Ginger extract controls mTOR-SREBP1-ER stress-mitochondria dysfunction through AMPK activation in obesity model

Abstract Ginger is a tropical plant widely grown in tropical and subtropical countries and used as a spice and traditional medicine in Asia, but its effectiveness against obesity and associated mechanisms have not been thoroughly studied. We investigated steamed ginger extract’s (SGE) potential anti-obesity effects in high-fat diet (HFD) mouse model. It was observed that HFD-fed mice showed low body weight gain and a significant decrease in epididymal fat and inguinal fat mass. Also, SGE inhibited serum hepatic enzymes and controlled lipid profile and adipokines in HFD-fed mice. In the white adipose tissues (WAT), morphological alteration and fatty acid synthesis genes such as SREBP1 and FAS were decreased by SGE supplementation. In the SGE-supplemented groups, whitening of brown adipose tissue (BAT) characterized by increased lipid deposition and mitochondrial dysfunction was inhibited, and there was a recovery of the reduced mitochondrial DNA and complex I and III enzyme activities and thermogenesis genes, including UCP1. In the liver and adipocyte tissues, hyper-nutrient condition-based mTOR-SREBP1-ER stress-induced ROS amplification leading to mitochondrial dysfunction. Here, cellular-based pathological signaling for hepatic and adipocytic dysmetabolism is controlled by the SGE in which AMPK-SIRT1 is involved. To summarize, SGE significantly reduced liver steatosis and adipocyte metabolic deterioration with AMPK-SIRT-1 activation and ROS-linked interstitial disorders related to the endoplasmic reticulum (ER) and mitochondrial redox.