| Summary: | 碩士 === 中山醫學大學 === 營養學研究所 === 100 === Obesity is one of the main public health problems in developed and developing countries. It serves as a significant risk factor for various diseases such as diabetes, cancer, heart disease, and hypertension. A previously study showed that the deep sea water (DSW) inhibits cell number of 3T3-L1 adipocytes and reduced body weight in animals. However, molecular mechanism of DSW on inhibition of adipogenesis is unclear. Therefore, the aim of this study was investigate the effect of DSW on adipogenesis in cell and animal models and its molecular mechanism. There are two topics included in this study, (1) Effect of DSW on inhibition of adipogenesis in 3T3-L1 adipocytes and its molecular mechanism. (2) Antiobesity effect of DSW on obesity rat induced by high-fat diet (HFD) and its molecular mechanism. (1) In cell culture model, the data indicated that the DSW does not inhibit cell numbers of 3T3-L1 pre-adipocytes (MTT assay) and adipocytes (oil o red staining) (p>0.05). But, DSW significantly decreased the intracellular triglyceride and glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 adipocytes. In gene expression, DSW also inhibits expressions of adipocyte differentiation (PPARγ, SREBP-1c, C/EBPα, and C/EBPβ), lipogenesis (ACC, SREBP-1a, and HMG-CoA reductase), and adipocytokine (leptin, IL-6, MCP-1, PAI-1, and CRP), and then up-regulated gene expressions of lipolysis and fatty acid oxidation (ATGL, HSL, CPT-1, and ACO). Our data indicated that DSW inhibits intracellular triglyceride and GPDH activity in 3T3-L1 adipocytes through modulation of gene expressions of adipogenesis and lipolysis. (2) In animal model, the results showed that the body weight [DSW group (1X-5X)], perirenal adipose tissue [DSW group (1X-5X)], liver organ [DSW group (2X-5X)] and, epididymal adipose tissue [DSW group (3X-5X)] in the DSW+HFD groups were significantly decreased as compared to the HFD group (p<0.05). The levels of hepatic triglyceride [DSW group (2X-5X)] and cholesterol [DSW group (3X-5X)] in the DSW+HFD groups were significantly decreased as compared to the HFD group (p<0.05). Serum triglyceride, insulin, and ALT [DSW group (1X-5X)] in the DSW+HFD groups were significantly decreased as compared to the HFD group (p<0.05). Serum glucose [DSW group (2X-5X)], cholesterol [DSW group (1X, 2X, and 5X)], free fatty acid [DSW group (1X, 3X, and 5X)], and AST [DSW group (5X)] in the DSW+HFD groups were significantly decreased as compared to the HFD group (p<0.05). The DSW+HFD groups showed microvesicular fat accumulation in the liver [DSW group (3X-5X)] and adipose tissue [DSW group (1X-5X)]. Moreover, fecal lipid [DSW group (1X-5X)], triglyceride [DSW group (2X-5X)], and cholesterol [DSW group (2X-5X)] output in the DSW+HFD groups were significantly increased as compared to the HFD group (p<0.05). Hepatic malondialdehyde (MDA) in DSW+HFD groups [DSW group (1X and 3X)] were significantly decreased as compared to the HFD group (p<0.05). Hepatic glutathione reductase (GRd) [DSW group (3X-5X)] in DSW+HFD groups were significantly increased as compared to the HFD group(p<0.05). In gene expression, DSW was significantly increased gene expressions of PPARα, AMPK, ACO, and CPT-1 in the hepatic tissue of rats with HFD-induced obesity (p<0.05). Moreover, DSW was significantly increased the gene expressions of lipolysis and fatty acid oxidation (ATGL, HSL, CPT-1, and ACO), and decreased the gene expressions of adipocytokine (TNF-α, PAI-1, and resistin) in adipose tissue of rats with HFD-induced obesity (p<0.05). These results demonstrate that intake of DSW can be beneficial for the suppression of high fat diet-induced dyslipidemia, hepatosteatosis, and oxidative stress in rats.
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