Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL ...Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL in the regulating absorption and transport of fatty acid,as well as the connection between ACSL and some metabolic diseases.展开更多
Fatty acid synthase （FAS） attracts more and more attention recently as a potential target for metabolic syndrome,such as cancer, obesity, diabetes and cerebrovascular disease. FAS inhibitors are widely existed in pl...Fatty acid synthase （FAS） attracts more and more attention recently as a potential target for metabolic syndrome,such as cancer, obesity, diabetes and cerebrovascular disease. FAS inhibitors are widely existed in plants, consisting of diversiform compounds. These inhibitors exist not only in herbs also in many plant foods, such as teas, allium vegetables and some fruits. These effective components include gallated catechins, theaflavins,flavonoids, condensed and hydrolysable tannins, thioethers,pentacyclic triterpenes, stilbene derivatives, etc, and they target at the different domains of FAS, showing different inhibitory mechanisms. Interestingly, these FAS inhibitor-contained herbs and plant foods and their effective components are commonly related to the prevention of metabolic syndromes including fatreducing and depression of cancer. From biochemical angle,FAS can control the balance between energy provision and fat production. Some studies have shown that the effects of those effective components in plants on metabolic syndromes are mediated by inhibiting FAS. This suggests that FAS plays a critical role in the regulation of energy metabolism, and the FAS inhibitors from plants have significant potential application value in the treatment and prevention of metabolic syndromes.展开更多
Acyl-coenzyme A thioesters(acyl-CoAs)denote a key class of intermediary metabolites that lies at the hub of major metabolic pathways.The great diversity in polarity between short-and long-chain acylCoAs makes it techn...Acyl-coenzyme A thioesters(acyl-CoAs)denote a key class of intermediary metabolites that lies at the hub of major metabolic pathways.The great diversity in polarity between short-and long-chain acylCoAs makes it technically challenging to cover an inclusive range of acyl-CoAs within a single method.Levels of acyl-carnitines,which function to convey fatty acyls into mitochondria matrix forβ-oxidation,indicate the efficiency of mitochondrial import and utilization of corresponding acyl-CoAs.Herein,we report a robust,integrated platform to allow simultaneous quantitation of endogenous acyl-CoAs and acyl-carnitines.Using this method,we monitored changes in intermediary lipid profiles across Drosophila development under control(ND)and high-fat diet(HFD).We observed specific accumulations of medium-chain(C8-C12)and long-chain(≥C16)acyl-carnitines distinct to L3 larval and pupal stages,respectively.These observations suggested development-specific,chain length-dependent disparity in metabolic fates of acyl-CoAs across Drosophila development,which was validated by deploying the same platform to monitor isotope incorporation introduced from labelled 12:0 and 16:0 fatty acids into extra-and intra-mitochondrial acyl-CoA pools.We found that pupal mitochondria preferentially import and oxidise C12:0-CoAs(accumulated as C12:0-carnitines in L3 stage)over C16:0-CoAs.Preferential oxidation of medium-chain acyl-CoAs limits mitochondrial utilization of long-chain acyl-CoAs(C16-C18),leading to pupal-specific accumulation of long-chain acyl-carnitines mediated by enhanced CPT1-6 A activity.HFD skewed C16:0-CoAs towards catabolism over anabolism in pupa,thereby adversely affecting overall development.Our developed platform emphasizes the importance of integrating biological knowledge in the design of pathway-oriented platforms to derive maximal physiological insights from analysis of complex biological systems.展开更多
Hummingbird migration is a remarkable feat, given the small body sizes of migratory species, their high metabolic rates during flight and the long distances traveled using fat to fuel the effort. Equally remarkable is...Hummingbird migration is a remarkable feat, given the small body sizes of migratory species, their high metabolic rates during flight and the long distances traveled using fat to fuel the effort. Equally remarkable is the ability of premigratory hummingbirds in the wild to accumulate fat, synthesized from sugar, at rates as high as 10% of body mass per day. This paper summarizes, using Rumsfeldian terminology, ＂known knowns＂ concerning the energetics of hummingbird migration and premi- gratory fattening. Energy metabolism during hover-feeding on floral nectar is fueled directly by dietary sugar through the path- way recently named the ＂sugar oxidation cascade＂. However, flight without feeding for more than a few minutes requires shifting to fat as a fuel. It is proposed that behavior and metabolic fuel choice are coadapted to maximize the rate of fat deposition during premigratory fattening. The hummingbird liver appears to possess extraordinarily high capacities for fatty acid synthesis. The analysis of ＂known knowns＂ leads to identification of ＂known unknowns＂, e.g., the fates of dietary glucose and fructose, the regulation of fat metabolism and metabolic interactions between liver and adipose tissue. The history of science behooves recog- nition of ＂tmknown unknowns＂ that, when discovered serendipitously, might shed new light on fundamental mechanisms as well as human pathological conditions .展开更多
基金Supported by the National Natural Science Foundation of China(81373465)
文摘Long-chain acyl coenzyme A synthetase(ACSL) is a member of the synthetase family encoded by a multigene family;it plays an important role in the absorption and transport of fatty acid.Here we review the roles of ACSL in the regulating absorption and transport of fatty acid,as well as the connection between ACSL and some metabolic diseases.
