Remodeling the integration of lipid metabolism between liver and adipose tissue by dietary methionine restriction in rats

Barbara E. Hasek, Anik Boudreau, Jeho Shin, Daorong Feng, Matthew Hulver, Nancy T. Van, Amanda Laque, Laura K. Stewart, Kirsten P. Stone, Desiree Wanders, Sujoy Ghosh, Jeffrey E. Pessin, Thomas W. Gettys

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Dietary methionine restriction (MR) produces an integrated series of biochemical and physiological responses that improve biomarkers of metabolic health, limit fat accretion, and enhance insulin sensitivity. Using transcriptional profiling to guide tissuespecific evaluations of molecular responses to MR, we report that liver and adipose tissue are the primary targets of a transcriptional program that remodeled lipid metabolism in each tissue. The MR diet produced a coordinated downregulation of lipogenic genes in the liver, resulting in a corresponding reduction in the capacity of the liver to synthesize and export lipid. In contrast, the transcriptional response in white adipose tissue (WAT) involved a depot-specific induction of lipogenic and oxidative genes and a commensurate increase in capacity to synthesize and oxidize fatty acids. These responses were accompanied by a significant change in adipocyte morphology, with the MR diet reducing cell size and increasing mitochondrial density across all depots. The coordinated transcriptional remodeling of lipid metabolism between liver and WAT by dietary MR produced an overall reduction in circulating and tissue lipids and provides a potential mechanism for the increase in metabolic flexibility and enhanced insulin sensitivity produced by the diet.

Original languageEnglish (US)
Pages (from-to)3362-3372
Number of pages11
JournalDiabetes
Volume62
Issue number10
DOIs
StatePublished - Oct 1 2013

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Hasek, B. E., Boudreau, A., Shin, J., Feng, D., Hulver, M., Van, N. T., Laque, A., Stewart, L. K., Stone, K. P., Wanders, D., Ghosh, S., Pessin, J. E., & Gettys, T. W. (2013). Remodeling the integration of lipid metabolism between liver and adipose tissue by dietary methionine restriction in rats. Diabetes, 62(10), 3362-3372. https://doi.org/10.2337/db13-0501