The role of lipin 1 in adipogenesis and lipid metabolism.

In conditions such as obesity and lipodystrophy, insulin resistance and diabetes are associated with the dysregulation of lipid metabolism in adipose tissue, skeletal muscle and liver. One factor that influences lipid homeostasis in all three of these tissues is lipin 1. Studies in mouse models and humans have established a relationship between lipin 1 levels and both triglyceride storage in adipose tissue and insulin sensitivity. Thus, lipin 1 deficiency in the mouse results in lipodystrophy and insulin resistance. In contrast, fat-specific expression of a lipin 1 transgene results in increased triglyceride storage in adipose tissue and insulin sensitivity, despite the development of obesity. In humans, lipin 1 expression levels in adipose tissue are positively correlated with insulin sensitivity, and inversely correlated with inflammatory cytokine expression and intramyocellular lipid, a key marker of insulin resistance. These data from mouse and human studies suggest a role for lipin 1 in directing lipid to the appropriate storage site in adipose tissue, thus potentially reducing lipid accumulation in tissues such as muscle and liver. The mechanism of lipin 1 action appears to be complex, with evidence for roles in triglyceride biosynthesis and in the regulation of gene expression.