Trends Endocrinol Metab
· 2025 Jun · PMID 39701917
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Orosomucoids (ORMs) have historically been considered as carriers involved in drug and lipid delivery. However, recent studies indicate ORM2 as a hepatokine involved in metabolic regulation. Here, we highlight the functi...Orosomucoids (ORMs) have historically been considered as carriers involved in drug and lipid delivery. However, recent studies indicate ORM2 as a hepatokine involved in metabolic regulation. Here, we highlight the functions of ORM2 in controlling metabolic health and disease, focusing on its newly discovered regulatory mechanisms.
Perceived stress levels, prevalence of pregnancies complicated by metabolic disorders, and childhood obesity have been increasing steadily. We here propose a pathway integrating stress-responsive biological systems into...Perceived stress levels, prevalence of pregnancies complicated by metabolic disorders, and childhood obesity have been increasing steadily. We here propose a pathway integrating stress-responsive biological systems into the established effects of maternal diabetes and obesity during pregnancy, overall exerting a combined contribution to offspring adiposity risk.
When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, a...When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM and skeletal-muscle-related symptoms. In this opinion article we highlight intrinsic mitochondrial dysfunction, endothelial abnormalities, and a muscle fiber type shift towards a more glycolytic phenotype as main contributors to the reduced exercise capacity in long COVID. The mechanistic trigger for physical exercise to induce PEM is unknown, but rapid skeletal muscle tissue damage and intramuscular infiltration of immune cells contribute to PEM-related symptoms.
Tryptophan (Trp) metabolism is linked to health and disease, with indoleamine 2,3-dioxygenase 1 (IDO) being a key enzyme in its breakdown outside the liver. This process produces metabolites that influence metabolic and...Tryptophan (Trp) metabolism is linked to health and disease, with indoleamine 2,3-dioxygenase 1 (IDO) being a key enzyme in its breakdown outside the liver. This process produces metabolites that influence metabolic and inflammatory responses. A distinctive feature of the gut is its involvement in three major Trp catabolic pathways: the IDO-driven kynurenine pathway, bacteria-produced indoles, and serotonin. Dysregulation of these pathways is associated with gastrointestinal and chronic inflammatory diseases. Understanding these mechanisms could reveal how gut function affects overall systemic health and disease susceptibility. Here, we review current insights into Trp metabolism, its impact on host physiology and cardiometabolic diseases, and its role in the gut-periphery connection, highlighting its relevance for therapeutic innovation.
Trends Endocrinol Metab
· 2025 Aug · PMID 39694728
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Inter-organ communication (IOC) is a complex mechanism involved in maintaining metabolic homeostasis and healthy aging. Dysregulation of distinct forms of IOC is linked to metabolic derangements and age-related pathologi...Inter-organ communication (IOC) is a complex mechanism involved in maintaining metabolic homeostasis and healthy aging. Dysregulation of distinct forms of IOC is linked to metabolic derangements and age-related pathologies, implicating these processes as a potential target for therapeutic intervention to promote healthy aging. In this review, we delve into IOC mediated by hormonal signaling, circulating factors, organelle signaling, and neuronal networks and examine their roles in regulating metabolism and aging. Given the role of the hypothalamus as a high-order control center for aging and longevity, we particularly emphasize the importance of its communication with peripheral organs and pave the way for a better understanding of this critical machinery in metabolism and aging.
Citrin KM, Chaube B, Fernández-Hernando C
… +1 more, Suárez Y
Trends Endocrinol Metab
· 2025 Aug · PMID 39672762
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Endothelial cells (ECs) form the inner lining of blood vessels that is crucial for vascular function and homeostasis. They regulate vascular tone, oxidative stress, and permeability. Dysfunction leads to increased permea...Endothelial cells (ECs) form the inner lining of blood vessels that is crucial for vascular function and homeostasis. They regulate vascular tone, oxidative stress, and permeability. Dysfunction leads to increased permeability, leukocyte adhesion, and thrombosis. ECs undergo metabolic changes in conditions such as wound healing, cancer, atherosclerosis, and diabetes, and can influence disease progression. We discuss recent research that has revealed diverse intracellular metabolic pathways in ECs that are tailored to their functional needs, including lipid handling, glycolysis, and fatty acid oxidation (FAO). Understanding EC metabolic signatures in health and disease will be crucial not only for basic biology but can also be exploited when designing new therapies to target EC-related functions in different vascular diseases.
