Pub Date : 2024-05-22DOI: 10.1016/j.tem.2024.04.021
Ruben Vazquez-Uribe, Karl Alex Hedin, Tine Rask Licht, Max Nieuwdorp, Morten O A Sommer
The rising prevalence of metabolic diseases calls for innovative treatments. Peptide-based drugs have transformed the management of conditions such as obesity and type 2 diabetes. Yet, challenges persist in oral delivery of these peptides. This review explores the potential of 'advanced microbiome therapeutics' (AMTs), which involve engineered microbes for delivery of peptides in situ, thereby enhancing their bioavailability. Preclinical work on AMTs has shown promise in treating animal models of metabolic diseases, including obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. Outstanding challenges toward realizing the potential of AMTs involve improving peptide expression, ensuring predictable colonization control, enhancing stability, and managing safety and biocontainment concerns. Still, AMTs have potential for revolutionizing the treatment of metabolic diseases, potentially offering dynamic and personalized novel therapeutic approaches.
{"title":"Advanced microbiome therapeutics as a novel modality for oral delivery of peptides to manage metabolic diseases.","authors":"Ruben Vazquez-Uribe, Karl Alex Hedin, Tine Rask Licht, Max Nieuwdorp, Morten O A Sommer","doi":"10.1016/j.tem.2024.04.021","DOIUrl":"https://doi.org/10.1016/j.tem.2024.04.021","url":null,"abstract":"<p><p>The rising prevalence of metabolic diseases calls for innovative treatments. Peptide-based drugs have transformed the management of conditions such as obesity and type 2 diabetes. Yet, challenges persist in oral delivery of these peptides. This review explores the potential of 'advanced microbiome therapeutics' (AMTs), which involve engineered microbes for delivery of peptides in situ, thereby enhancing their bioavailability. Preclinical work on AMTs has shown promise in treating animal models of metabolic diseases, including obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. Outstanding challenges toward realizing the potential of AMTs involve improving peptide expression, ensuring predictable colonization control, enhancing stability, and managing safety and biocontainment concerns. Still, AMTs have potential for revolutionizing the treatment of metabolic diseases, potentially offering dynamic and personalized novel therapeutic approaches.</p>","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":10.9,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-18DOI: 10.1016/j.tem.2024.04.017
S. Wculek, Stephan Forisch, Verónica Miguel, David Sancho
{"title":"Metabolic homeostasis of tissue macrophages across the lifespan","authors":"S. Wculek, Stephan Forisch, Verónica Miguel, David Sancho","doi":"10.1016/j.tem.2024.04.017","DOIUrl":"https://doi.org/10.1016/j.tem.2024.04.017","url":null,"abstract":"","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":10.9,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-18DOI: 10.1016/j.tem.2024.04.016
Aaron Novikoff, Timo D. Müller
{"title":"Antagonizing GIPR adds fire to the GLP-1R flame","authors":"Aaron Novikoff, Timo D. Müller","doi":"10.1016/j.tem.2024.04.016","DOIUrl":"https://doi.org/10.1016/j.tem.2024.04.016","url":null,"abstract":"","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":10.9,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1016/j.tem.2024.04.015
Megan R Teh, Andrew E Armitage, Hal Drakesmith
Iron deficiency is globally prevalent, causing an array of developmental, haematological, immunological, neurological, and cardiometabolic impairments, and is associated with symptoms ranging from chronic fatigue to hair loss. Within cells, iron is utilised in a variety of ways by hundreds of different proteins. Here, we review links between molecular activities regulated by iron and the pathophysiological effects of iron deficiency. We identify specific enzyme groups, biochemical pathways, cellular functions, and cell lineages that are particularly iron dependent. We provide examples of how iron deprivation influences multiple key systems and tissues, including immunity, hormone synthesis, and cholesterol metabolism. We propose that greater mechanistic understanding of how cellular iron influences physiological processes may lead to new therapeutic opportunities across a range of diseases.
