Linked Life Data

20952387

Source:http://linkedlifedata.com/resource/pubmed/id/20952387

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2010-12-14
pubmed:databankReference
pubmed:abstractText
Adipose tissue-derived adipokines play important roles in controlling systemic insulin sensitivity and energy balance. Our recent efforts to identify novel metabolic mediators produced by adipose tissue have led to the discovery of a highly conserved family of secreted proteins, designated as C1q/TNF-related proteins 1-10 (CTRP1 to -10). However, physiological functions regulated by CTRPs are largely unknown. Here we provide the first in vivo functional characterization of CTRP3. We show that circulating levels of CTRP3 are inversely correlated with leptin levels; CTRP3 increases with fasting, decreases in diet-induced obese mice with high leptin levels, and increases in leptin-deficient ob/ob mice. A modest 3-fold elevation of plasma CTRP3 levels by recombinant protein administration is sufficient to lower glucose levels in normal and insulin-resistant ob/ob mice, without altering insulin or adiponectin levels. The glucose-lowering effect in mice is linked to activation of the Akt signaling pathway in liver and a marked suppression of hepatic gluconeogenic gene expression. Consistent with its effects in mice, CTRP3 acts directly and independently of insulin to regulate gluconeogenesis in cultured hepatocytes. In humans, alternative splicing generates two circulating CTRP3 isoforms differing in size and glycosylation pattern. The two human proteins form hetero-oligomers, an association that does not require interdisulfide bond formation and appears to protect the longer isoform from proteolytic cleavage. Recombinant human CTRP3 also reduces glucose output in hepatocytes by suppressing gluconeogenic enzyme expression. This study provides the first functional evidence linking CTRP3 to hepatic glucose metabolism and establishes CTRP3 as a novel adipokine.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39691-701
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20952387-Adipokines, pubmed-meshheading:20952387-Adiponectin, pubmed-meshheading:20952387-Alternative Splicing, pubmed-meshheading:20952387-Animals, pubmed-meshheading:20952387-Base Sequence, pubmed-meshheading:20952387-Blood Glucose, pubmed-meshheading:20952387-Cell Line, Tumor, pubmed-meshheading:20952387-Fasting, pubmed-meshheading:20952387-Gluconeogenesis, pubmed-meshheading:20952387-HEK293 Cells, pubmed-meshheading:20952387-Hepatocytes, pubmed-meshheading:20952387-Humans, pubmed-meshheading:20952387-Insulin, pubmed-meshheading:20952387-Leptin, pubmed-meshheading:20952387-Liver, pubmed-meshheading:20952387-Mice, pubmed-meshheading:20952387-Mice, Obese, pubmed-meshheading:20952387-Molecular Sequence Data, pubmed-meshheading:20952387-Protein Isoforms, pubmed-meshheading:20952387-Rats, pubmed-meshheading:20952387-Tumor Necrosis Factors
pubmed:year
2010
pubmed:articleTitle
C1q/TNF-related protein-3 (CTRP3), a novel adipokine that regulates hepatic glucose output.
pubmed:affiliation
Department of Physiology and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural