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

Stefania Carobbio, Rachel M. Hagen, Christopher J. Lelliott, Marc Slawik, Gema Medina-Gomez, Chong Yew Tan, Audrey Sicard, Helen J. Atherton, Nuria Barbarroja, Mikael Bjursell, Mohammad Bohlooly-Y, Sam Virtue, Antoinette Tuthill, Etienne Lefai, Martine Laville, Tingting Wu, Robert V. Considine, Hubert Vidal, Dominique Langin, Matej OresicFrancisco J. Tinahones, Jose Manuel Fernandez-Real, Julian L. Griffin, Jaswinder K. Sethi, Miguel López, Antonio Vidal-Puig

Research output: Contribution to journalArticle

41 Scopus citations

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 insulinresistant 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 ongoing metabolic stress.

Original languageEnglish (US)
Pages (from-to)3697-3708
Number of pages12
JournalDiabetes
Volume62
Issue number11
DOIs
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Carobbio, S., Hagen, R. M., Lelliott, C. J., Slawik, M., Medina-Gomez, G., Tan, C. Y., Sicard, A., Atherton, H. J., Barbarroja, N., Bjursell, M., Bohlooly-Y, M., Virtue, S., Tuthill, A., Lefai, E., Laville, M., Wu, T., Considine, R. V., Vidal, H., Langin, D., ... Vidal-Puig, A. (2013). Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity. Diabetes, 62(11), 3697-3708. https://doi.org/10.2337/db12-1748