Nuclear receptor cofactor receptor interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice

• Published in: Hepatology (Baltimore, Md.) Vol. 48; no. 3; pp. 782 - 791
• Main Authors: Diaz, Mauricio Berriel, Krones‐Herzig, Anja, Metzger, Dagmar, Ziegler, Anja, Vegiopoulos, Alexandros, Klingenspor, Martin, Müller‐Decker, Karin, Herzig, Stephan
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-09-2008; Wiley
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Biological and medical sciences; Cachexia - metabolism; Cachexia - physiopathology; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - physiopathology; Cell Line; Cells, Cultured; Disease Models, Animal; Energy Metabolism - physiology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation; Homeostasis - physiology; Humans; Lipid Metabolism - physiology; Liver - metabolism; Liver - microbiology; Liver - physiopathology; Liver Neoplasms - metabolism; Liver Neoplasms - physiopathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Mice; Mice, Inbred C57BL; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; RNA Interference; Sepsis - metabolism; Sepsis - physiopathology; Transfection; Triglycerides - metabolism; Vertebrata; Nuclear receptor; Mammalia; Mouse; Animal; Liver; Rodentia; Gastroenterology; Receptor protein; Metabolism; Triglyceride; Cofactor
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.22383

In mammals, triglycerides (TG) represent the most concentrated form of energy. Aberrant TG storage and availability are intimately linked to the negative energy balance under severe clinical conditions, such as starvation, sepsis, or cancer cachexia. Despite its crucial role for energy homeostasis, molecular key determinants of TG metabolism remain enigmatic. Here we show that the expression of nuclear receptor cofactor receptor interacting protein (RIP) 140 was induced in livers of starved, septic, and tumor‐bearing mice. Liver‐specific knockdown of RIP140 led to increased hepatic TG release and alleviated hepatic steatosis in tumor‐bearing, cachectic animals. Indeed, hepatic RIP140 was found to control the expression of lipid‐metabolizing genes in liver. Conclusion: By preventing the mobilization of hepatic TG stores, the induction of RIP140 in liver provides a molecular rationale for hepatic steatosis in starvation, sepsis, or cancer cachexia. Inhibition of hepatic RIP140 transcriptional activity might, thereby, provide an attractive adjunct scheme in the treatment of these conditions. (HEPATOLOGY 2008.)