| Summary: | 碩士 === 國立臺灣大學 === 生物化學暨分子生物學研究所 === 95 === Obesity is a risk factor for the development of insulin resistance and type II diabetes. Recent studies suggest that the adipose tissues of genetic or high-fat diet induced obese mice secrete cytokines to recruit macrophage infiltration, which leads to adipose tissue macrophage (ATM) accumulation. The ATM will localize with necrotic adipocytes to phagocyte the debris, and release proinflammmatory cytokines to invoke inflammatory response in adipose tissue leading to insulin resistance.
Fish oil is known to ameliorate insulin resistance and inflammation in rodents, so we speculated that fish oil diet might decrease ATM content to ameliorate insulin resistance. Based on the hypothesis, we studied the effect of high fat diet rich in lard or fish oil on macrophage accumulation in ob/ob mice. In the first experiment, 9-week old ob/ob mice were divided into three groups and were fed with low fat (LF, 4% soybean oil), high fat-lard (Lard, 4% soybean oil + 20% lard) or high fat-fish oil diet ( FO, 4% soybean oil + 20% fish oil) for 10.5 weeks. Final body weights, adipose weights, plasma glucose and cholesterol of FO group were significantly lower than that of Lard group. However, the expression level of ATM surface marker was not different between the FO and Lard groups, which indicated that fish oil did not decrease ATM content, although fish oil can ameliorate insulin resistance in ob/ob mice. We speculated that the characters and physiological significance of ATM in FO group might be different from that of Lard group.
To further investigate the physiological significance of ATM accumulation in FO group, 7-week old ob/ob mice were divided into four groups and were fed with low fat, high fat-lard, high fat-fish oil or rosiglitazone (Rosi) supplemented high fat lard diet (4% soybean oil + 20% lard + 0.0012% rosiglitazone) in the second experiment. After 7 weeks of feeding, final body weights, adipose weights, plasma glucose and cholesterol of FO group were significantly lower than that of Lard group. From the result of immunochemistry and quantitative PCR, we confirmed that the ATM content in FO group was not different from that of Lard group, whereas rosiglitazone decreased the ATM content. Furthermore, TUNEL assay suggested that the content of apoptotic cells in adipose tissues of FO group was higher than that in adipose tissues of Lard group. Analysis of adipose tissue morphology revealed that the average size of adipocytes in FO group was smaller than that of Lard group. From above, we speculate that fish oil will promote apoptosis of large adipocytes thus recruit macrophage infiltration to phagocyte apoptotic cells. Unlike necrotic cells, apoptotic cells may not invoke inflammatory response. The expression level of inflammatory gene such as iNOS was significantly lower in FO group than that of Lard group, and the expression level of anti-inflammatory gene such as IL-10 was higher in FO group than that of Lard group. Taken together, the physiological significance of ATM in FO group is tending to phagocyte apoptotic cells, and the majority of ATM in FO group may have anti-inflammatory or less inflammatory character. In contrast, rosiglitazone decreases inflammatory ATM to ameliorate insulin resistance. The mechanism of insulin sensitivity improvement by rosiglitazone and fish oil is not the same.
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