Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity.
Author(s)
Type
Journal Article
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.
Date Issued
2013-11
Date Acceptance
2013-08-01
Citation
Diabetes, 2013, 62 (11), pp.3697-3708
ISSN
0012-1797
Publisher
American Diabetes Association
Start Page
3697
End Page
3708
Journal / Book Title
Diabetes
Volume
62
Issue
11
Copyright Statement
© 2013 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/23919961
PII: db12-1748
Subjects
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
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2013-08-06