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.


CONCLUSIONS
These findings indicate that adiponectin deficiency leads to progressive cardiac remodeling in pressure overloaded condition mediated via lowing AMPK signaling and impaired glucose metabolism.
Liao
Yulin
Y
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Takashima
Seiji
S
Maeda
Norikazu
N
Ouchi
Noriyuki
N
Komamura
Kazuo
K
Shimomura
Iichiro
I
Hori
Masatsugu
M
Matsuzawa
Yuji
Y
Funahashi
Tohru
T
Kitakaze
Masafumi
M
D000263:Adenylate Kinase / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D004452:Echocardiography; D005215:Fasting; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*
D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D000263:Adenylate Kinase