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International Textbook of Obesity - part 6

fects mô nhiều, và bằng chứng sau đây đã được thu được kết quả trong hành động glucocorticoid suy yếu trong não, gan và chất béo có thể ngoại vi. Trong PEPCK, gan, các enzyme giới hạn tốc độ | 256 INTERNATIONAL TEXTBOOK OF OBESITY fects multiple tissues and the following evidence has been obtained that it results in attenuated glucocorticoid action in liver brain and possibly peripheral fat. In the liver PEPCK the rate-limiting enzyme in gluconeogenesis which is downregulated byinsulin and upregulated byglucocorticoids shows an impaired induction in response to fasting in 11 -HSD animals Figure 18.6c . This is consistent with the interpretation of pharmacological experiments see above that 11 -HSD1 maintains in-trahepatic glucocorticoid receptor activation. When 11 -HSD1 animals are fed a high-fat cafeteria diet theygain less weight and have lower plasma glucose levels than wild-type controls. The latter is consistent with effects on the hepatic gluconeogenic response to insulin but the former maybe explained byadditional central effects of 11 -HSD1 on regulation of energy xppedditure and or an influence of 11 -HSD1 on adipocyte metabolism. Appetite and energy e X pen di tu re have eet to be examined. Interestingly however body fat distribution in animals on normal chow is not obvi-ouslydifferent from wild type. 11 -HSD1 mice are also hyper-corticos-teronaemic consistent with a defect in negative feedback regulation of the hypothalamic-pituitaryadrenal axis. 5a-Reductase Knockout Mice Mice with transgenic deletion of both isozymes of 5a-reductase have been reported 86 153 . The 5a-reductase type 2 knockout surprisingly has no abnormality of prostate or genital development but in rodents 5a-reductase type 1 is co-expressed and could compensate. The 5a-reductase type 1 knockout also has no major phenotypic abnormality except an increased risk of in utero death attributed to diversion of androgens to oestrogens instead of 5a-dihydrotestosterone 86 . However glucocorticoid metabolism and action has not been reported in these animals. Pharmacological Manipulation Liquorice and its Derivatives Extracts from the liquorice root have been used as confectioneryand