Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action.
Central (visceral) obesity is more closely associated with insulin resistance, type 2 diabetes, and cardiovascular disease than is peripheral [subcutaneous (sc)] obesity, but the underlying mechanism for this pathophysiological difference is largely unknown. To understand the molecular basis of this difference, we sequenced 10,437 expressed sequence tags (ESTs) from a human omental fat cDNA library and discovered a novel visceral fat depot-specific secretory protein, which we have named omentin. Omentin ESTs were more abundant than many known adipose genes, such as perilipin, adiponectin, and leptin in the cDNA library. Protein sequence analysis indicated that omentin mRNA encodes a peptide of 313 amino acids, containing a secretory signal sequence and a fibrinogen-related domain. Northern analysis demonstrated that omentin mRNA was predominantly expressed in visceral adipose tissue and was barely detectable in sc fat depots in humans and rhesus monkeys. Quantative real-time PCR showed that omentin mRNA was expressed in stromal vascular cells, but not fat cells, isolated from omental adipose tissue, with >150-fold less in sc cell fractions. Accordingly, omentin protein was secreted into the culture medium of omental, but not sc, fat explants. Omentin was detectable in human serum by Western blot analysis. Addition of recombinant omentin in vitro did not affect basal but enhanced insulin-stimulated glucose uptake in both sc (47%, n = 9, P = 0.003) and omental (approximately 30%, n = 3, P < 0.05) human adipocytes. Omentin increased Akt phosphorylation in the absence and presence of insulin. In conclusion, omentin is a new adipokine that is expressed in omental adipose tissue in humans and may regulate insulin action.
Yang
Rong-Ze
RZ
Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Lee
Mi-Jeong
MJ
Hu
Hong
H
Pray
Jessica
J
Wu
Hai-Bin
HB
Hansen
Barbara C
BC
Shuldiner
Alan R
AR
Fried
Susan K
SK
McLenithan
John C
JC
Gong
Da-Wei
DW
D000273:Adipose Tissue / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D020224:Expressed Sequence Tags; D058851:GPI-Linked Proteins; D051246:Glucose Transport Proteins, Facilitative; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D037102:Lectins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt; D017154:Stromal Cells / Q000378:metabolism
D016207:Cytokines; D058851:GPI-Linked Proteins; D051246:Glucose Transport Proteins, Facilitative; C432397:ITLN1 protein, human; D007328:Insulin; D037102:Lectins; D051057:Proto-Oncogene Proteins c-akt