Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed tha...Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4- deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 （UCP2） and p-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue （WAT）, suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue （BAT）, suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.展开更多
G-protein coupled receptors(GPCRs)compromise the largest membrane protein superfamily which play vital roles in physiological and pathophysiological processes including energy homeostasis.Moreover,they also represent ...G-protein coupled receptors(GPCRs)compromise the largest membrane protein superfamily which play vital roles in physiological and pathophysiological processes including energy homeostasis.Moreover,they also represent the up-to-date most successful drug target.The gut hormone GPCRs,such as glucagon receptor and GLP-1 receptor,have been intensively studied for their roles in metabolism and respective drugs have developed for the treatment of metabolic diseases such as type 2 diabetes(T2D).Along with the advances of biomedical research,more GPCRs have been found to play important roles in the regulation of energy homeostasis from nutrient sensing,appetite control to glucose and fatty acid metabolism with various mechanisms.The investigation of their biological functions will not only improve our understanding of how our body keeps the balance of energy intake and expenditure,but also highlight the possible drug targets for the treatment of metabolic diseases.The present review summarizes GPCRs involved in the energy control with special emphasis on their pathophysiological roles in metabolic diseases and hopefully triggers more intensive and systematic investigations in the field so that a comprehensive network control of energy homeostasis will be revealed,and better drugs will be developed in the foreseeable future.展开更多
Bile acids(BAs)are originally known as detergents essential for the digestion and absorption of lipids.In recent years,extensive research has unveiled new functions of BAs as gut hormones that modulate physiological a...Bile acids(BAs)are originally known as detergents essential for the digestion and absorption of lipids.In recent years,extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes,including glucose and lipid metabolism,energy expenditure,inflammation,tumorigenesis,cardiovascular disease,and even the central nervous system in addition to cholesterol homeostasis,enterohepatic protection and liver regeneration.BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs.The signaling actions of BAs can also be mediated through specific nuclear receptors and membranebound G protein-coupled receptors.Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling.In this mini-review,we summarize recent advances in bile-ology,focusing on its translational studies.展开更多
文摘Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4- deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 （UCP2） and p-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue （WAT）, suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue （BAT）, suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.
文摘G-protein coupled receptors(GPCRs)compromise the largest membrane protein superfamily which play vital roles in physiological and pathophysiological processes including energy homeostasis.Moreover,they also represent the up-to-date most successful drug target.The gut hormone GPCRs,such as glucagon receptor and GLP-1 receptor,have been intensively studied for their roles in metabolism and respective drugs have developed for the treatment of metabolic diseases such as type 2 diabetes(T2D).Along with the advances of biomedical research,more GPCRs have been found to play important roles in the regulation of energy homeostasis from nutrient sensing,appetite control to glucose and fatty acid metabolism with various mechanisms.The investigation of their biological functions will not only improve our understanding of how our body keeps the balance of energy intake and expenditure,but also highlight the possible drug targets for the treatment of metabolic diseases.The present review summarizes GPCRs involved in the energy control with special emphasis on their pathophysiological roles in metabolic diseases and hopefully triggers more intensive and systematic investigations in the field so that a comprehensive network control of energy homeostasis will be revealed,and better drugs will be developed in the foreseeable future.
基金Project supported by the National Cancer Institute(No.2R01CA139158)John Hench Foundation to Wen-dong HUANGthe National Natural Science Foundation of China(Nos.81471084 and 81773793)to Li-hua JIN
文摘Bile acids(BAs)are originally known as detergents essential for the digestion and absorption of lipids.In recent years,extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes,including glucose and lipid metabolism,energy expenditure,inflammation,tumorigenesis,cardiovascular disease,and even the central nervous system in addition to cholesterol homeostasis,enterohepatic protection and liver regeneration.BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs.The signaling actions of BAs can also be mediated through specific nuclear receptors and membranebound G protein-coupled receptors.Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling.In this mini-review,we summarize recent advances in bile-ology,focusing on its translational studies.
