A lipid to treat non-alcoholic fatty liver disease – The dawn of ‘lipo-rehabilitation’?

• Published in: Journal of hepatology Vol. 56; no. 4; pp. 987 - 989
• Main Authors: Anstee, Q.M, Day, C.P
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.04.2012; Elsevier
• Subjects: Biological and medical sciences; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Insulin resistance; Liver. Biliary tract. Portal circulation. Exocrine pancreas; LRH-1; Medical sciences; Miscellaneous; NAFLD; NR5A2; Other diseases. Semiology; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Steatohepatitis; Insulin resistance; NAFLD; NR5A2; LRH-1; Steatohepatitis; Endocrinopathy; Metabolic diseases; Hepatic disease; Lipids; Target tissue resistance; Treatment; Non alcoholic steatohepatitis; Gastroenterology; Digestive diseases; Rehabilitation
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2011.10.002

Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl sidechains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatictriglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.