Obesity is considered an epidemic often accompanied by insulin resistance (IR). Heat treatment (HT) has been shown to prevent high-fat diet-induced IR in skeletal muscle, but the underlying mechanisms are poorly understood. In this study, we discovered that high temperature alleviated the hallmarks of obesity by promoting glycogen synthesis and lowering blood glucose levels in skeletal muscle tissue (SMT). Additionally, HT maintained the decay phase of heat shock factor 1 (HSF1), leading to the activation of gene expression of heat shock proteins (HSPs), which contributed to the alleviation of IR in SMT of diet-induced obese (DIO) mice. Metabolomics and lipidomics analyses showed that HT promoted ceramide (Cer) breakdown, resulting in an elevation of both sphingomyelin (SM) and sphingosine, which further contributed to the amelioration of IR in SMT of DIO mice. Importantly, the increase in sphingosine was attributed to the heightened expression of the acid ceramidase N-acylsphingosine amidohydrolase 1 (ASAH1), and the inhibition of ASAH1 attenuated HT-relieved IR in SMT of DIO mice. Surprisingly, high temperature increased the composition of Cer and cholesteryl ester in lipid droplets of skeletal muscle cells. This not only helped alleviate IR but also prevented lipotoxicity in SMT of DIO mice. These findings revealed a previously unknown connection between a high-temperature environment and sphingolipid metabolism in obesity, suggesting that high temperature can improve IR by promoting Cer catabolism in SMT of obese mice.
肥胖被认为是一种流行病，往往伴随着胰岛素抵抗（IR）。热处理（HT）已被证明能防止高脂饮食诱导的骨骼肌胰岛素抵抗，但其潜在机制却鲜为人知。在这项研究中，我们发现高温能促进糖原合成并降低骨骼肌组织（SMT）中的血糖水平，从而减轻肥胖症的特征。此外，高温还能维持热休克因子1（HSF1）的衰变阶段，从而激活热休克蛋白（HSPs）的基因表达，这有助于减轻饮食诱导肥胖（DIO）小鼠骨骼肌组织中的IR。代谢组学和脂质组学分析表明，高温促进了神经酰胺（Cer）的分解，导致鞘磷脂（SM）和鞘氨醇的增加，这进一步促进了DIO小鼠SMT中IR的改善。重要的是，鞘氨醇的增加归因于酸性神经氨酸酶 N-酰鞘氨醇酰胺水解酶 1（ASAH1）表达的增加，抑制 ASAH1 可减轻高温缓解的 DIO 小鼠 SMT 的 IR。令人惊讶的是，高温增加了骨骼肌细胞脂滴中Cer和胆固醇酯的成分。这不仅有助于缓解IR，还能防止DIO小鼠SMT的脂毒性。这些发现揭示了高温环境与肥胖症鞘脂代谢之间之前未知的联系，表明高温可以通过促进肥胖小鼠SMT中Cer的分解代谢来改善IR。
{"title":"High temperature ameliorates high-fat diet-induced obesity by promoting ceramide breakdown in skeletal muscle tissue","authors":"Qiankun Wang, Lupeng Chen, Junzhi Zhang, Yue Liu, Yi Jin, Jian Wu, Zhuqing Ren","doi":"10.1093/lifemeta/loae012","DOIUrl":"https://doi.org/10.1093/lifemeta/loae012","url":null,"abstract":"\u0000 Obesity is considered an epidemic often accompanied by insulin resistance (IR). Heat treatment (HT) has been shown to prevent high-fat diet-induced IR in skeletal muscle, but the underlying mechanisms are poorly understood. In this study, we discovered that high temperature alleviated the hallmarks of obesity by promoting glycogen synthesis and lowering blood glucose levels in skeletal muscle tissue (SMT). Additionally, HT maintained the decay phase of heat shock factor 1 (HSF1), leading to the activation of gene expression of heat shock proteins (HSPs), which contributed to the alleviation of IR in SMT of diet-induced obese (DIO) mice. Metabolomics and lipidomics analyses showed that HT promoted ceramide (Cer) breakdown, resulting in an elevation of both sphingomyelin (SM) and sphingosine, which further contributed to the amelioration of IR in SMT of DIO mice. Importantly, the increase in sphingosine was attributed to the heightened expression of the acid ceramidase N-acylsphingosine amidohydrolase 1 (ASAH1), and the inhibition of ASAH1 attenuated HT-relieved IR in SMT of DIO mice. Surprisingly, high temperature increased the composition of Cer and cholesteryl ester in lipid droplets of skeletal muscle cells. This not only helped alleviate IR but also prevented lipotoxicity in SMT of DIO mice. These findings revealed a previously unknown connection between a high-temperature environment and sphingolipid metabolism in obesity, suggesting that high temperature can improve IR by promoting Cer catabolism in SMT of obese mice.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140748777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.1093/lifemeta/loae007
John R. Speakman
{"title":"Results of the Second Life Metabolism Travel Awards 2024","authors":"John R. Speakman","doi":"10.1093/lifemeta/loae007","DOIUrl":"https://doi.org/10.1093/lifemeta/loae007","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140224482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-14DOI: 10.1093/lifemeta/loae010
