Gender differences in adiponectin modulation of cardiac remodeling in mice deficient in endothelial nitric oxide synthase

Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte‐derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso‐protective, anti‐inflammatory, and anti‐atherogenic properties. We hypothesized that increased levels of adiponectin would alleviate cardiac pathology resulting from eNOS deficiency, while decreased levels of adiponectin would exacerbate the pathology. Male and female mice, deficient in eNOS, and either lacking or over‐expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac magnetic resonance imaging was performed to serially assess heart morphology and function up to 40 weeks of age. Thirty‐two weeks of HFD feeding led to significantly greater LV mass in male mice deficient in eNOS and either lacking or over‐expressing adiponectin. Heart function was significantly reduced when the mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for female mice, heart function was only reduced when both eNOS and adiponectin were lacking. Thus, while over‐expression of adiponectin in the eNOS deficient HFD fed male mice preserved function at the expense of significantly increased LV mass, female mice were protected from decreased function and increased LVH by over‐expression of adiponectin. Our results demonstrate a sexual dimorphism in response of the heart to alterations in eNOS and adiponectin during high fat feeding and suggest that adiponectin might require eNOS for some of its metabolic effects. J. Cell. Biochem. 113: 3276–3287, 2012. © 2012 Wiley Periodicals, Inc.     

Target network analysis of adiponectin,a multifaceted adipokine

Application of network analysis to dissect the potential molecular mechanisms of biological processes and complicated diseases has been the new trend in biology and medicine in recent years. Among which, the protein–protein interactions (PPI) networks attract interests of most researchers. Adiponectin, a cytokine secreted from adipose tissue, participates in a number of metabolic processes, including glucose regulation and fatty acid metabolism and involves in a series of complicated diseases from head to toe. Hundreds of proteins including many identified and potential drug targets have been reported to be involved in adiponectin related signaling pathways, which comprised a complicated regulation network. Therapeutic target database (TTD) provides extensive information about the known and explored therapeutic protein targets and the signaling pathway information. In this study, adiponectin associated drug targets based PPI was constructed and its topological properties were analyzed, which might provide some insight into the dissection of adiponectin action mechanisms and promote adiponectin signaling based drug target identification and drug discovery. J. Cell. Biochem. 114: 1145–1152, 2013. © 2012 Wiley Periodicals, Inc.     

Promotion of adiponectin multimerization by emodin: A novel AMPK activator with PPARγ-agonist activity

Adiponectin is an important insulin‐sensitizing adipokine with multiple beneficial effects on obesity‐associated medical complications. It is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). Each oligomeric form of adiponectin exerts non‐overlapping biological functions, with the HMW oligomer possessing the most potent insulin‐sensitizing activity. In this study, we reported that emodin, a natural product and active ingredient of various Chinese herbs, activates AMPK in both 3T3‐L1 adipocytes and 293T cells. Activation of AMPK by emodin promotes the assembly of HMW adiponectin and increases the ratio of HMW adiponectin to total adiponectin in 3T1‐L1 adipocytes. Emodin might activate AMPK by an indirect mechanism similar to berberine. We also found that emodin activates PPARγ and promotes differentiation and adiponectin expression during differentiation of 3T3‐L1 preadipocytes. Therefore, emodin is a novel AMPK activator with PPARγ‐agonist activity. Our results demonstrate that the effects of emodin on adiponectin expression and multimerization are the ultimate effects resulting from both AMPK activation and PPARγ activation. The dual‐activity makes emodin or the derivatives potential drug candidates for the treatment of type 2 diabetes and other obesity‐related metabolic diseases. J. Cell. Biochem. 113: 3547–3558, 2012. © 2012 Wiley Periodicals, Inc.