{"title":"Why cells need iron: a compendium of iron utilisation.","authors":"Megan R Teh, Andrew E Armitage, Hal Drakesmith","doi":"10.1016/j.tem.2024.04.015","DOIUrl":"https://doi.org/10.1016/j.tem.2024.04.015","url":null,"abstract":"<p><p>Iron deficiency is globally prevalent, causing an array of developmental, haematological, immunological, neurological, and cardiometabolic impairments, and is associated with symptoms ranging from chronic fatigue to hair loss. Within cells, iron is utilised in a variety of ways by hundreds of different proteins. Here, we review links between molecular activities regulated by iron and the pathophysiological effects of iron deficiency. We identify specific enzyme groups, biochemical pathways, cellular functions, and cell lineages that are particularly iron dependent. We provide examples of how iron deprivation influences multiple key systems and tissues, including immunity, hormone synthesis, and cholesterol metabolism. We propose that greater mechanistic understanding of how cellular iron influences physiological processes may lead to new therapeutic opportunities across a range of diseases.</p>","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":10.9,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-14DOI: 10.1016/j.tem.2024.04.012
Elizabeth S Anaya, Evelyn L de Groot, John P Lydon, Stephanie A Pangas, Sean M Hartig
Body composition impacts female fertility and there are established relationships between adipose tissue and the reproductive system. Maintaining functional adipose tissue is vital for meeting the energetic demands during the reproductive process, from ovulation to delivery and lactation. White adipose tissue (WAT) shows plastic responses to daily physiology and secretes diverse adipokines that affect the hypothalamic-pituitary-ovarian axis, but many other interorgan interactions remain to be determined. This review summarizes the current state of research on the dialogue between WAT and the female reproductive system, focusing on the impact of this crosstalk on ovarian and endometrial factors essential for fecundity.
{"title":"Contributions of white adipose tissue to energy requirements for female reproduction.","authors":"Elizabeth S Anaya, Evelyn L de Groot, John P Lydon, Stephanie A Pangas, Sean M Hartig","doi":"10.1016/j.tem.2024.04.012","DOIUrl":"https://doi.org/10.1016/j.tem.2024.04.012","url":null,"abstract":"<p><p>Body composition impacts female fertility and there are established relationships between adipose tissue and the reproductive system. Maintaining functional adipose tissue is vital for meeting the energetic demands during the reproductive process, from ovulation to delivery and lactation. White adipose tissue (WAT) shows plastic responses to daily physiology and secretes diverse adipokines that affect the hypothalamic-pituitary-ovarian axis, but many other interorgan interactions remain to be determined. This review summarizes the current state of research on the dialogue between WAT and the female reproductive system, focusing on the impact of this crosstalk on ovarian and endometrial factors essential for fecundity.</p>","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":10.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-07DOI: 10.1016/j.tem.2024.04.014
Daniel M Marko, Meghan O Conn, Jonathan D Schertzer
Intermittent fasting (IF) modifies cell- and tissue-specific immunometabolic responses that dictate metabolic flexibility and inflammation during obesity and type 2 diabetes (T2D). Fasting forces periods of metabolic flexibility and necessitates increased use of different substrates. IF can lower metabolic inflammation and improve glucose metabolism without lowering obesity and can influence time-dependent, compartmentalized changes in immunity. Liver, adipose tissue, skeletal muscle, and immune cells communicate to relay metabolic and immune signals during fasting. Here we review the connections between metabolic and immune cells to explain the divergent effects of IF compared with classic caloric restriction (CR) strategies. We also explore how the immunometabolism of metabolic diseases dictates certain IF outcomes, where the gut microbiota triggers changes in immunity and metabolism during fasting.