Zhen Cao, Lei Lei, Ziyun Zhou, Shimeng Xu, Linlin Wang, Weikang Gong, Qi Zhang, Bin Pan, Gaoxin Zhang, Quan Yuan, Liujuan Cui, Min Zheng, Tao Xu, You Wang, Shuyan Zhang, Pingsheng Liu
It is crucial to understand the glucose control within our bodies. Bariatric/metabolic surgeries, including laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB), provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes (T2D). For the first time, a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics. Apolipoprotein A-IV (apoA-IV) was revealed to be increased dramatically in diabetic obese patients following LSG, and a similar effect was observed in patients after RYGB surgery. Moreover, recombinant protein apoA-IV treatment was proven to enhance insulin secretion in isolated human islets. These results showed that apoA-IV may play a crucial role in glycemic control in humans, potentially through enhancing insulin secretion in human islets. ApoA-IV was further shown to enhance energy expenditure and improve glucose tolerance in diabetic rodents, through stimulating glucose-dependent insulin secretion in pancreatic β cells, partially via Gαs-coupled GPCR/cAMP (G protein-coupled receptor-cyclic adenosine monophosphate) signaling. Furthermore, T55−121, truncated peptide 55−121 of apoA-IV, was discovered to mediate the function of apoA-IV. These collective findings contribute to our understanding of the relationship between apoA-IV and glycemic control, highlighting its potential as a biomarker or therapeutic target in managing and improving glucose regulation.
{"title":"Apolipoprotein A-IV and its derived peptide, T55−121, improve glycemic control and increase energy expenditure","authors":"Zhen Cao, Lei Lei, Ziyun Zhou, Shimeng Xu, Linlin Wang, Weikang Gong, Qi Zhang, Bin Pan, Gaoxin Zhang, Quan Yuan, Liujuan Cui, Min Zheng, Tao Xu, You Wang, Shuyan Zhang, Pingsheng Liu","doi":"10.1093/lifemeta/loae010","DOIUrl":"https://doi.org/10.1093/lifemeta/loae010","url":null,"abstract":"\u0000 It is crucial to understand the glucose control within our bodies. Bariatric/metabolic surgeries, including laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB), provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes (T2D). For the first time, a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics. Apolipoprotein A-IV (apoA-IV) was revealed to be increased dramatically in diabetic obese patients following LSG, and a similar effect was observed in patients after RYGB surgery. Moreover, recombinant protein apoA-IV treatment was proven to enhance insulin secretion in isolated human islets. These results showed that apoA-IV may play a crucial role in glycemic control in humans, potentially through enhancing insulin secretion in human islets. ApoA-IV was further shown to enhance energy expenditure and improve glucose tolerance in diabetic rodents, through stimulating glucose-dependent insulin secretion in pancreatic β cells, partially via Gαs-coupled GPCR/cAMP (G protein-coupled receptor-cyclic adenosine monophosphate) signaling. Furthermore, T55−121, truncated peptide 55−121 of apoA-IV, was discovered to mediate the function of apoA-IV. These collective findings contribute to our understanding of the relationship between apoA-IV and glycemic control, highlighting its potential as a biomarker or therapeutic target in managing and improving glucose regulation.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140242935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atherosclerosis is the major contributor to cardiovascular mortality worldwide. Alternate day fasting (ADF) has gained growing attention due to its metabolic benefits. However, the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models. The present study was designed to investigate the effect of ADF on atherosclerosis in apolipoprotein E-deficient (Apoe−/−) mice. Eleven-week-old male Apoe−/− mice fed with Western diet (WD) were randomly grouped into ad libitum (AL) group and ADF group, and ADF aggravated both the early and advanced atherosclerotic lesion formation, which might be due to the disturbed cholesterol profiles caused by ADF intervention. ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response (ISR) in the liver. The hepatic expression of activating transcription factor 3 (ATF3) was suppressed in mice treated with ADF and hepatocyte-specific overexpression of ATF3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe−/− mice. Moreover, the expression of ATF3 could be regulated by Krüppel-like factor 6 (KLF6) and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway. In conclusion, ADF aggravates atherosclerosis progression in Apoe−/− mice fed on WD. ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6, subsequently inhibiting ATF3 expression. The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe−/− mice. The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.
{"title":"Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe\u0000 −/− mice","authors":"Yajuan Deng, Xiaoyu Yang, Xueru Ye, Youwen Yuan, Yanan Zhang, Fei Teng, Danming You, Xuan Zhou, Wenhui Liu, Kangli Li, Shenjian Luo, Zhi Yang, Ruxin Chen, Guojun Shi, Jin Li, Huijie Zhang","doi":"10.1093/lifemeta/loae009","DOIUrl":"https://doi.org/10.1093/lifemeta/loae009","url":null,"abstract":"\u0000 Atherosclerosis is the major contributor to cardiovascular mortality worldwide. Alternate day fasting (ADF) has gained growing attention due to its metabolic benefits. However, the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models. The present study was designed to investigate the effect of ADF on atherosclerosis in apolipoprotein E-deficient (Apoe−/−) mice. Eleven-week-old male Apoe−/− mice fed with Western diet (WD) were randomly grouped into ad libitum (AL) group and ADF group, and ADF aggravated both the early and advanced atherosclerotic lesion formation, which might be due to the disturbed cholesterol profiles caused by ADF intervention. ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response (ISR) in the liver. The hepatic expression of activating transcription factor 3 (ATF3) was suppressed in mice treated with ADF and hepatocyte-specific overexpression of ATF3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe−/− mice. Moreover, the expression of ATF3 could be regulated by Krüppel-like factor 6 (KLF6) and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway. In conclusion, ADF aggravates atherosclerosis progression in Apoe−/− mice fed on WD. ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6, subsequently inhibiting ATF3 expression. The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe−/− mice. The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140260034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-02DOI: 10.1093/lifemeta/loae006
Zhi-Tian Chen, Zhi-Xuan Weng, Jiandie D. Lin, Zhuo-Xian Meng
Skeletal muscle plays a vital role in the regulation of systemic metabolism, partly through its secretion of endocrine factors which are collectively known as myokines. Altered myokine levels are associated with metabolic diseases, such as type 2 diabetes (T2D). The significance of interorgan crosstalk, particularly through myokines, has emerged as a fundamental aspect of nutrient and energy homeostasis. However, a comprehensive understanding of myokine biology in the setting of obesity and T2D remains a major challenge. In this review, we discuss the regulation and biological functions of key myokines that have been extensively studied during the past two decades, namely interleukin 6 (IL-6), irisin, myostatin (MSTN), growth differentiation factor 11 (GDF11), fibroblast growth factor 21 (FGF21), apelin, brain-derived neurotrophic factor (BDNF), meteorin-like (Metrnl), secreted protein acidic and rich in cysteine (SPARC), β-aminoisobutyric acid (BAIBA), Musclin, and Dickkopf-3 (Dkk3). Related to these, we detail the role of exercise in myokine expression and secretion together with their contributions to metabolic physiology and disease. Despite significant advancements in myokine research, many myokines remain challenging to measure accurately and investigate thoroughly. Hence, new research techniques and detection methods should be developed and rigorously tested. Therefore, developing a comprehensive perspective on myokine biology is crucial, as this will likely offer new insights into the pathophysiological mechanisms underlying obesity and T2D and may reveal novel targets for therapeutic interventions.
