Involvement of adipokines in rimonabant-mediated insulin sensitivity in ob/ob mice.
OBJECTIVE
It has been recently reported that blockade of type 1 cannabinoid (CB1) receptors by specific antagonists or genetic manipulation alleviates dyslipidaemia, hyperglycaemia and insulin resistance in animal models of obesity and type 2 diabetes. However, the precise role of adipokines in the insulin-sensitising effects of the CB1 antagonist rimonabant is not clear.


METHODS
ob/ob mice were treated with different doses of rimonabant and then subjected to an oral glucose tolerance test. The expression of different adipokines in white adipose tissue was analysed by quantitative real-time PCR.


RESULTS
Rimonabant (30 mg/kg) significantly inhibited body weight and fat pad weight gain (P < 0.05) and improved glucose tolerance. Gene expression analysis indicated that tumour necrosis factor-alpha, visfatin and retinol binding protein-4 were downregulated in the adipose tissue of ob/ob mice treated with rimonabant compared with controls, whereas adiponectin was significantly upregulated.


CONCLUSIONS
Rimonabant-mediated alteration of adipokines in white adipose tissues may play a role in improving insulin sensitivity in obese animals.
Mohapatra
Jogeswar
J
Zydus Research Centre, Moraiya, Ahmedabad, Gujarat, India.
Sharma
Manoranjan
M
Singh
Satinder
S
Pandya
Gaurav
G
Chatterjee
Abhijit
A
Balaraman
Ramachandran
R
Patel
Pankaj R
PR
Jain
Mukul R
MR
D054392:Adipokines / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy*; D009929:Organ Size / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077285:Rimonabant; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D054392:Adipokines; D052242:Adiponectin; D019440:Anti-Obesity Agents; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; C502487:Rbp4 protein, mouse; D043884:Receptor, Cannabinoid, CB1; D054839:Retinol-Binding Proteins, Plasma; D014409:Tumor Necrosis Factor-alpha; D054409:Nicotinamide Phosphoribosyltransferase; D000077285:Rimonabant