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LPS and proinflammatory cytokines decrease lipin-1 in mouse adipose tissue and 3T3-L1 adipocytes.

Biao Lu1, Yang Lu, Arthur H Moser

  • 1Department of Veterans Affairs Medical Center, University of California, San Francisco, CA, USA.

American Journal of Physiology. Endocrinology and Metabolism
|October 23, 2008
PubMed
Summary
This summary is machine-generated.

Infection and inflammation reduce lipin-1, a key triglyceride synthesis enzyme, in adipose tissue. This suppression may increase circulating free fatty acids (FFA) during the acute-phase response.

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Area of Science:

  • Metabolic regulation
  • Molecular biology
  • Immunology

Background:

  • Infection and inflammation trigger the acute-phase response, altering adipose triglyceride metabolism and increasing plasma free fatty acids (FFA) and VLDL.
  • Lipin-1 is a crucial protein regulating adipose differentiation, mitochondrial oxidation, and triglyceride synthesis.

Purpose of the Study:

  • To investigate the regulation of lipin-1 expression in adipose tissue by lipopolysaccharide (LPS), zymosan, and proinflammatory cytokines.
  • To elucidate the molecular pathways involved in LPS-induced lipin-1 repression.

Main Methods:

  • Administration of LPS and zymosan to mice to assess lipin-1 mRNA and protein levels in adipose tissue.
  • Treatment of cultured 3T3-L1 adipocytes with proinflammatory cytokines (TNF-alpha, IL-1beta, IFN-gamma, LPS, IL-6).
  • Analysis of lipin-1 expression in TNF-alpha/IL-1 receptor-null mice following LPS administration.

Main Results:

  • LPS and zymosan administration significantly decreased lipin-1 mRNA and protein levels in mouse adipose tissue, while lipin-2 and -3 mRNA remained unchanged.
  • Proinflammatory cytokines TNF-alpha, IL-1beta, and IFN-gamma, but not LPS or IL-6, reduced lipin-1 mRNA in cultured adipocytes.
  • LPS-induced lipin-1 repression was partially attenuated in TNF-alpha/IL-1 receptor-null mice, indicating roles for these cytokines and others.

Conclusions:

  • Lipin-1 expression is suppressed by LPS, zymosan, and key proinflammatory cytokines in adipose tissue.
  • This suppression may impair triglyceride synthesis in adipocytes, leading to increased FFA release into circulation.
  • Lipin-1 repression contributes to altered lipid metabolism during infection and inflammation.