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Title: Pterostilbene, a natural phytochemical, ameliorates fatty liver disease in in vitro and in vivo models
Authors: Ng, Yam Fung
Degree: Ph.D.
Issue Date: 2019
Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease resulting from non-alcoholic causes of excessive deposition of fat in hepatocytes. It encompasses a spectrum of conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which can further progress to fibrosis, cirrhosis and hepatic carcinoma. Over the past few decades, the prevalence of NAFLD increases worldwide due to the spread of Western lifestyle in the developing countries. In recent years, there is increasing incidence of NAFLD in younger generation. The rising incidence of NAFLD has become a serious global public health issue. Currently, there is no standard therapeutic medical treatment for NAFLD. Lifestyle modification is the mainstay of treatment, but it may be difficult for patients to maintain these long-term lifestyle changes. Medication to improve the efficacy of lifestyle measures is warranted. Pterostilbene (3,5-dimethoxy-4-hydroxy-trans-stilbene), a methylated analogue of resveratrol, has been reported to possess various biological activities, including antioxidative, anti-inflammatory, anti-diabetic, and anti-cancer effects. The properties of pterostilbene may be able to target the pathogenic processes in the progression of NAFLD. The objectives of the present study include (1) to investigate the protective effect of pterostilbene against oxidative stress as well as its lipid reduction effect and the possible molecular mechanisms using steatotic hepatic cell model in vitro; (2) to evaluate the potential therapeutic effects of pterostilbene against NAFLD using high-fat diet-induced hepatic steatosis animal model in vivo; and (3) to investigate the possible mechanistic pathways of pterostilbene in treating NAFLD using molecular, lipidomic and genomic approaches. Results of in vitro study demonstrated that pterostilbene could protect liver cells against oxidative stress via downregulation of MAPKs and upregulation of HO-1. Moreover, results of in vitro study showed that pterostilbene could reduce intracellular lipid accumulation in steatotic liver cells by inhibiting fatty acid synthesis as well as cholesterol synthesis and promoting fatty acid β-oxidation and lipophagy. Results of in vivo study demonstrated that treatment with pterostilbene could help reduce liver lipid content and attenuate insulin resistance. The underlying mechanisms may include protection against high-fat diet-induced oxidative stress, inhibition of fatty acid synthesis as well as cholesterol synthesis, promoting fatty acid β-oxidation and lipophagy, restoration of the high-fat diet-induced changes in the serum metabolites of lysophospholipids as well as the high-fat diet-induced alteration of gut microbiota structure. In conclusion, the present studies showed that pterostilbene could help ameliorate NAFLD in vitro and in vivo by multiple mechanisms. Further studies are required to determine the potential of using pterostilbene as therapeutic agents for NAFLD in clinical settings.
Subjects: Hong Kong Polytechnic University -- Dissertations
Fatty liver
Liver -- Diseases
Antioxidants -- Therapeutic use
Pages: xix, 193 pages : color illustrations
Appears in Collections:Thesis

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