It has long been thought that the functional identity of mammalian brain neurons is programmed during development and remains stable throughout adult life; however, certain populations of neurons continue to express acti...It has long been thought that the functional identity of mammalian brain neurons is programmed during development and remains stable throughout adult life; however, certain populations of neurons continue to express active regulators of neuronal identity into adulthood. Prolonged exposure to diet-induced metabolic stress induces features of neuronal identity modification in adult mice, and maladaptive changes in neuronal identity maintenance have been linked to cognitive impairment in humans suffering from neurodegenerative diseases often associated with obesity. Here we discuss how, by unraveling the neurological roots of obesity, we may solve the puzzle of whether mammalian brain neurons retain identity plasticity into adulthood, while advancing knowledge of the pathogenic mechanisms at the interface of metabolic and neurodegenerative disorders.
Chen B, Meseguer D, Lenck S
… +2 more, Thomas JL, Schneeberger M
Trends Endocrinol Metab
· 2025 Aug · PMID 39638721
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The incorporation of the glymphatic clearance system in the study of brain physiology aids in the advancement of innovative diagnostic and treatment strategies for neurological disorders. Exploring the glymphatic system...The incorporation of the glymphatic clearance system in the study of brain physiology aids in the advancement of innovative diagnostic and treatment strategies for neurological disorders. Exploring the glymphatic system across (from) neurological and (to) metabolic diseases may provide a better link between obesity and neurological disorders. Recent studies indicate the role of metabolic dysfunction as a risk factor for cognitive decline and neurological disorders through the disruption of the glymphatic system. Further investigation into how metabolic dysfunction disrupts glymphatic homeostasis and the domino effects on the neurovascular landscape, including neurovascular uncoupling, cerebral blood flow disruptions, blood-brain barrier leakage, and demyelination, can provide mechanistic insights into the link between obesity and neurological disorders.
Obesity has become a global pandemic that is associated with a range of metabolic disorders. Traditional treatment options, such as lifestyle modification and anti-obesity medications, often exhibit limited efficacy and...Obesity has become a global pandemic that is associated with a range of metabolic disorders. Traditional treatment options, such as lifestyle modification and anti-obesity medications, often exhibit limited efficacy and can lead to long-term weight gain, especially upon discontinuation of the medication. Although bariatric surgery is effective, its accessibility is constrained, and only a small percentage of eligible patients receive this intervention. Over the past two decades, endoscopic bariatric and metabolic therapies (EBMTs) have emerged as minimally invasive and effective alternatives for managing obesity and its related comorbidities. This article reviews primary gastric and small bowel EBMTs, their mechanisms of action, key supporting literature, and the metabolic outcomes associated with each device and procedure.
Chen J, Markworth JF, Ferreira C
… +2 more, Zhang C, Kuang S
Trends Endocrinol Metab
· 2025 Jul · PMID 39613547
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Lipid droplets (LDs) are dynamic organelles that communicate with other cellular components to orchestrate energetic homeostasis and signal transduction. In skeletal muscle, the presence and importance of LDs have been w...Lipid droplets (LDs) are dynamic organelles that communicate with other cellular components to orchestrate energetic homeostasis and signal transduction. In skeletal muscle, the presence and importance of LDs have been widely studied in myofibers of both rodents and humans under physiological conditions and in metabolic disorders. However, the role of LDs in myogenic stem cells has only recently begun to be unveiled. In this review we briefly summarize the process of LD biogenesis and degradation in the most prevalent model. We then review recent knowledge on LDs in skeletal muscle and muscle stem cells. We further introduce advanced methodologies for LD imaging and mass spectrometry that have propelled our understanding of the dynamics and heterogeneity of LDs.
The Genes & Health study, an initiative focused on British-Pakistani and British-Bangladeshi volunteers, is at the forefront of diversifying genetic research and driving scientific innovation. Here, we explore how this s...The Genes & Health study, an initiative focused on British-Pakistani and British-Bangladeshi volunteers, is at the forefront of diversifying genetic research and driving scientific innovation. Here, we explore how this study has propelled scientific advancements and positively impacted communities, emphasizing its collaborative ethos, dedication to societal needs, and accomplishments.
