title: Therapeutic strategies for metabolic diseases: Small-molecule diacylglycerol acyltransferase (DGAT) inhibitors.
abstract: Metabolic diseases such as atherogenic dyslipidemia, hepatic steatosis, obesity, and type II diabetes are emerging as major global health problems. Acyl-CoA:diacylglycerol acyltransferase (DGAT) is responsible for catalyzing the final reaction in the glycerol phosphate pathway of triglycerol synthesis. It has two isoforms, DGAT-1 and DGAT-2, which are widely expressed and present in white adipose tissue. DGAT-1 is most highly expressed in the small intestine, whereas DGAT-2 is primarily expressed in the liver. Therefore, the selective inhibition of DGAT-1 has become an attractive target with growing potential for the treatment of obesity and type II diabetes. Furthermore, DGAT-2 has been suggested as a new target for the treatment of DGAT-2-related liver diseases including hepatic steatosis, hepatic injury, and fibrosis. In view the discovery of drugs that target DGAT, herein we attempt to provide insight into the scope and further reasons for optimization of DGAT inhibitors.
authors: BK21Plus R-FIND Team, College of Pharmacy, Dongguk University Seoul, 32 Dongguk-ro, Ilsandong-gu, Koyang 410-820 (Republic of Korea).
authors: Ravi
authors: R
authors: Naik
authors: Brice W
authors: BW
authors: Obiang-Obounou
authors: Minkyoung
authors: M
authors: Kim
authors: Yongseok
authors: Y
authors: Choi
authors: Hyun Sun
authors: HS
authors: Lee
authors: Kyeong
authors: K
authors: Lee
mesh_terms: D001688:Biological Products / Q000627:therapeutic use; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy*; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D001688:Biological Products; D004791:Enzyme Inhibitors; D014280:Triglycerides; D051048:Diacylglycerol O-Acyltransferase
keywords: DGAT; diacylglycerol acyltransferase; metabolic disorders; small-molecule inhibitors; triacylglycerides