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The circulating concentrations of adiponectin, an antidiabetic adipokine, have been shown to be reduced in obesity, in relation to an increase in inflammation. The aim of the present work was to assess the effect of leptin replacement on adiponectin levels and expression as well as on markers of oxidative stress and inflammation in leptin-deficient  ob/ob  mice. Twelve-week-old male mice (n = 7–10 per group) were treated with either saline (wild type and  ob/ob  mice) or leptin ( ob/ob  mice) for 18 days. A third group of  ob/ob  mice was treated with saline and pair-fed to the amount of food consumed by the leptin-treated group. Leptin replacement restored values of adiponectin ( P  < 0.001), reduced circulating 8-isoprostane and serum amyloid A (SAA) levels ( P  < 0.05 for both), and significantly downregulated the increased gene expression of osteopontin ( Spp1 ,  P  < 0.05),  Saa3  ( P  < 0.05),  Cd68  ( P  < 0.01),  Il6  ( P  < 0.01) and NADPH oxidase ( Nox1  and  Nox2 ,  P  < 0.01) in the perirenal WAT and  Spp1  ( P  < 0.05) in the liver of  ob/ob  mice. In cultured adipocytes from  ob/ob  mice, leptin increased ( P  < 0.05) the mRNA expression and secretion of adiponectin. We concluded that circulating concentrations of adiponectin are positively regulated by leptin and ameliorate obesity-associated oxidative stress and inflammation in mice.

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Normalization of adiponectin concentrations by leptin replacement in ob/ob mice is accompanied by reductions in systemic oxidative stress and inflammation