Brown adipose tissue(BAT)is an energy-expending organ that produces heat.Expansion or activation of BAT prevents obesity and diabetes.Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1(UC...Brown adipose tissue(BAT)is an energy-expending organ that produces heat.Expansion or activation of BAT prevents obesity and diabetes.Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1(UCP1)activation triggered via a b-adrenergic pathway.Here,we report that the cold-sensing transient receptor potential melastatin 8(TRPM8)is functionally present in mouse BAT.Challenging brown adipocytes with menthol,a TRPM8 agonist,up-regulates UCP1 expression and requires protein kinase A activation.Upon mimicking long-term cold exposure with chronic dietary menthol application,menthol significantly increased the core temperatures and locomotor activity in wild-type mice;these effects were absent in both TRPM82/2 and UCP12/2 mice.Dietary obesity and glucose abnormalities were also prevented by menthol treatment.Our results reveal a previously unrecognized role for TRPM8,suggesting that stimulation of this channel mediates BAT thermogenesis,which could constitute a promising way to treat obesity.展开更多
Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches,either pancreatic lipase in...Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches,either pancreatic lipase inhibitors or appetite suppressors, are generally of limited effectiveness. Brown adipose tissue(BAT) and beige cells dissipate fatty acids as heat to maintain body temperature, termed non-shivering thermogenesis; the activity and mass of BAT and beige cells are negatively correlated with overweight and obesity. The existence of BAT and beige cells in human adults provides an effective weight reduction therapy, a process likely to be amenable to pharmacological intervention. Herein, we combed through the physiology of thermogenesis and the role of BAT and beige cells in combating with obesity. We summarized the thermogenic regulators identified in the past decades, targeting G proteincoupled receptors, transient receptor potential channels, nuclear receptors and miscellaneous pathways.Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of thermogenesis in energy homeostasis to the representative thermogenic regulators for treating obesity. Thermogenic regulatorsmight have a large potential for further investigations to be developed as lead compounds in fighting obesity.展开更多
基金supported by grants from the National Basic Research Program of China (2012CB517805 and 2012CB517806)the National Natural Science Foundation of China (30890042)supported by the Program for Changjiang Scholars from the Ministry of Education in China.
文摘Brown adipose tissue(BAT)is an energy-expending organ that produces heat.Expansion or activation of BAT prevents obesity and diabetes.Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1(UCP1)activation triggered via a b-adrenergic pathway.Here,we report that the cold-sensing transient receptor potential melastatin 8(TRPM8)is functionally present in mouse BAT.Challenging brown adipocytes with menthol,a TRPM8 agonist,up-regulates UCP1 expression and requires protein kinase A activation.Upon mimicking long-term cold exposure with chronic dietary menthol application,menthol significantly increased the core temperatures and locomotor activity in wild-type mice;these effects were absent in both TRPM82/2 and UCP12/2 mice.Dietary obesity and glucose abnormalities were also prevented by menthol treatment.Our results reveal a previously unrecognized role for TRPM8,suggesting that stimulation of this channel mediates BAT thermogenesis,which could constitute a promising way to treat obesity.
基金Financial support by Science and Technology Development Fund,Macao SAR,China(FDCT 102/2017/A)the Research Fund of University of Macao,China(MYRG2017-00109-ICMS)
文摘Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches,either pancreatic lipase inhibitors or appetite suppressors, are generally of limited effectiveness. Brown adipose tissue(BAT) and beige cells dissipate fatty acids as heat to maintain body temperature, termed non-shivering thermogenesis; the activity and mass of BAT and beige cells are negatively correlated with overweight and obesity. The existence of BAT and beige cells in human adults provides an effective weight reduction therapy, a process likely to be amenable to pharmacological intervention. Herein, we combed through the physiology of thermogenesis and the role of BAT and beige cells in combating with obesity. We summarized the thermogenic regulators identified in the past decades, targeting G proteincoupled receptors, transient receptor potential channels, nuclear receptors and miscellaneous pathways.Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of thermogenesis in energy homeostasis to the representative thermogenic regulators for treating obesity. Thermogenic regulatorsmight have a large potential for further investigations to be developed as lead compounds in fighting obesity.