文摘Fatty acid synthase （FAS） attracts more and more attention recently as a potential target for metabolic syndrome,such as cancer, obesity, diabetes and cerebrovascular disease. FAS inhibitors are widely existed in plants, consisting of diversiform compounds. These inhibitors exist not only in herbs also in many plant foods, such as teas, allium vegetables and some fruits. These effective components include gallated catechins, theaflavins,flavonoids, condensed and hydrolysable tannins, thioethers,pentacyclic triterpenes, stilbene derivatives, etc, and they target at the different domains of FAS, showing different inhibitory mechanisms. Interestingly, these FAS inhibitor-contained herbs and plant foods and their effective components are commonly related to the prevention of metabolic syndromes including fatreducing and depression of cancer. From biochemical angle,FAS can control the balance between energy provision and fat production. Some studies have shown that the effects of those effective components in plants on metabolic syndromes are mediated by inhibiting FAS. This suggests that FAS plays a critical role in the regulation of energy metabolism, and the FAS inhibitors from plants have significant potential application value in the treatment and prevention of metabolic syndromes.
基金supported by the National Key R&D Program of China(2018YFA0506900,2018YFA0800901)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12030211)the National Natural Science Foundation of China(31671226,31871194)。
文摘Acyl-coenzyme A thioesters(acyl-CoAs)denote a key class of intermediary metabolites that lies at the hub of major metabolic pathways.The great diversity in polarity between short-and long-chain acylCoAs makes it technically challenging to cover an inclusive range of acyl-CoAs within a single method.Levels of acyl-carnitines,which function to convey fatty acyls into mitochondria matrix forβ-oxidation,indicate the efficiency of mitochondrial import and utilization of corresponding acyl-CoAs.Herein,we report a robust,integrated platform to allow simultaneous quantitation of endogenous acyl-CoAs and acyl-carnitines.Using this method,we monitored changes in intermediary lipid profiles across Drosophila development under control(ND)and high-fat diet(HFD).We observed specific accumulations of medium-chain(C8-C12)and long-chain(≥C16)acyl-carnitines distinct to L3 larval and pupal stages,respectively.These observations suggested development-specific,chain length-dependent disparity in metabolic fates of acyl-CoAs across Drosophila development,which was validated by deploying the same platform to monitor isotope incorporation introduced from labelled 12:0 and 16:0 fatty acids into extra-and intra-mitochondrial acyl-CoA pools.We found that pupal mitochondria preferentially import and oxidise C12:0-CoAs(accumulated as C12:0-carnitines in L3 stage)over C16:0-CoAs.Preferential oxidation of medium-chain acyl-CoAs limits mitochondrial utilization of long-chain acyl-CoAs(C16-C18),leading to pupal-specific accumulation of long-chain acyl-carnitines mediated by enhanced CPT1-6 A activity.HFD skewed C16:0-CoAs towards catabolism over anabolism in pupa,thereby adversely affecting overall development.Our developed platform emphasizes the importance of integrating biological knowledge in the design of pathway-oriented platforms to derive maximal physiological insights from analysis of complex biological systems.
基金I am deeply grateful to EW. Hochachka, C.L. Gass, K.C. Welch, Jr., J.R.B. Lighton, C. Martinez del Rio and O. Mathieu-Costello for their contributions to the research that led to the ideas presented and questions raised in this paper. Research on which this article is based was funded by the U.S. National Science Foundation （IOB 0517694）.
文摘Hummingbird migration is a remarkable feat, given the small body sizes of migratory species, their high metabolic rates during flight and the long distances traveled using fat to fuel the effort. Equally remarkable is the ability of premigratory hummingbirds in the wild to accumulate fat, synthesized from sugar, at rates as high as 10% of body mass per day. This paper summarizes, using Rumsfeldian terminology, ＂known knowns＂ concerning the energetics of hummingbird migration and premi- gratory fattening. Energy metabolism during hover-feeding on floral nectar is fueled directly by dietary sugar through the path- way recently named the ＂sugar oxidation cascade＂. However, flight without feeding for more than a few minutes requires shifting to fat as a fuel. It is proposed that behavior and metabolic fuel choice are coadapted to maximize the rate of fat deposition during premigratory fattening. The hummingbird liver appears to possess extraordinarily high capacities for fatty acid synthesis. The analysis of ＂known knowns＂ leads to identification of ＂known unknowns＂, e.g., the fates of dietary glucose and fructose, the regulation of fat metabolism and metabolic interactions between liver and adipose tissue. The history of science behooves recog- nition of ＂tmknown unknowns＂ that, when discovered serendipitously, might shed new light on fundamental mechanisms as well as human pathological conditions .