间歇性禁食(IF)会改变细胞和组织特异性免疫代谢反应,这些反应决定了肥胖和 2 型糖尿病(T2D)期间的代谢灵活性和炎症。禁食迫使新陈代谢变得灵活,并需要增加对不同底物的使用。空腹能在不降低肥胖率的情况下降低代谢炎症和改善葡萄糖代谢,并能影响免疫力随时间发生的分区变化。在禁食期间,肝脏、脂肪组织、骨骼肌和免疫细胞会相互传递代谢和免疫信号。在此,我们回顾了代谢细胞和免疫细胞之间的联系,以解释 IF 与传统热量限制(CR)策略相比的不同效果。我们还探讨了代谢性疾病的免疫代谢是如何决定某些 IF 结果的,其中肠道微生物群在禁食期间引发了免疫和代谢的变化。
{"title":"Intermittent fasting influences immunity and metabolism.","authors":"Daniel M Marko, Meghan O Conn, Jonathan D Schertzer","doi":"10.1016/j.tem.2024.04.014","DOIUrl":"https://doi.org/10.1016/j.tem.2024.04.014","url":null,"abstract":"<p><p>Intermittent fasting (IF) modifies cell- and tissue-specific immunometabolic responses that dictate metabolic flexibility and inflammation during obesity and type 2 diabetes (T2D). Fasting forces periods of metabolic flexibility and necessitates increased use of different substrates. IF can lower metabolic inflammation and improve glucose metabolism without lowering obesity and can influence time-dependent, compartmentalized changes in immunity. Liver, adipose tissue, skeletal muscle, and immune cells communicate to relay metabolic and immune signals during fasting. Here we review the connections between metabolic and immune cells to explain the divergent effects of IF compared with classic caloric restriction (CR) strategies. We also explore how the immunometabolism of metabolic diseases dictates certain IF outcomes, where the gut microbiota triggers changes in immunity and metabolism during fasting.</p>","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":10.9,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-04DOI: 10.1016/j.tem.2024.04.013
Chae Won Kim, Hyun-Jin Kim, Heung Kyu Lee
Immune checkpoint blockade (ICB) is one of the leading immunotherapies, although a variable extent of resistance has been observed among patients and across cancer types. Among the efforts underway to overcome this challenge, the microbiome has emerged as a factor affecting the responsiveness and efficacy of ICB. Active research, facilitated by advances in sequencing techniques, is assessing the predominant influence of the intestinal microbiome, as well as the effects of the presence of an intratumoral microbiome. In this review, we describe recent findings from clinical trials, observational studies of human patients, and animal studies on the impact of the microbiome on the efficacy of ICB, highlighting the role of the intestinal and tumor microbiomes and the contribution of methodological advances in their study.
{"title":"Microbiome dynamics in immune checkpoint blockade.","authors":"Chae Won Kim, Hyun-Jin Kim, Heung Kyu Lee","doi":"10.1016/j.tem.2024.04.013","DOIUrl":"https://doi.org/10.1016/j.tem.2024.04.013","url":null,"abstract":"<p><p>Immune checkpoint blockade (ICB) is one of the leading immunotherapies, although a variable extent of resistance has been observed among patients and across cancer types. Among the efforts underway to overcome this challenge, the microbiome has emerged as a factor affecting the responsiveness and efficacy of ICB. Active research, facilitated by advances in sequencing techniques, is assessing the predominant influence of the intestinal microbiome, as well as the effects of the presence of an intratumoral microbiome. In this review, we describe recent findings from clinical trials, observational studies of human patients, and animal studies on the impact of the microbiome on the efficacy of ICB, highlighting the role of the intestinal and tumor microbiomes and the contribution of methodological advances in their study.</p>","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":10.9,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-04DOI: 10.1016/j.tem.2024.04.009
Ruonan Xu, Nemanja Vujić, Valentina Bianco, Isabel Reinisch, Dagmar Kratky, Jelena Krstic, Andreas Prokesch
Lipid-associated macrophages (LAMs) are phagocytic cells with lipid-handling capacity identified in various metabolic derangements. During disease development, they locate to atherosclerotic plaques, adipose tissue (AT) of individuals with obesity, liver lesions in steatosis and steatohepatitis, and the intestinal lamina propria. LAMs can also emerge in the metabolically demanding microenvironment of certain tumors. In this review, we discuss major questions regarding LAM recruitment, differentiation, and self-renewal, and, ultimately, their acute and chronic functional impact on the development of metabolic diseases. Further studies need to clarify whether and under which circumstances LAMs drive disease progression or resolution and how their phenotype can be modulated to ameliorate metabolic disorders.
