Adipocyte-specific disruption of mouse Cnot3 causes lipodystrophy.

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.