Role of caspase-1 in regulation of triglyceride metabolism

Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4810-5. doi: 10.1073/pnas.1301996110. Epub 2013 Mar 4.

Abstract

Caspase-1 is a cysteine protease that can be activated by both endogenous and exogenous inflammatory stimuli and has been shown to have important functions in processes as diverse as proteolytic activation of cytokines, cell death, and membrane repair. Caspase-1-dependent production of the inflammatory cytokines IL-1 and IL-18 has also been implicated in the regulation of appetite, body weight, glucose homeostasis, and lipid metabolism. Consistent with the emerging views of caspase-1 in metabolic regulation, we find that caspase-1-deficient mice have dramatically accelerated triglyceride clearance, without alteration in lipid production or absorption, and resultant decrease in steady-state circulating triglyceride and fatty acid levels. Surprisingly, this effect is independent of IL-1-family signaling, supporting the concept that caspase-1 influences lipid metabolism through multiple mechanisms, not limited to cytokines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / metabolism*
  • Fatty Acids / genetics
  • Fatty Acids / metabolism*
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Lipid Metabolism / physiology*
  • Mice
  • Mice, Knockout
  • Triglycerides / genetics
  • Triglycerides / metabolism*

Substances

  • Fatty Acids
  • Interleukin-1
  • Triglycerides
  • Caspase 1