Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Academic Article uri icon

Overview

MeSH

  • Animals
  • Disease Susceptibility
  • Hypercholesterolemia
  • Lipoproteins
  • Liver Diseases
  • Mice
  • Mice, Knockout
  • Receptor, Insulin

MeSH Major

  • Atherosclerosis
  • Dyslipidemias
  • Insulin Resistance

abstract

  • Insulin resistance plays a central role in the development of the metabolic syndrome, but how it relates to cardiovascular disease remains controversial. Liver insulin receptor knockout (LIRKO) mice have pure hepatic insulin resistance. On a standard chow diet, LIRKO mice have a proatherogenic lipoprotein profile with reduced high-density lipoprotein (HDL) cholesterol and very low-density lipoprotein (VLDL) particles that are markedly enriched in cholesterol. This is due to increased secretion and decreased clearance of apolipoprotein B-containing lipoproteins, coupled with decreased triglyceride secretion secondary to increased expression of Pgc-1 beta (Ppargc-1b), which promotes VLDL secretion, but decreased expression of Srebp-1c (Srebf1), Srebp-2 (Srebf2), and their targets, the lipogenic enzymes and the LDL receptor. Within 12 weeks on an atherogenic diet, LIRKO mice show marked hypercholesterolemia, and 100% of LIRKO mice, but 0% of controls, develop severe atherosclerosis. Thus, insulin resistance at the level of the liver is sufficient to produce the dyslipidemia and increased risk of atherosclerosis associated with the metabolic syndrome.

publication date

  • February 2008

has subject area

  • Animals
  • Atherosclerosis
  • Disease Susceptibility
  • Dyslipidemias
  • Hypercholesterolemia
  • Insulin Resistance
  • Lipoproteins
  • Liver Diseases
  • Mice
  • Mice, Knockout
  • Receptor, Insulin

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4251554

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2007.11.013

PubMed ID

  • 18249172

Additional Document Info

start page

  • 125

end page

  • 134

volume

  • 7

number

  • 2