In a recent article published in Nature,Patel et al.identified adipose triglyceride lipase(ATGL,also known as patatin-like phospholipase domain containing 2)as the first biosynthetic enzyme of fatty acid esters of hyd...In a recent article published in Nature,Patel et al.identified adipose triglyceride lipase(ATGL,also known as patatin-like phospholipase domain containing 2)as the first biosynthetic enzyme of fatty acid esters of hydroxy fatty acids(FAHFAs),further expanding the knowledge on bioactive lipid research and being a potential paradigm shift for ATGL studies.FAHFAs are a class of diverse lipids that contain two fatty acids linked by a hydroxyl ester group[1].Although FAHFAs were initially identified in insects and plants,the intense interest was not ignited until 2014 when a landmark study by Yore et al.展开更多
Brown adipose tissue (BAT) plays an essential role in non-shivering thermogenesis. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) is identified as a lipid transporter that reciprocally transfers ph...Brown adipose tissue (BAT) plays an essential role in non-shivering thermogenesis. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) is identified as a lipid transporter that reciprocally transfers phospholipids between intracellular membrane structures. However, the physiological significance of PITPNC1 and its regulatory mechanism remain unclear. Here, we demonstrate that PITPNC1 is a key player in thermogenesis of BAT. While Pitpnc1^(−/−) mice do not differ with wildtype mice in body weight and insulin sensitivity on either chow or high-fat diet, they develop hypothermia when subjected to acute cold exposure at 4℃. The Pitpnc1^(−/−) brown adipocytes exhibit defective β-oxidation and abnormal thermogenesis-related metabolism pathways in mitochondria. The deficiency of lipid mobilization in Pitpnc1^(−/−) brown adipocytes might be the result of excessive accumulation of phosphatidylcholine and a reduction of phosphatidic acid. Our findings have uncovered significant roles of PITPNC1 in mitochondrial phospholipid homeostasis and BAT thermogenesis.展开更多
Brown adipose tissue(BAT)plays a key role in thermogenesis during acute cold exposure.However,it remains unclear how BAT is prepared to rapidly turn on thermogenic genes.Here,we show that damage-specific DNA binding p...Brown adipose tissue(BAT)plays a key role in thermogenesis during acute cold exposure.However,it remains unclear how BAT is prepared to rapidly turn on thermogenic genes.Here,we show that damage-specific DNA binding protein 1(DDB1)mediates the rapid transcription of thermogenic genes upon acute cold exposure.Adipose-or BAT-specific Ddb1 knockout mice show severely whitened BAT and significantly decreased expression of thermogenic genes.These mice develop hypothermia when subjected to acute cold exposure at 4℃ and partial lipodystrophy on a high-fat diet due to deficiency in fatty acid oxidation.Mechanistically,DDB1 binds the promoters of Ucp1 and Ppargc1a and recruits positive transcriptional elongation factor b(P-TEFb)to release promoter-proximally paused RNA polymerase II(Pol II),thereby enabling rapid and synchronized transcription of thermogenic genes upon acute cold exposure.Our findings have thus provided a regulatory mechanism of how BAT is prepared to respond to acute cold challenge.展开更多
基金T.J.Z.and J.W.are supported by the National Natural Science Foundation of China(32125022 and 92157301 to T.J.Z.,32100539 to J.W.)G.L.is supported by grants from the NIH(P01HL20948-45 and P01HL60487-01).
文摘In a recent article published in Nature,Patel et al.identified adipose triglyceride lipase(ATGL,also known as patatin-like phospholipase domain containing 2)as the first biosynthetic enzyme of fatty acid esters of hydroxy fatty acids(FAHFAs),further expanding the knowledge on bioactive lipid research and being a potential paradigm shift for ATGL studies.FAHFAs are a class of diverse lipids that contain two fatty acids linked by a hydroxyl ester group[1].Although FAHFAs were initially identified in insects and plants,the intense interest was not ignited until 2014 when a landmark study by Yore et al.
基金the National Key R&D Program of China(2018YFA0506900)the National Key R&D Program of China(2018YFA0800301)+3 种基金the National Natural Science Foundation of China(91857103)Shanghai Basic Research Field Project“Science and Technology Innovation Action Plan”(21JC1400400)the Lingang Laboratory(LG-QS-202204-06)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)。
文摘Brown adipose tissue (BAT) plays an essential role in non-shivering thermogenesis. The phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) is identified as a lipid transporter that reciprocally transfers phospholipids between intracellular membrane structures. However, the physiological significance of PITPNC1 and its regulatory mechanism remain unclear. Here, we demonstrate that PITPNC1 is a key player in thermogenesis of BAT. While Pitpnc1^(−/−) mice do not differ with wildtype mice in body weight and insulin sensitivity on either chow or high-fat diet, they develop hypothermia when subjected to acute cold exposure at 4℃. The Pitpnc1^(−/−) brown adipocytes exhibit defective β-oxidation and abnormal thermogenesis-related metabolism pathways in mitochondria. The deficiency of lipid mobilization in Pitpnc1^(−/−) brown adipocytes might be the result of excessive accumulation of phosphatidylcholine and a reduction of phosphatidic acid. Our findings have uncovered significant roles of PITPNC1 in mitochondrial phospholipid homeostasis and BAT thermogenesis.
基金This work was supported by the National Key R&D Program of China(2020YFA0803601)the National Natural Science Foundation of China(32125022 and 32101046)the China Postdoctoral Science Foundation(2019M661348 and 2020T130115).
文摘Brown adipose tissue(BAT)plays a key role in thermogenesis during acute cold exposure.However,it remains unclear how BAT is prepared to rapidly turn on thermogenic genes.Here,we show that damage-specific DNA binding protein 1(DDB1)mediates the rapid transcription of thermogenic genes upon acute cold exposure.Adipose-or BAT-specific Ddb1 knockout mice show severely whitened BAT and significantly decreased expression of thermogenic genes.These mice develop hypothermia when subjected to acute cold exposure at 4℃ and partial lipodystrophy on a high-fat diet due to deficiency in fatty acid oxidation.Mechanistically,DDB1 binds the promoters of Ucp1 and Ppargc1a and recruits positive transcriptional elongation factor b(P-TEFb)to release promoter-proximally paused RNA polymerase II(Pol II),thereby enabling rapid and synchronized transcription of thermogenic genes upon acute cold exposure.Our findings have thus provided a regulatory mechanism of how BAT is prepared to respond to acute cold challenge.
