Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion

J Lipid Res. 2013 Feb;54(2):448-56. doi: 10.1194/jlr.M031963. Epub 2012 Nov 17.

Abstract

Caspase-1 is known to activate the proinflammatory cytokines IL-1β and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1 deficiency reduced the postprandial TG response to an oral lipid load, whereas TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [(3)H]TG-labeled very low-density lipoprotein (VLDL)-like emulsion particles. An oral gavage of [(3)H]TG-containing olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1 deficiency did not affect FA oxidation or FA uptake but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins. The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Animals
  • Caspase 1 / deficiency*
  • Feces / chemistry
  • Gene Expression Regulation / drug effects
  • Intestinal Absorption* / drug effects
  • Lipogenesis / drug effects
  • Lipogenesis / genetics
  • Lipoproteins, VLDL / biosynthesis
  • Liver / drug effects
  • Liver / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Olive Oil
  • Plant Oils / pharmacology
  • Postprandial Period / drug effects
  • Triglycerides / biosynthesis
  • Triglycerides / metabolism*

Substances

  • Lipoproteins, VLDL
  • Olive Oil
  • Plant Oils
  • Triglycerides
  • Caspase 1