Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: Role of autophagy

Guo, Rui; Zhang, Yingmei; Turdi, Subat; Ren, Jun

doi:10.1016/j.bbadis.2013.03.013

Cited by 147 publications

(115 citation statements)

References 63 publications

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“…Other studies have shown increased weight gain in response to HF diet for 22 weeks, 23 we think that the difference in results can be attributed to the shorter 12-week duration of our study. This duration of 12 weeks of high fat diet decreased adiponectin mRNA in adipose tissue of WT mice.…”

Section: Discussioncontrasting

confidence: 46%

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Is the lack of adiponectin associated with increased ER/SR stress and inflammation in the heart?

et al. 2013

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Objective: To study whether there is an association between adiponectin and endoplasmic reticulum/sarcoplasmic reticulum (eRsR) stress.Research design: eleven-month-old male wild-type (WT) and adiponectin knockout (ADKO) mice were placed on chow or high fat diet for 12 weeks. The changes in eR stress and inflammatory genes were determined in the epididymal adipose, as well as heart tissue of adult WT and ADKO mice. To understand the role of eR/sR stress in the regulation of adiponectin, we studied the effect of tunicamycin or palmitate on h9c2 cardiomyoblasts in culture. To demonstrate the protective role of adiponectin, we studied the effect of purified adiponectin on the regulation of eRsR stress genes and inflammation in h9c2 cardiomyoblasts.Results: (1) high fat diet increased TNFα in adipose tissue of ADKO mice. (2) eRsR stress genes, hsPa5, eRN1, and GADD34, and inflammation response genes, TNFα and cD68, were increased in heart of ADKO mice. high fat diet did not further increase the effect. (3) Induction of eRsR stress by tunicamycin in h9c2 resulted in the upregulation of eRsR stress response genes along with downregulation of adiponectin, adiponectin receptors 1 and 2, and serca2A. eR stress was accompanied by down regulation of Iκβα and an increase in hsPa5 proteins. (4) Adiponectin decreased eRsR stress and inflammation response genes and increased serca2A in to h9c2 cardiomyoblasts. Conclusion:The lack of adiponectin is associated with increased eR/sR stress and inflammation in the heart. Adiponectin provides a protective effect by lowering inflammation and eR/sR stress along with increasing serca2A in h9c2 cells.

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Section: Discussioncontrasting

confidence: 46%

“…This duration of 12 weeks of high fat diet decreased adiponectin mRNA in adipose tissue of WT mice. The animals used in the earlier study were 4 mo of age 23 ; we have compared 11-mo-old WT and ADKO mice.…”

Section: Discussionmentioning

confidence: 99%

Is the lack of adiponectin associated with increased ER/SR stress and inflammation in the heart?

et al. 2013

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“…However, in the presence of an additional stress such as ischemia and reperfusion (I/R), high fat-fed hearts become more prone to cardiac injury due to impaired autophagy ( 15 ). In the long-term, HFD mice eventually develop contractile dysfunction in parallel with impaired autophagy ( 41 ). These data suggest that impairment in autophagic turnover may heighten sensitivity to stress and may progressively contribute to contractile dysfunction in diet-induced obesity.…”

Section: Pkc ␤ Regulates Nox2-activity In Palmitate-treated Cmsmentioning

confidence: 80%

Lipid-induced NOX2 activation inhibits autophagic flux by impairing lysosomal enzyme activity

