-CoA Desaturasa/genética , Estearoil-CoA Desaturasa/metabolismo , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Carbohidratos de la Dieta/administración & dosificaciónRESUMEN
Stearoyl-CoA Desaturase-2 (SCD2) is a member of the Stearoyl-CoA Desaturase (SCD) family of enzymes that catalyze the rate-limiting step in monounsaturated fatty acid (MUFA) synthesis. The MUFAs palmitoleoyl-CoA (16:1n7) and oleoyl-CoA (18:1n9) are the major products of SCD2. Palmitoleoyl-CoA and oleoyl-CoA have various roles, from being a source of energy to signaling molecules. Under normal feeding conditions, SCD2 is ubiquitously expressed and is the predominant SCD isoform in the brain. However, obesogenic diets highly induce SCD2 in adipose tissue, lung, and kidney. Here we provide a comprehensive review of SCD2 in mouse development, metabolism, and various diseases, such as obesity, chronic kidney disease, Alzheimer's disease, multiple sclerosis, and Parkinson's disease. In addition, we show that bone mineral density is decreased in SCD2KO mice under high-fat feeding conditions and that SCD2 is not required for preadipocyte differentiation or the expression of PPARγ in vivo despite being required in vitro.
Asunto(s)
Adipocitos/enzimología , Diferenciación Celular , Ácidos Grasos Monoinsaturados/metabolismo , Enfermedades Neurodegenerativas/enzimología , Obesidad/enzimología , Insuficiencia Renal Crónica/enzimología , Estearoil-CoA Desaturasa/metabolismo , Acilcoenzima A/biosíntesis , Acilcoenzima A/genética , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Ratones Noqueados , Enfermedades Neurodegenerativas/genética , Obesidad/inducido químicamente , Obesidad/genética , Obesidad/metabolismo , Palmitoil Coenzima A/biosíntesis , Palmitoil Coenzima A/genética , Insuficiencia Renal Crónica/genética , Estearoil-CoA Desaturasa/genéticaRESUMEN
In mouse, there are four stearoyl-CoA desaturase isoforms (SCD1-4) that catalyze the synthesis of monounsaturated fatty acids. Previously, we have shown that mice harboring a whole body deletion of the SCD1 isoform (SCD1KO) are protected from diet and genetically induced adiposity. Here, we report that global deletion of the SCD2 isoform (SCD2KO) provides a similar protective effect against the onset of both high-fat diet (HFD) and high-carbohydrate diet (HCD) induced adiposity. After 10 weeks of HFD feeding or 6 weeks of HCD feeding, SCD2KO mice failed to gain weight and had decreased fat mass. On HFD, SCD2KO mice remained glucose and insulin tolerant. Lastly, the markers for energy expenditure, UCP1 and PGC-1α, were increased in the brown adipose tissue of HFD fed SCD2KO mice.