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

Abstract

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.

The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA)

“…Furthermore, adiponectin gene therapy has been demonstrated to restore SERCA gene expression in skeletal muscle of rats fed a high-fat diet, with further benefits resulting from combination therapy involving adiponectin and 9-weeks of aerobic swim training (Safwat et al 2013). This result has also been confirmed in H9C2 cells, where cardiomyocytes cultured in an adiponectin-enriched medium for 1 h demonstrated a 30% increase in SERCA2a mRNA compared with cells cultured in an adiponectin-depleted medium (Boddu et al 2014). Although the precise mechanism by which adiponectin enhances SERCA2a activity has yet to be fully elucidated, it may occur through an increased phosphorylation of the regulatory molecule PLN.…”

Adipokines and Inflammation: Focus on Cardiovascular Diseases

“…Adiponectin is expressed and secreted by human and murine cardiomyocytes, where it enhances glucose and fatty acid uptake, suggesting a role of adiponectin in regulating cardiac metabolism and function [ 222 ]. In hearts from adiponectin-knockout mice, there is an increased expression of endoplasmic reticulum stress and inflammatory genes such as TNFα and MCP-1, an effect that is reverted by adiponectin treatment of H9C2 cardiomyocytes with induced endoplasmic reticulum stress and in HUVECs in sepsis [ 223 , 224 ]. In the same line, several studies have shown that adiponectin also protects the heart from I/R injury through the inhibition of endoplasmic reticulum stress [ 225 , 226 , 227 ] and that TNFα antagonism improves myocardial I/R injury by upregulating adiponectin expression in mice [ 228 ].…”

Altered sarco(endo)plasmic reticulum calcium adenosine triphosphatase 2a content: Targets for heart failure therapy

“…90 Adiponectin shows efficient cardioprotective effect by facilitating recovery of SERCA2a activity through lowering inflammation and ameliorating ER stress in animal models with heart failure. 90,91 The regulation mechanism of adiponectinon is further investigated, during which increased phosphorylation level of PLN is always viewed, 90 although the precise role remains mysterious. Furthermore, adiponectin can also affect on the signalling of adenosine monophosphate-activated protein kinase (AMPK), 92 which plays a pivotal role in energy homeostasis and induces the alteration of SERCA1a protein and SERCA2a mRNA.…”