Jaishy

Zhang

Chung

et al. 2015

Journal of Lipid Research

101

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This article is available online at http://www.jlr.org deposition of toxic lipid intermediates in the heart that may have deleterious effects ("lipotoxicity") on myocardial structure and function ( 2 ). Studies using mouse models of increased myocardial lipid availability showed that increasing lipid accumulation directly in cardiomyocytes (CMs) was suffi cient to induce lipotoxic cardiomyopathy and premature cell death independently of systemic or neurohumoral effects of obesity ( 3-5 ). However, gaps remain in our mechanistic understanding of the interactions between lipid accumulation and cardiac dysfunction and the impact of lipotoxicity on cardiac autophagy has been relatively understudied.Macroautophagy (hereafter "autophagy") is a catabolic process wherein cytoplasmic materials are delivered to lysosomes in double-membrane structures called autophagosomes for degradation ( 6 ). Autophagy regulates lipid metabolism in multiple tissues ( 7-9 ). Impaired autophagy Abstract Autophagy is a catabolic process involved in maintaining energy and organelle homeostasis. The relationship between obesity and the regulation of autophagy is cell type specifi c. Despite adverse consequences of obesity on cardiac structure and function, the contribution of altered cardiac autophagy in response to fatty acid overload is incompletely understood. Here, we report the suppression of autophagosome clearance and the activation of NADPH oxidase (Nox)2 in both high fat-fed murine hearts and palmitate-treated H9C2 cardiomyocytes (CMs). Defective autophagosome clearance is secondary to superoxidedependent impairment of lysosomal acidifi cation and enzyme activity in palmitate-treated CMs. Inhibition of Nox2 prevented superoxide overproduction, restored lysosome acidifi cation and enzyme activity, and reduced autophagosome accumulation in palmitate-treated CMs. Palmitate-induced Nox2 activation was dependent on the activation of classical protein kinase Cs (PKCs), specifi cally PKC ␤ II. These fi ndings reveal a novel mechanism linking lipotoxicity with a PKC ␤ -Nox2-mediated impairment in pH-dependent lysosomal enzyme activity that diminishes autophagic turnover in CMs. Obesity is an independent risk factor for CVD ( 1 ). A prominent factor in obesity-related cardiomyopathy is the ectopic

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“…As cardiac hypertrophy is an important feature of diabetic cardiomyopathy (DCM) (Nunes et al 2013), we speculate that perigestational exposure to HFA may program female progeny to develop DCM, increasing the risk of heart failure (Boudina & Abel 2010, Nunes et al 2013. Strikingly, hyperglycemia (Murarka & Movahed 2010), hyperinsulinemia (Boudina & Abel 2010, Murarka & Movahed 2010, and adiponectin deficiency (Guo et al 2013), all manifested in HFA female offspring, have been suggested to contribute to cardiac hypertrophy (Guo et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Excess perigestational folic acid exposure induces metabolic dysfunction in post-natal life

Keating¹,

Correia-Branco²,

Araújo³

et al. 2015

Journal of Endocrinology

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The aim of this study was to understand whether high folic acid (HFA) exposure during the perigestational period induces metabolic dysfunction in the offspring, later in life. To do this, female Sprague-Dawley rats (G0) were administered a dose of folic acid (FA) recommended for pregnancy (control, C, 2 mg FA/kg of diet, nZ5) or a high dose of FA (HFA, 40 mg FA/kg of diet, nZ5). Supplementation began at mating and lasted throughout pregnancy and lactation. Body weight and food and fluid intake were monitored in G0 and their offspring (G1) till G1 were 13 months of age. Metabolic blood profiles were assessed in G1 at 3 and 13 months of age (3M and 13M respectively). Both G0 and G1 HFA females had increased body weight gain when compared with controls, particularly 22 (G0) and 10 (G1) weeks after FA supplementation had been stopped. G1 female offspring of HFA mothers had increased glycemia at 3M, and both female and male G1 offspring of HFA mothers had decreased glucose tolerance at 13M, when compared with matched controls. At 13M, G1 female offspring of HFA mothers had increased insulin and decreased adiponectin levels, and G1 male offspring of HFA mothers had increased levels of leptin, when compared with matched controls. In addition, feeding of fructose to adult offspring revealed that perigestational exposure to HFA renders female progeny more susceptible to developing metabolic unbalance upon such a challenge. The results of this work indicate that perigestational HFA exposure the affects long-term metabolic phenotype of the offspring, predisposing them to an insulin-resistant state.

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Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: Role of autophagy

Cited by 147 publications

References 63 publications

Is the lack of adiponectin associated with increased ER/SR stress and inflammation in the heart?

Is the lack of adiponectin associated with increased ER/SR stress and inflammation in the heart?

Lipid-induced NOX2 activation inhibits autophagic flux by impairing lysosomal enzyme activity

Excess perigestational folic acid exposure induces metabolic dysfunction in post-natal life

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