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

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