Intermittent injections of osteocalcin reverse autophagic dysfunction and endoplasmic reticulum stress resulting from diet-induced obesity in the vascular tissue via the NFκB-p65-dependent mechanism

• DOI: 10.4161/cc.24929
• Publication Date: 2013-06-17T14:57:07Z
• Authors: Bo Zhou; Huixia Li; Jiali Liu; Lin Xu; Weijin Zang; Shufang Wu; Hongzhi Sun
• Keywords: Tunicamycin; Endothelial Dysfunction

The osteoblast-specific secreted molecule osteocalcin behaves as a hormone-regulating glucose and lipid metabolism, but the role of in cardiovascular disease (CVD) is not fully understood. In present study, we investigated effect on autophagy endoplasmic reticulum (ER) stress secondary to diet-induced obesity vascular tissue mice cell models clarified intracellular events responsible for osteocalcin-mediated effects. evidences showed that intermittent injections fed high-fat diet were associated with reduced body weight gain, decreased blood improved insulin sensitivity compared receiving vehicle. Simultaneously, administration only attenuated ER also rescued impaired signaling tissues diet. Consistent these results vivo, addition reversed restored defective endothelial cells (VECs) smooth muscle (VSMCs) presence tunicamycin or knockout XBP-1 (a transcription factor which mediates response) Atg7−/− cells. protective effects nullified by suppression Akt, mammalian target rapamycin (mTOR) nuclear kappa B (NFκB), suggesting inhibits autophagy, improves under resistance NFκB-dependent manner, may be promising therapeutic strategies dysfunction obesity.