RGD Reference Report - CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction. - Rat Genome Database

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CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction.

Authors: Peterson, Jonathan M  Wei, Zhikui  Seldin, Marcus M  Byerly, Mardi S  Aja, Susan  Wong, G William 
Citation: Peterson JM, etal., Am J Physiol Regul Integr Comp Physiol. 2013 Sep;305(5):R522-33. doi: 10.1152/ajpregu.00110.2013. Epub 2013 Jul 10.
RGD ID: 13507306
Pubmed: PMID:23842676   (View Abstract at PubMed)
PMCID: PMC3763026   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpregu.00110.2013   (Journal Full-text)

CTRP9 is a secreted multimeric protein of the C1q family and the closest paralog of the insulin-sensitizing adipokine, adiponectin. The metabolic function of this adipose tissue-derived plasma protein remains largely unknown. Here, we show that the circulating levels of CTRP9 are downregulated in diet-induced obese mice and upregulated upon refeeding. Overexpressing CTRP9 resulted in lean mice that dramatically resisted weight gain induced by a high-fat diet, largely through decreased food intake and increased basal metabolism. Enhanced fat oxidation in CTRP9 transgenic mice resulted from increases in skeletal muscle mitochondrial content, expression of enzymes involved in fatty acid oxidation (LCAD and MCAD), and chronic AMPK activation. Hepatic and skeletal muscle triglyceride levels were substantially decreased in transgenic mice. Consequently, CTRP9 transgenic mice had a greatly improved metabolic profile with markedly reduced fasting insulin and glucose levels. The high-fat diet-induced obesity, insulin resistance, and hepatic steatosis observed in wild-type mice were prevented in transgenic mice. Consistent with the in vivo data, recombinant protein significantly enhanced fat oxidation in L6 myotubes via AMPK activation and reduced lipid accumulation in H4IIE hepatocytes. Collectively, these data establish CTRP9 as a novel metabolic regulator and a new component of the metabolic network that links adipose tissue to lipid metabolism in skeletal muscle and liver.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
fatty acid oxidation acts_upstream_of_or_withinIDA 13507306PMID:23842676MGI 

Objects Annotated

Genes (Rattus norvegicus)
C1qtnf9  (C1q and TNF related 9)


Additional Information