Abstract 3776: IL-6 Deficient Mice are Protected from Diet-Induced Inflammation and Insulin Resistance in Heart
Circulating levels of inflammatory cytokines are elevated in obesity, and IL-6 is shown to regulate glucose metabolism in peripheral organs. Our recent study found that IL-6 reduces myocardial glucose metabolism by suppressing AMPK. In this report, IL-6 deficient (IL-6 KO) mice were examined to investigate the role of inflammation in heart. Since IL-6 KO mice are more prone to develop obesity, high-fat diet (HFD; 55% fat) was administered shortly after weaning for 3 wks, and myocardial glucose metabolism was measured during hyperinsulinemic-euglycemic clamp combined with 2-[14C]deoxyglucose in awake IL-6 KO and wild-type (WT) mice (n=7). Whole body fat mass, measured using 1H-MRS, was similarly increased in IL-6 KO (1.9±0.1 g to 3.8±0.2 g) and WT mice (2.2±0.3 g to 4.4±0.5 g) after 3 weeks of HFD. Insulin-stimulated glucose uptake in heart was increased in HFD-fed IL-6 KO mice compared to HFD-fed WT mice (Fig. 1⇓; *P<0.05). We have recently found that HFD caused cardiac inflammation, and IL-6 deficiency attenuated diet-induced cardiac inflammation and reduced macrophage-specific CD68 levels in heart (Fig. 2⇓). Cardiomyocyte SOCS3 levels were also reduced in HFD-fed IL-6 KO mice (Fig. 3⇓). We performed echocardiography to assess cardiac function and structure in mice after 11 weeks of HFD (n=6). IL-6 KO mice showed improved ventricular fractional shortening (Fig. 4⇓) and lower left ventricular posterior wall thickness as compared to the WT mice. These results demonstrate that IL-6 deficiency attenuates HFD-induced cardiac inflammation and increases myocardial glucose metabolism. Our findings underscore the important role of IL-6 on cardiac inflammation and metabolism in obesity.