Overexpression of visfatin/PBEF/Nampt alters whole-body insulin sensitivity and lipid profile in rats.
BACKGROUND
Visfatin/PBEF/Nampt is an adipose-derived hormone proposed to exert insulin-mimicking effects and play a positive role in attenuating insulin resistance. However, the precise mechanisms underlying the beneficial effects of visfatin/PBEF/Nampt on insulin sensitivity remain unknown.


METHODS
Euglycemic-hyperinsulinemic clamps were used in the same groups of rats to study the in vivo effect of visfatin/PBEF/Nampt on insulin sensitivity and glucose/lipid metabolism before and after the overexpression of visfatin/PBEF/Nampt protein, which was carried out by injection of pcDNA3.1-visfatin plasmid.


RESULTS
On day 4 after plasmid injection, plasma visfatin/PBEF/Nampt protein levels were significantly increased and displayed a hypocholesterolemic effect in both normal-chow (NC) and high-fat diet (HT) animals with pcDNA3.1-visfatin treatment. A second glucose clamp also demonstrated increased insulin sensitivity in pcDNA3.1-visfatin animals. Consistent with the clamp data, the extent of insulin receptor substrate (IRS)-1 tyrosine phosphorylation in response to insulin was significantly enhanced in the liver and adipose tissues. In addition, the mRNA expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) and sterol regulatory element-binding proteins 2 (SREBP-2) in the liver and adipose tissues was also significantly upregulated in these animals.


CONCLUSIONS
These results demonstrate that visfatin/PBEF/Nampt improves insulin sensitivity and exerts its hypocholesterolemic effects at least partially through upregulation of the tyrosine phosphorylation of IRS-1 protein and the mRNA levels of PPARgamma and SREBP-2.
Sun
Qin
Q
Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Li
Ling
L
Li
Renzhe
R
Yang
Mengliu
M
Liu
Hua
H
Nowicki
Michael J
MJ
Zong
Haihong
H
Xu
Jun
J
Yang
Gangyi
G
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism
D016207:Cytokines; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D047495:PPAR gamma; D012333:RNA, Messenger; C470194:Srebf2 protein, rat; D051779:Sterol Regulatory Element Binding Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D054409:Nicotinamide Phosphoribosyltransferase; C504970:nicotinamide phosphoribosyltransferase, rat; D005947:Glucose