Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism

OBJECTIVE: Insulin resistance (IR) was reported to be associated with chronic heart failure (CHF). Adiponectin, an insulin-sensitizing hormone with anti-inflammatory activity, improves energy metabolism via AMP-activated protein kinase (AMPK). AMPK deficiency is associated with depressed cardiac function under stress conditions. However, it is not clear whether adiponectin plays an important role in CHF. We hypothesize that deficiency of adiponectin might result in deterioration of heart failure. METHODS: Using adiponectin null mice and their littermates, we examined the effects of adiponectin on LV pressure overload-induced cardiac hypertrophy and failure, and investigated the mechanisms involved. RESULTS: Three weeks after transverse aortic constriction (TAC), cardiac hypertrophy (evaluated from the heart-to-body weight ratio: 7.62+/-0.27 in wild-type (WT) mice, 9.97+/-1.13 in knockout (KO) mice, P<0.05) and pulmonary congestion (lung-to-body weight ratio: 9.05+/-1.49 in WT mice, 14.95+/-2.36 in KO mice, P<0.05) were significantly greater in adiponectin KO mice than WT mice. LV dimensions were also increased in KO mice. Compared with WT TAC mice, expression of AMPKalpha protein was lower, while IR was higher in KO TAC mice. CONCLUSION: These findings indicate that adiponectin deficiency leads to progressive cardiac remodeling in pressure overloaded condition mediated via lowing AMPK signaling and impaired glucose metabolism.