title: CTRP3 attenuates diet-induced hepatic steatosis by regulating triglyceride metabolism.
abstract: CTRP3 is a secreted plasma protein of the C1q family that helps regulate hepatic gluconeogenesis and is downregulated in a diet-induced obese state. However, the role of CTRP3 in regulating lipid metabolism has not been established. Here, we used a transgenic mouse model to address the potential function of CTRP3 in ameliorating high-fat diet-induced metabolic stress. Both transgenic and wild-type mice fed a high-fat diet showed similar body weight gain, food intake, and energy expenditure. Despite similar adiposity to wild-type mice upon diet-induced obesity (DIO), CTRP3 transgenic mice were strikingly resistant to the development of hepatic steatosis, had reduced serum TNF-α levels, and demonstrated a modest improvement in systemic insulin sensitivity. Additionally, reduced hepatic triglyceride levels were due to decreased expression of enzymes (GPAT, AGPAT, and DGAT) involved in triglyceride synthesis. Importantly, short-term daily administration of recombinant CTRP3 to DIO mice for 5 days was sufficient to improve the fatty liver phenotype, evident as reduced hepatic triglyceride content and expression of triglyceride synthesis genes. Consistent with a direct effect on liver cells, recombinant CTRP3 treatment reduced fatty acid synthesis and neutral lipid accumulation in cultured rat H4IIE hepatocytes. Together, these results establish a novel role for CTRP3 hormone in regulating hepatic lipid metabolism and highlight its protective function and therapeutic potential in attenuating hepatic steatosis.
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Peterson
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Seldin
authors.forename: Zhikui
authors.initials: Z
authors.lastname: Wei
authors.forename: Susan
authors.initials: S
authors.lastname: Aja
authors.forename: G William
authors.initials: GW
authors.lastname: Wong
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D059305:Diet, High-Fat; D005227:Fatty Acids / Q000096:biosynthesis; D005234:Fatty Liver / Q000209:etiology* / Q000517:prevention & control*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014280:Triglycerides / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D054392:Adipokines; C428135:CORS26 protein, mouse; D005227:Fatty Acids; D011994:Recombinant Proteins; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha
keywords: C1q/TNF; CTRP; NAFLD; adipokine; fatty liver; hepatic steatosis; triglyceride synthesis