The Lipin family of nuclear proteins contains three members: Lipin-1, Lipin-2 and Lipin-3, all of which contain a nuclear signal sequence, a highly conserved amino-terminal (NLIP) domain and a carboxy-terminal (CLIP) domain. LPIN1 (Lipin-1) is crucial for normal adipose tissue development and metabolism. LPIN1 selectively activates a subset of PGC-1á target pathways, including fatty acid oxidation and mitochondrial oxidative phosphorylation by inducing expression of the nuclear receptor PPARá. LPIN1 also inactivates the lipogenic program and suppresses circulating lipid levels. An abundance of LPIN1 promotes fat accumulation and insulin sensitivity, whereas a deficiency in LPIN1 may deter normal adipose tissue development, resulting in insulin resistance and lipodystrophy, a heterogeneous group of disorders characterized by loss of body fat, fatty liver, hypertriglyceridemia and insulin resistance.
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