{"title":"Myokines: metabolic regulation in obesity and type 2 diabetes","authors":"Zhi-Tian Chen, Zhi-Xuan Weng, Jiandie D. Lin, Zhuo-Xian Meng","doi":"10.1093/lifemeta/loae006","DOIUrl":"https://doi.org/10.1093/lifemeta/loae006","url":null,"abstract":"\u0000 Skeletal muscle plays a vital role in the regulation of systemic metabolism, partly through its secretion of endocrine factors which are collectively known as myokines. Altered myokine levels are associated with metabolic diseases, such as type 2 diabetes (T2D). The significance of interorgan crosstalk, particularly through myokines, has emerged as a fundamental aspect of nutrient and energy homeostasis. However, a comprehensive understanding of myokine biology in the setting of obesity and T2D remains a major challenge. In this review, we discuss the regulation and biological functions of key myokines that have been extensively studied during the past two decades, namely interleukin 6 (IL-6), irisin, myostatin (MSTN), growth differentiation factor 11 (GDF11), fibroblast growth factor 21 (FGF21), apelin, brain-derived neurotrophic factor (BDNF), meteorin-like (Metrnl), secreted protein acidic and rich in cysteine (SPARC), β-aminoisobutyric acid (BAIBA), Musclin, and Dickkopf-3 (Dkk3). Related to these, we detail the role of exercise in myokine expression and secretion together with their contributions to metabolic physiology and disease. Despite significant advancements in myokine research, many myokines remain challenging to measure accurately and investigate thoroughly. Hence, new research techniques and detection methods should be developed and rigorously tested. Therefore, developing a comprehensive perspective on myokine biology is crucial, as this will likely offer new insights into the pathophysiological mechanisms underlying obesity and T2D and may reveal novel targets for therapeutic interventions.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140082259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-28DOI: 10.1093/lifemeta/loae005
Qingran Kong, Shaorong Gao
The dynamic changes in lipids during early embryonic development in mammals have not yet been comprehensively investigated. In a recent paper published in Nature Cell Biology, Jin Zhang et al. reported the dynamic lipid landscapes during preimplantation embryonic development in mice and humans. They highlight the crucial role of lipid unsaturation in regulating embryogenesis.
{"title":"Lipidomic remodeling during mammalian preimplantation embryonic development","authors":"Qingran Kong, Shaorong Gao","doi":"10.1093/lifemeta/loae005","DOIUrl":"https://doi.org/10.1093/lifemeta/loae005","url":null,"abstract":"\u0000 The dynamic changes in lipids during early embryonic development in mammals have not yet been comprehensively investigated. In a recent paper published in Nature Cell Biology, Jin Zhang et al. reported the dynamic lipid landscapes during preimplantation embryonic development in mice and humans. They highlight the crucial role of lipid unsaturation in regulating embryogenesis.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140419725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2023-12-08DOI: 10.1093/lifemeta/load048
Jameel Barkat Lone, Jonathan Z Long, Katrin J Svensson
The endocrine system is a fundamental type of long-range cell-cell communication that is important for maintaining metabolism, physiology, and other aspects of organismal homeostasis. Endocrine signaling is mediated by diverse blood-borne ligands, also called hormones, including metabolites, lipids, steroids, peptides, and proteins. The size and structure of these hormones are fine-tuned to make them bioactive, responsive, and adaptable to meet the demands of changing environments. Why has nature selected such diverse ligand types to mediate communication in the endocrine system? What is the chemical, signaling, or physiologic logic of these ligands? What fundamental principles from our knowledge of endocrine communication can be applied as we continue as a field to uncover additional new circulating molecules that are claimed to mediate long-range cell and tissue crosstalk? This review provides a framework based on the biochemical logic behind this crosstalk with respect to their chemistry, temporal regulation in physiology, specificity, signaling actions, and evolutionary development.
