부산대학교 도서관

With the rapid increase in the prevalence of metabolic syndrome, its mechanism and increased risk of hypertension, atherosclerosis, stroke and type 2 diabetes would be novel investigated point within future decades. So far, metabolic disorder-associated underlying causes include overweight, insulin resistance, physical inactivity, genetic factors, obesity, and increasing age. On a global scale, metabolic disorder-related obesity and nonalcoholic fatty liver disease (NAFLD) have become the most common causes of chronic disease regard to the increased morbidity. However, the pathological mechanisms involving NAFLD and obesity have not been extremely clarified. The causes were originally ascribed to lipid metabolism disorders coupled with oxidative stress. Currently, other factors and pathogenic mechanisms are likely responsible for tissue injury and the promotion of disease progression.As known, obesity epidemic is also associated with a raised risk of NAFLD, not only has been linked with simple steatosis, also with some advanced diseases, such as NASH (nonalcoholic steatohepatitis), cirrhosis and hepatocellular carcinoma. Besides, obesity leads to the development of metabolic syndrome and comorbidities. As a consequence, obesity increases liver-specific mortality in NAFLD patient. Given the lack of approved pharmacological interventions for NAFLD, targeting obesity is a rational option for its management. Ginger (Zingiber officinale) is a tropical plant that is widely cultivated in tropical and subtropical countries and is used as a spice and traditional medicine in Asia. It is used to treat hyperlipidemia and fatty liver disease. However, its effectiveness against obesity and the mechanisms underlying it are not well understood. I examined the potential anti-obesity benefits of steamed ginger extract (SGE) in HFD (high-fat diet)-fed animal model, whitening of brown adipose tissue (BAT), and recovery of mitochondrial DNA and complex I and III enzyme activity, as well as thermogenesis genes, including UCP1. SGE substantially inhibited hepatic steatosis and adipocyte metabolic degradation associated with AMPK-SIRT-1 activation, as well as ROS-linked interstitial diseases involving the endoplasmic reticulum (ER) and mitochondrial redox. Additionally, I also investigated obesity improvement through treatment of a rare sugar, D-allulose, which is a naturally occurring carbohydrate in vegetables and fruits, a C-3 epimer of D-fructose. Previous studies have indicated that when D-allulose is administered by oral gavage, only 70% of D-allulose is absorbed and is excreted via urine, but the residual part is not utilized or fermented in the large intestine, suggesting that D-allulose is unlikely to be stored in the body. This work indicates that D-allulose may repress adipocyte differentiation by modulating the PPARγ and C/EBPα signaling pathways and adipogenesis-related genes via the coordinated action of the AMPK/SIRT1 axis. Likewise, D-allulose administration induced PGC-1α expression, therefore initiating mitochondrial genesis in adipose tissue via increasing AMPK phosphorylation and SIRT1 deacetylation activity. The anti-obesity effect of D-allulose is based on a marked alleviation in adipogenesis and synergistic regulation of AMPK/SIRT1/PGC-1α deacetylation in the adipose tissue of HFD-fed rats.Cellular senescence has been shown to be strongly related with NAFLD. Senescent cells have been found in the hepatocytes of humans and animals with NAFLD, and an increasing percentage of senescent hepatocytes appears to be independently associated with disease progression. Additionally, hepatocyte senescence has been shown to contribute to the pathogenesis of NAFLD by increasing hepatic fat accumulation and steatosis. These findings indicate that hepatocyte senescence plays a critical role in the pathophysiology of NAFLD. Eucommia ulmoides leaf extract (EUL), termed Du-Zhong as well, are used to be utilized as anti-hypertension, anti-cardiovascular disease, anti-hypercholesterolemia, and anti-fatty liver disease in China, Korea and Japan. In a rodent model of aging-related NAFLD, my research demonstrated the protective impact of EUL and the underlying mechanism. EUL supplementation (200 mg/kg) inhibited both hepatocyte senescence and fat accumulation via the mTORC1-ER and AMPK-SIRT1 signaling pathways, as well as correcting altered autophagic flux. I found that EUL appears to safeguard against deterioration of autophagy flux by improving the ER stress response and activating SIRT1, resulting in an increase in deacetylation, which facilitates autophagosome expansion and elongation. Additionally, EUL supplementation reduced hepatic steatosis by regulating ROS accumulation in the liver associated with dysmetabolism. The findings suggest that EUL may pave the way for the development of new therapeutic and preventative medicines for age-related NAFLD.