Resistin is an adipose-derived hormone that has been proposed as a link among 
obesity, insulin resistance, and diabetes. In agreement with a role of resistin 
in insulin resistance, the administration of recombinant resistin led to glucose 
intolerance in mice and impaired insulin action in rat liver. However, the 
regulation of resistin expression by physiological conditions, hormones, or 
agents known to modulate insulin sensitivity does not always support the 
association between resistin and obesity-induced insulin resistance. In the 
present study we investigated the effects of leptin administration on adipose 
resistin expression in insulin-resistant and obese ob/ob mice. We show that the 
expression of resistin mRNA and protein in adipose tissue is lower in ob/ob than 
in wild-type control mice, in agreement with the reduced adipocyte resistin mRNA 
level reported in several models of obesity. Leptin administration in ob/ob mice 
resulted in improvement of insulin sensitivity concomitant with a decrease in 
resistin gene expression. The lack of effect of leptin on resistin in db/db mice 
indicated that the leptin inhibitory action on resistin expression requires the 
long leptin receptor isoform. In addition, we demonstrated that the effect of 
leptin on resistin expression was centrally mediated. High-fat feeding in 
C57BL/6J wild-type mice, which is known to induce the development of obesity and 
insulin resistance, produced an increase in resistin expression. Interestingly, 
in both ob/ob and high fat-fed mice we obtained a striking positive correlation 
between glycemia and resistin gene expression. In conclusion, our results 
demonstrate that leptin decreases resistin expression and suggest that resistin 
may influence glucose homeostasis.