{"title":"Size matters: the biochemical logic of ligand type in endocrine crosstalk.","authors":"Jameel Barkat Lone, Jonathan Z Long, Katrin J Svensson","doi":"10.1093/lifemeta/load048","DOIUrl":"10.1093/lifemeta/load048","url":null,"abstract":"<p><p>The endocrine system is a fundamental type of long-range cell-cell communication that is important for maintaining metabolism, physiology, and other aspects of organismal homeostasis. Endocrine signaling is mediated by diverse blood-borne ligands, also called hormones, including metabolites, lipids, steroids, peptides, and proteins. The size and structure of these hormones are fine-tuned to make them bioactive, responsive, and adaptable to meet the demands of changing environments. Why has nature selected such diverse ligand types to mediate communication in the endocrine system? What is the chemical, signaling, or physiologic logic of these ligands? What fundamental principles from our knowledge of endocrine communication can be applied as we continue as a field to uncover additional new circulating molecules that are claimed to mediate long-range cell and tissue crosstalk? This review provides a framework based on the biochemical logic behind this crosstalk with respect to their chemistry, temporal regulation in physiology, specificity, signaling actions, and evolutionary development.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-20DOI: 10.1093/lifemeta/loae003
Yang Liu, S. Qian, Yang Tang, Qi-Qun Tang
In addition to their pivotal roles in energy storage and expenditure, adipose tissues play a crucial part in the secretion of bioactive molecules, including peptides, lipids, metabolites, and extracellular vesicles, in response to physiological stimulation and metabolic stress. These secretory factors, through autocrine and paracrine mechanisms, regulate various processes within adipose tissues. These processes include adipogenesis, glucose and lipid metabolism, inflammation, and adaptive thermogenesis, all of which are essential for the maintenance of the balance and functionality of the adipose tissue micro-environment. A subset of these adipose-derived secretory factors can enter the circulation and target the distant tissues to regulate appetite, cognitive function, energy expenditure, insulin secretion and sensitivity, gluconeogenesis, cardiovascular remodeling, and exercise capacity. In this review, we highlight the role of adipose-derived secretory factors and their signaling pathways in modulating metabolic homeostasis. Furthermore, we delve into the alterations in both the content and secretion processes of these factors under various physiological and pathological conditions, shedding light on potential pharmacological treatment strategies for related diseases.