{"title":"Lipid-associated macrophages between aggravation and alleviation of metabolic diseases.","authors":"Ruonan Xu, Nemanja Vujić, Valentina Bianco, Isabel Reinisch, Dagmar Kratky, Jelena Krstic, Andreas Prokesch","doi":"10.1016/j.tem.2024.04.009","DOIUrl":"https://doi.org/10.1016/j.tem.2024.04.009","url":null,"abstract":"<p><p>Lipid-associated macrophages (LAMs) are phagocytic cells with lipid-handling capacity identified in various metabolic derangements. During disease development, they locate to atherosclerotic plaques, adipose tissue (AT) of individuals with obesity, liver lesions in steatosis and steatohepatitis, and the intestinal lamina propria. LAMs can also emerge in the metabolically demanding microenvironment of certain tumors. In this review, we discuss major questions regarding LAM recruitment, differentiation, and self-renewal, and, ultimately, their acute and chronic functional impact on the development of metabolic diseases. Further studies need to clarify whether and under which circumstances LAMs drive disease progression or resolution and how their phenotype can be modulated to ameliorate metabolic disorders.</p>","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":10.9,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-02-07DOI: 10.1016/j.tem.2024.01.007
Krista A Varady, Mary-Claire Runchey, Sirimon Reutrakul, Alaina P Vidmar, Lisa S Chow
Most adults with type 1 diabetes (T1DM) are either overweight or obese. As such, dietary management is recommended as an adjunct to insulin treatment to improve glycemic control and facilitate weight loss in these patients. Time-restricted eating (TRE) is a form of intermittent fasting that offers a simplified approach to treating obesity in T1DM. TRE typically involves restricting eating to 6 to 10 h per day, with water and medications allowed outside the eating window. This review examines the efficacy of TRE and other fasting protocols in improving weight and glycemic control in patients with obesity and T1DM. This review will also evaluate the safety of these regimens and provide advice to clinicians on implementing intermittent fasting in T1DM.
{"title":"Clinical potential of fasting in type 1 diabetes.","authors":"Krista A Varady, Mary-Claire Runchey, Sirimon Reutrakul, Alaina P Vidmar, Lisa S Chow","doi":"10.1016/j.tem.2024.01.007","DOIUrl":"10.1016/j.tem.2024.01.007","url":null,"abstract":"<p><p>Most adults with type 1 diabetes (T1DM) are either overweight or obese. As such, dietary management is recommended as an adjunct to insulin treatment to improve glycemic control and facilitate weight loss in these patients. Time-restricted eating (TRE) is a form of intermittent fasting that offers a simplified approach to treating obesity in T1DM. TRE typically involves restricting eating to 6 to 10 h per day, with water and medications allowed outside the eating window. This review examines the efficacy of TRE and other fasting protocols in improving weight and glycemic control in patients with obesity and T1DM. This review will also evaluate the safety of these regimens and provide advice to clinicians on implementing intermittent fasting in T1DM.</p>","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-02-29DOI: 10.1016/j.tem.2024.02.003
Mona Mashayekhi, Bilgunay Ilkin Safa, Matthew S C Gonzalez, Sangwon F Kim, Justin B Echouffo-Tcheugui
Inflammation plays an essential role and is a common feature in the pathogenesis of many chronic diseases. The exact mechanisms through which sodium-glucose cotransporter-2 (SGLT2) inhibitors achieve their much-acclaimed clinical benefits largely remain unknown. In this review, we detail the systemic and tissue- or organ-specific anti-inflammatory effects of SGLT2 inhibitors using evidence from animal and human studies. We discuss the potential pathways through which SGLT2 inhibitors exert their anti-inflammatory effects, including oxidative stress, mitochondrial, and inflammasome pathways. Finally, we highlight the need for further investigation of the extent of the contribution of the anti-inflammatory effects of SGLT2 inhibition to improvements in cardiometabolic and renal outcomes in clinical studies.
{"title":"Systemic and organ-specific anti-inflammatory effects of sodium-glucose cotransporter-2 inhibitors.","authors":"Mona Mashayekhi, Bilgunay Ilkin Safa, Matthew S C Gonzalez, Sangwon F Kim, Justin B Echouffo-Tcheugui","doi":"10.1016/j.tem.2024.02.003","DOIUrl":"10.1016/j.tem.2024.02.003","url":null,"abstract":"<p><p>Inflammation plays an essential role and is a common feature in the pathogenesis of many chronic diseases. The exact mechanisms through which sodium-glucose cotransporter-2 (SGLT2) inhibitors achieve their much-acclaimed clinical benefits largely remain unknown. In this review, we detail the systemic and tissue- or organ-specific anti-inflammatory effects of SGLT2 inhibitors using evidence from animal and human studies. We discuss the potential pathways through which SGLT2 inhibitors exert their anti-inflammatory effects, including oxidative stress, mitochondrial, and inflammasome pathways. Finally, we highlight the need for further investigation of the extent of the contribution of the anti-inflammatory effects of SGLT2 inhibition to improvements in cardiometabolic and renal outcomes in clinical studies.</p>","PeriodicalId":54415,"journal":{"name":"Trends in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":11.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}