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Obesity‐associated increases in acute phase protein expression and additive effects of leptin

Inflammation is key in obesity‐associated cardiovascular disease (CVD) development. The obese have higher serum leptin (an inflammatory factor) and the acute phase factors C‐reactive protein (CRP) and serum amyloid A (SAA) than lean counterparts. We hypothesized that obesity‐associated increases in leptin levels increase CRP and SAA expression by using diet‐induced obese (DIO; 60% fat diet) and lean (10% fat diet) mice. We found increased serum CRP, SAA, and leptin in DIO than lean mice. Next, we tested whether leptin deficient obese (ob/ob) mice had increased CRP and SAA levels, and whether leptin further increased concentrations of these proteins. Ob/ob mice had increased serum CRP and SAA concentrations compared to lean mice; leptin administration to ob/ob mice further increased CRP and SAA concentrations in ob/ob mice over saline‐injected ob/ob mice (P<0.05). To find the mechanism of CRP/SAA increases, we measured serum IL‐1B and IL‐6 and found leptin does not increase these levels, but leptin increased hepatic CRP, SAA, and leptin signaling intermediates (JAK‐2). Increased CVD risk in obesity may be mediated by direct upregulation of CRP and SAA by leptin.