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Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Carobbio, Stefania 
Hagen, Rachel M 
Lelliott, Christopher J 
Slawik, Marc 
Medina-Gomez, Gema 

Abstract

The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.

Description

Keywords

3T3-L1 Cells, Adaptation, Physiological, Adipose Tissue, White, Animals, Down-Regulation, Humans, Insulin Resistance, Lipid Metabolism, Membrane Proteins, Mice, Mice, Knockout, Obesity, Obesity, Morbid, RNA, Messenger, Stearoyl-CoA Desaturase, Sterol Regulatory Element Binding Protein 1

Journal Title

Diabetes

Conference Name

Journal ISSN

0012-1797
1939-327X

Volume Title

62

Publisher

American Diabetes Association
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/H002731/1)
Biotechnology and Biological Sciences Research Council (BB/H013539/1)
Biotechnology and Biological Sciences Research Council (BB/H013539/2)
Medical Research Council (G0802051)
Medical Research Council (MC_G0802535)
British Heart Foundation (None)
Medical Research Council (MC_UU_12012/2)
BBSRC (JF16994)
Medical Research Council (G0600717)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_UU_12012/5/B)
Medical Research Council (MC_PC_12012)
Medical Research Council (G0600717/1)