Adipocyte-specific disruption of mouse Cnot3 causes lipodystrophy

FEBS Lett. 2017 Jan;591(2):358-368. doi: 10.1002/1873-3468.12550. Epub 2017 Jan 12.

Abstract

Lipodystrophy involves a loss of adipose tissue. In mice, disruption of adipose tissue Cnot3, a subunit of the CCR4-NOT deadenylase complex, causes adipose tissue anomalies. In Cnot3ad-/- mice, white adipose tissue (WAT) decreases concomitantly with enhanced inflammation, whereas brown adipose tissue increases and contains larger lipid droplets. Cnot3ad-/- mice show hyperinsulinemia, hyperglycemia, insulin resistance, and glucose intolerance, and cannot maintain body temperature during cold exposure. Increased expression of inflammatory genes and decreased leptin expression also occur in Cnot3ad-/- WAT, achieving levels similar to those in lipodystrophic aP2-nSrebp1c and Ppargldi/+ mice; thus, Cnot3ad-/- mice exhibit lipodystrophy.

Keywords: Cnot3; cold intolerance; lipodystrophy.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / metabolism
  • Animals
  • Disease Models, Animal
  • Epididymis / metabolism
  • Gene Expression Profiling
  • Glucose Intolerance / complications
  • Glucose Intolerance / metabolism
  • Hyperglycemia / complications
  • Hyperglycemia / metabolism
  • Hyperinsulinism / complications
  • Hyperinsulinism / metabolism
  • Inflammation / metabolism
  • Inflammation / pathology
  • Insulin Resistance
  • Lipodystrophy / metabolism*
  • Lipolysis
  • Male
  • Mice, Knockout
  • Organ Specificity
  • Thermogenesis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • CNOT3 protein, mouse
  • Transcription Factors