During the past 20 years, there has been a significant increase in obesity around the world. This growing epidemic is due in part to poor eating behavior, which is controlled by multiple factors including food palatability and nutritional needs. External chemosensory sugar receptors primarily detect palatable food, but animals without sugar receptors can still develop a preference for sugars based on their nutritional value. These studies suggest the existence of a taste-independent sugar receptor, the identity of which remains unknown. In the seminar, I will describe a mutation in a sodium/solute cotransporter-like protein in Drosophila melanogaster, designated dSLC5A11, that is completely insensitive to the nutritional value of sugar, but responds only to the concentration . dSLC5A11 is structurally similar to mammalian sodium/glucose cotransporters that transport sugar in bulk across the intestinal and renal lumen. However, dSLC5A11 has a prominent expression in 10-13 pairs of R4 neurons of the ellipsoid body in the brain. Its activity appears to differ from that of its mammalian counterparts, in that it functions in R4 neurons for selecting appropriate foods without the influence of taste. Given their restricted expression pattern and the specificity of their function, we propose that dSLC5A11 and EB R4 neurons carry out a critical signaling function in sensing glycemic levels of the internal milieu, which, in turn, may dictate the desire for nutritive sugar. Our finding may reveal information that can serve as a valuable framework for studying the mechanism by which nutritional need influences eating behavior in normal and obese individuals.
二零一二年八月4日，U.S.A.London高校法学中央Skirball分子生物医研所助理教授GregSuh 大学生应邀做客研讨所并设置学术讲座。讲座的难题为：Interoceptive Sugar Sensing in Drosophil 罗敏敏学士主持讲座。
Energy metabolism in animals is temporally tuned by endogenous circadian oscillators and feeding-fasting cycles. The relevance of these metabolic cycles in protecting against nutritional challenges that lead to obesity and diabetes has not been conclusively tested. While diet-induced obesity has been attributed to increased caloric intake from fat, animals fed high fat diet ad libitum exhibit a disrupted daily feeding rhythm. These animals eat frequently throughout the day and night losing the feeding cycle preserved in normal chow controls. To test whether obesity and metabolic diseases result from high fat diet or disruption of metabolic cycles, we subjected mice to either ad libitum or time restricted access to food for 8-12 h/day for more than 100 days. Mice with time restricted access to food consume the equivalent amount of calories from high fat diet as those with ad lib access, yet are protected against obesity, hyperinsulinemia, hyperleptinmenia, hepatic steatosis, inflammation, and have improved motor coordination. Time restricted feeding regimen improved CREB, mTOR and AMP-activated Protein Kinase pathway function, oscillations of the hepatic circadian oscillators, and their target genes’ expression. These changes in catabolic and anabolic pathways led to reduced gluconeogenesis and lipogenesis, improvements in glycolysis, beta-oxidation, bile acid production, and energy expenditure. Thus, tRF regimen is a potential non-pharmacological strategy for combating obesity and its associated metabolic diseases.
2015年十一月1日，美利坚联邦合众国Saul克生物学讨论所（Salk Institute for Biological Studies）的分子生物学教师 Satchin Panda大学生应邀访谈商量所并开办学术讲座。讲座的难题为：Rhythmic feeding and fasting prevents metabolic diseases in mice。张二荃硕士主持讲座。