Skip to Content
MilliporeSigma
  • Mouse lipin-1 and lipin-2 cooperate to maintain glycerolipid homeostasis in liver and aging cerebellum.

Mouse lipin-1 and lipin-2 cooperate to maintain glycerolipid homeostasis in liver and aging cerebellum.

Proceedings of the National Academy of Sciences of the United States of America (2012-08-22)
Jennifer R Dwyer, Jimmy Donkor, Peixiang Zhang, Lauren S Csaki, Laurent Vergnes, Jessica M Lee, Jay Dewald, David N Brindley, Elisa Atti, Sotirios Tetradis, Yuko Yoshinaga, Pieter J De Jong, Loren G Fong, Stephen G Young, Karen Reue
ABSTRACT

The three lipin phosphatidate phosphatase (PAP) enzymes catalyze a step in glycerolipid biosynthesis, the conversion of phosphatidate to diacylglycerol. Lipin-1 is critical for lipid synthesis and homeostasis in adipose tissue, liver, muscle, and peripheral nerves. Little is known about the physiological role of lipin-2, the predominant lipin protein present in liver and the deficient gene product in the rare disorder Majeed syndrome. By using lipin-2-deficient mice, we uncovered a functional relationship between lipin-1 and lipin-2 that operates in a tissue-specific and age-dependent manner. In liver, lipin-2 deficiency led to a compensatory increase in hepatic lipin-1 protein and elevated PAP activity, which maintained lipid homeostasis under basal conditions, but led to diet-induced hepatic triglyceride accumulation. As lipin-2-deficient mice aged, they developed ataxia and impaired balance. This was associated with the combination of lipin-2 deficiency and an age-dependent reduction in cerebellar lipin-1 levels, resulting in altered cerebellar phospholipid composition. Similar to patients with Majeed syndrome, lipin-2-deficient mice developed anemia, but did not show evidence of osteomyelitis, suggesting that additional environmental or genetic components contribute to the bone abnormalities observed in patients. Combined lipin-1 and lipin-2 deficiency caused embryonic lethality. Our results reveal functional interactions between members of the lipin family in vivo, and a unique role for lipin-2 in central nervous system biology that may be particularly important with advancing age. Additionally, as has been observed in mice and humans with lipin-1 deficiency, the pathophysiology in lipin-2 deficiency is associated with dysregulation of lipid intermediates.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
5-Bromo-4-chloro-3-indolyl β-D-galactopyranoside, ≥98%
Sigma-Aldrich
5-Bromo-4-chloro-3-indolyl β-D-galactopyranoside, ≥98%, powder
Sigma-Aldrich
5-Bromo-4-chloro-3-indolyl β-D-galactopyranoside, tablet
Sigma-Aldrich
5-Bromo-4-chloro-3-indolyl β-D-galactopyranoside
Sigma-Aldrich
Anti-β-Actin antibody, Mouse monoclonal, clone AC-15, purified from hybridoma cell culture