{"title":"The secretory function of adipose tissues in metabolic regulation","authors":"Yang Liu, S. Qian, Yang Tang, Qi-Qun Tang","doi":"10.1093/lifemeta/loae003","DOIUrl":"https://doi.org/10.1093/lifemeta/loae003","url":null,"abstract":"\u0000 In addition to their pivotal roles in energy storage and expenditure, adipose tissues play a crucial part in the secretion of bioactive molecules, including peptides, lipids, metabolites, and extracellular vesicles, in response to physiological stimulation and metabolic stress. These secretory factors, through autocrine and paracrine mechanisms, regulate various processes within adipose tissues. These processes include adipogenesis, glucose and lipid metabolism, inflammation, and adaptive thermogenesis, all of which are essential for the maintenance of the balance and functionality of the adipose tissue micro-environment. A subset of these adipose-derived secretory factors can enter the circulation and target the distant tissues to regulate appetite, cognitive function, energy expenditure, insulin secretion and sensitivity, gluconeogenesis, cardiovascular remodeling, and exercise capacity. In this review, we highlight the role of adipose-derived secretory factors and their signaling pathways in modulating metabolic homeostasis. Furthermore, we delve into the alterations in both the content and secretion processes of these factors under various physiological and pathological conditions, shedding light on potential pharmacological treatment strategies for related diseases.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139524215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-18DOI: 10.1093/lifemeta/loae004
Jie Li, Yue Dong, Tianxing Zhou, He Tian, Xiahe Huang, Yong Q Zhang, Yingchun Wang, S. Lam, G. Shui
Interorgan lipid transport is crucial for organism development and the maintenance of physiological function. Here, we demonstrate that Drosophila long-chain acyl-CoA synthetase (dAcsl), which catalyzes the conversion of fatty acids into acyl-coenzyme As (acyl-CoAs), plays a critical role in regulating systemic lipid homeostasis. dAcsl deficiency in the fat body leads to the ectopic accumulation of neutral lipids in the gut, along with significantly reduced lipoprotein contents in both the fat body and hemolymph. The aberrant phenotypes were rescued by fat body-specific overexpression of apolipophorin. A multi-omics investigation comprising lipidomics, metabolomics, and proteomics in conjunction with genetic screening revealed that glycosylation processes were suppressed in dAcsl knockdowns. Overexpression of CG9035, human ortholog of which is implicated in the congenital disorder of glycosylation, ameliorated gut lipid accumulation in Drosophila. Aberrant lipoprotein glycosylation led to accelerated proteasome-related degradation and induced ER stress in dAcsl knockdown flies, impairing lipoprotein release into the circulation which compromised interorgan lipid transport between the fat body and the gut. Inhibition of ubiquitin-proteasome-dependent degradation alleviated the phenotype of gut ectopic fat accumulation in dAcsl knockdowns. Finally, we verified that ACSL4, the human homolog of dAcsl, also regulated lipoprotein levels in HepG2 cells, indicating that the role of dAcsl in modulating lipoprotein secretion and systemic lipid homeostasis is possibly conserved in humans.
{"title":"Long-chain acyl-CoA synthetase regulates systemic lipid homeostasis via glycosylation-dependent lipoprotein production","authors":"Jie Li, Yue Dong, Tianxing Zhou, He Tian, Xiahe Huang, Yong Q Zhang, Yingchun Wang, S. Lam, G. Shui","doi":"10.1093/lifemeta/loae004","DOIUrl":"https://doi.org/10.1093/lifemeta/loae004","url":null,"abstract":"\u0000 Interorgan lipid transport is crucial for organism development and the maintenance of physiological function. Here, we demonstrate that Drosophila long-chain acyl-CoA synthetase (dAcsl), which catalyzes the conversion of fatty acids into acyl-coenzyme As (acyl-CoAs), plays a critical role in regulating systemic lipid homeostasis. dAcsl deficiency in the fat body leads to the ectopic accumulation of neutral lipids in the gut, along with significantly reduced lipoprotein contents in both the fat body and hemolymph. The aberrant phenotypes were rescued by fat body-specific overexpression of apolipophorin. A multi-omics investigation comprising lipidomics, metabolomics, and proteomics in conjunction with genetic screening revealed that glycosylation processes were suppressed in dAcsl knockdowns. Overexpression of CG9035, human ortholog of which is implicated in the congenital disorder of glycosylation, ameliorated gut lipid accumulation in Drosophila. Aberrant lipoprotein glycosylation led to accelerated proteasome-related degradation and induced ER stress in dAcsl knockdown flies, impairing lipoprotein release into the circulation which compromised interorgan lipid transport between the fat body and the gut. Inhibition of ubiquitin-proteasome-dependent degradation alleviated the phenotype of gut ectopic fat accumulation in dAcsl knockdowns. Finally, we verified that ACSL4, the human homolog of dAcsl, also regulated lipoprotein levels in HepG2 cells, indicating that the role of dAcsl in modulating lipoprotein secretion and systemic lipid homeostasis is possibly conserved in humans.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139614794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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