Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity

Matthew T Flowers,Lacmbouh Ade,James M Ntambi,Maggie S Strable

doi:10.1194/jlr.m027508

Matthew T Flowers, Lacmbouh Ade + Show 2 more

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https://doi.org/10.1194/jlr.m027508

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Abstract

Stearoyl-CoA desaturase 1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated FA. Mice with whole-body or skin-specific deletion of SCD1 are resistant to obesity. Here, we show that mice lacking SCD1 in adipose and/or liver are not protected from either genetic- (agouti; A(y)/a) or diet-induced obesity (DIO) despite a robust reduction in SCD1 MUFA products in both subcutaneous and epididymal white adipose tissue. Adipose SCD1 deletion had no effect on glucose or insulin tolerance or on hepatic triglyceride (TG) accumulation. Interestingly, lack of SCD1 from liver lowered the MUFA levels of adipose tissue and vice versa, as reflected by the changes in FA composition. Simultaneous deletion of SCD1 from liver and adipose resulted in a synergistic lowering of tissue MUFA levels, especially in the A(y)/a model in which glucose tolerance was also improved. Lastly, we found that liver and plasma TG show nearly identical genotype-dependent differences in FA composition, indicating that FA composition of plasma TG is predictive for hepatic SCD1 activity and TG FA composition. The current study suggests that SCD1 deletion from adipose and/or liver is insufficient to elicit protection from obesity, but it supports the existence of extensive lipid cross-talk between liver and adipose tissue.

Highlights

Stearoyl-CoA desaturase 1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated FA
We recently reported that mice with a skin-specific deletion of Scd1 (SKO mice) recapitulated the hypermetabolic phenotype observed in global SCD1 knockout (GKO) mice, indicating that the skin is a major contributor to the altered energy metabolism observed in GKO mice [5]
Immunoblot analysis confirmed the deletion of Scd1 from white and brown adipose tissue of adipose SCD1 knockout (AKO) and liver/adipose SCD1 knockout (LAKO) mice, and from liver of liver SCD1 knockout (LKO) and LAKO mice (Fig. 1A)

Summary

Introduction

Stearoyl-CoA desaturase 1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated FA. Adipose SCD1 deletion had no effect on glucose or insulin tolerance or on hepatic triglyceride (TG) accumulation. Lack of SCD1 from liver lowered the MUFA levels of adipose tissue and vice versa, as reflected by the changes in FA composition. Simultaneous deletion of SCD1 from liver and adipose resulted in a synergistic lowering of tissue MUFA levels, especially in the Ay/a model in which glucose tolerance was improved. The current study suggests that SCD1 deletion from adipose and/or liver is insufficient to elicit protection from obesity, but it supports the existence of extensive lipid cross-talk between liver and adipose tissue.— Flowers, M. Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity.

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