Remodeling the Integration of Lipid Metabolism Between Liver and Adipose Tissue by Dietary Methionine Restriction in Rats

  1. Thomas W. Gettys1
  1. 1Laboratories of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana
  2. 2Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York
  3. 3Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, Virginia
  4. 4Laboratory of Computational Biology, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
  1. Corresponding author: Thomas W. Gettys, gettystw{at}pbrc.edu.
  1. S.G. is currently affiliated with the Cardiovascular and Metabolic Disease Program and Center for Computational Biology, Duke-NUS Graduate Medical School, Singapore.

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 tissue-specific 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.

Footnotes

  • Received March 27, 2013.
  • Accepted June 19, 2013.

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  1. Diabetes vol. 62 no. 10 3362-3372
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