Copyright © 2005, European Society of Cardiology
Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism
aDepartment of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
bDepartment of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
cCardiovascular Division of Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
* Corresponding author. Tel.: +81 6 6833 5012x2225; fax: +81 6 6836 1120. Email address: kitakaze{at}zf6.so-net.ne.jp
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 AMPK
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.
KEYWORDS Adiponectin; Heart failure; Myocardial hypertrophy; Metabolic syndrome
Time for primary review 24 days
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