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


CONCLUSIONS
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.
Berriel Diaz
Mauricio
M
Emmy Noether and Marie Curie Research Group, Molecular Metabolic Control, German Cancer Research Center Heidelberg, Heidelberg, Germany.
Krones-Herzig
Anja
A
Metzger
Dagmar
D
Ziegler
Anja
A
Vegiopoulos
Alexandros
A
Klingenspor
Martin
M
Müller-Decker
Karin
K
Herzig
Stephan
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002100:Cachexia / Q000378:metabolism* / Q000503:physiopathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000503:physiopathology; D002460:Cell Line; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D034622:RNA Interference; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D014280:Triglycerides