GPAT4 ENCODES A MAMMALIAN, MICROSOMAL ACYL-COA:GLYCEROL 3-PHOSPHATE ACYLTRANSFERASE

摘要

The present invention provides isolated and purified polynucleotides and polypeptides related to mouse and human microsomal acyl-CoA: glycerol 3-phosphate acyltransferase 4 (GP AT4) and their uses in modulating triacylglycerol (TAG) levels in a cell or sample of interest. The invention also provides GPAT4 agonists and antagonists, e.g., GPAT4 polynucleotides and polypeptides, antibodies to GPAT4 (agonistic and antagonistic antibodies), GPAT4 inhibitory polypeptides, and GPAT4 inhibitory polynucleotides. The present invention is also directed to novel methods for diagnosing, prognosing, monitoring, treating, ameliorating and/or preventing conditions related to GPAT4, TAG synthesis (or accumulation), or the synthesis (or accumulation) of TAG precursors (e.g., MAG, LPA, PA, and/or G3P). These GPAT4-associated conditions include, but are not limited to, dyslipidemia (e.g., hyperlipidemia, hypertriglyceridemia, Type III hyperlipidemia), obesity, hypercholesterolemia, hepatic steatosis, cancer, skin disorders associated with altered lipid metabolism (e.g., acne vulgaris, dry skin), adiposity, type 2 diabetes (and complications associated therewith, such as dermopathy, retinopathy, neuropathy, and nephropathy), insulin resistance, hyperinsulinemia, hypertension, cardiovascular disease, atherosclerosis, stroke, thrombosis, lipodystrophy, lipopenia, Reye's syndrome, Cushing's syndrome, metabolic syndrome (e.g., syndrome X), eating disorders (e.g., anorexia, bulimia), skin homeostasis, disorders related to energy storage, nutrient absorption, and lipid metabolism, reduced or absent lactation, and low preterm birth weight (and complications thereof, such as defects in neural development).