| Summary: | 博士 === 國立嘉義大學 === 食品科學系研究所 === 103 === Obesity is defined as an excess body fat composition. The adipose tissue mass is regulated by the adipocyte number resulted from pre-adipocyte differentiation, hyperplasia, and the enlargement of mature cells due to the accumulation of intracellular triglyceride, hypertrophy. Obesity increases the incidence and risk of a number of chronic diseases, including insulin resistance, type 2 diabetics, atherosclerosis, ischemic heart disease, fatty liver, dementia and cancer, and has become a major global health concern. Adipose tissue is an energy depot as well an endocrine organ releasing numbers of adipokines. Accumulating evidence indicate that the interaction of adipocytes and residential macrophages triggers chronic systemic inflammation, referring to metaflammation, and contributes to the pathogenesis of complications associated with obesity. Thus, down regulating hyperplasia and hypertrophy, and preventing metaflammation in adipose tissue are therapeutic strategies for obesity. The goal of the current study was to determine the functionality and molecular mechanism of theaflavin-3,3′-digallate (TF3), a major polyphenolic compound in black tea, in obesity prevention. The objectives of the study were to investigate (1) effect of TF3 on pre-adipocyte differentiation; (2) effect of TF3 on lipid metabolism of mature adipocytes; (3) efficacy and mechanism of TF3 in preventing metaflammation. Results showed that TF3 attenuated pre-adipocyte differentiation likely through mediating antioxidant enzyme gene expression, and down-regulating ROS production in mitochondria. TF3 inhibited lipogenesis and increased uncoupling proteins expression in mature adipocytes. The study in the cell co-culture system comprising adipocytes and macrophages indicated that adipocytes play an important role in the initiation of metaflammation, triggering inflammatory response of macrophages. TF3 attenuates the induction of inflammatory mediators and promoted the shift of inflammatory M1-like macrophages induced by adipocytes toward a less inflammatory M2-like phenotype. Furthermore, the modulating activity of TF3 in adipocytes is through AMPK dependent pathway. In conclusion, TF3 may elicit beneficial effect in obesity by down regulation of hyperplasia and hypertrophy, and prevention of metaflammation, which can be used for the development of functional food products.
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