Metabolic diseases, characterized by chronic low-grade inflammation, exhibit a compromised gut barrier allowing the translocation of bacteria-derived products to bloodstream and distant metabolic organs. Bacterial DNA ca...Metabolic diseases, characterized by chronic low-grade inflammation, exhibit a compromised gut barrier allowing the translocation of bacteria-derived products to bloodstream and distant metabolic organs. Bacterial DNA can be detected in metabolic tissues during the onset of these diseases, highlighting its role in the development of metabolic diseases. Extracellular vesicles (EVs) are involved in the delivery of bacterial DNA to the local tissues, and its sensing by the host triggers local and system inflammation. Understanding bacterial DNA translocation and its induced inflammation is crucial in deciphering metabolic disease pathways. Here, we delve into the mechanisms dictating the interaction between host physiology and bacterial DNA, focusing on its origin and delivery, host immune responses against it, and its roles in metabolic disorders.
Mitochondria must sense their environment to enable cells and organisms to adapt to diverse environments and survive during stress. However, during microbial infection, an evolutionary pressure since the inception of the...Mitochondria must sense their environment to enable cells and organisms to adapt to diverse environments and survive during stress. However, during microbial infection, an evolutionary pressure since the inception of the eukaryotic cell, these organelles are traditionally viewed as targets for microbes. In this opinion we consider the perspective that mitochondria are domesticated microbes that sense and guard their 'host' cell against pathogens. We explore potential mechanisms by which mitochondria detect intracellular pathogens and induce mitochondria-autonomous responses that activate cellular defenses.
Paternal health and exposure to adverse environments in the period prior to conception have a profound impact on future generations. Adversities such as stress, diet, and toxicants influence offspring health. Emerging ev...Paternal health and exposure to adverse environments in the period prior to conception have a profound impact on future generations. Adversities such as stress, diet, and toxicants influence offspring health. Emerging evidence indicates that epigenetic mechanisms including noncoding RNA, DNA methylation, and chromatin remodelling mediate these effects. Preclinical studies have contributed to advancing mechanistic understanding in the field; however, human research is limited and primarily observational. Here, we discuss the evidence linking paternal to offspring health and advocate for further research in this area, which may ultimately inform policy and healthcare guidelines to improve paternal preconception health and offspring outcomes.
Non-sugar sweeteners (NSS), low- or no-calorie alternatives to sugar, are marketed for weight loss and improved blood glucose control in people with diabetes. However, their health effects remain controversial. This revi...Non-sugar sweeteners (NSS), low- or no-calorie alternatives to sugar, are marketed for weight loss and improved blood glucose control in people with diabetes. However, their health effects remain controversial. This review provides a brief overview of sweet taste perception and summarizes experimental findings of the impact of NSS on cardiometabolic health in animal models and humans. We also review evidence suggesting that many NSS are not metabolically inert, highlighting the challenges in related human studies. Given the conflicting and unclear data on health outcomes, additional mechanistic studies, particularly in animal models, are necessary to clarify how NSS influence feeding behaviors and energy homoeostasis.
MicroRNAs (miRNAs) are noncoding RNA molecules that regulate gene expression post-transcriptionally and influence numerous biological processes. Aberrant miRNA expression is linked to diseases such as diabetes mellitus;...MicroRNAs (miRNAs) are noncoding RNA molecules that regulate gene expression post-transcriptionally and influence numerous biological processes. Aberrant miRNA expression is linked to diseases such as diabetes mellitus; indeed, miRNAs regulate pancreatic islet inflammation in both type 1 (T1D) and type 2 diabetes (T2D). Traditionally, miRNA research has focused on canonical sequences and offers a two-layer view - from expression to function. However, advances in RNA sequencing have revealed miRNA variants, called isomiRs, that arise from alternative processing or modifications of canonical sequences. This introduces a three-layer view - from expression, through sequence modifications, to function. We discuss the potential link between cellular stresses and isomiR biogenesis, and how this association could improve our knowledge of islet inflammation and dysfunction.
Previously characterized as inert fat depots, adipocytes are now recognized as dynamic mediators of inflammatory tone, metabolic health, and nutrient homeostasis. As endocrine organs, specialized depots of adipose tissue...Previously characterized as inert fat depots, adipocytes are now recognized as dynamic mediators of inflammatory tone, metabolic health, and nutrient homeostasis. As endocrine organs, specialized depots of adipose tissue engage in crosstalk between the gut, liver, pancreas, and brain to coordinate appetite, thermogenesis, and ultimately body weight. These functions are tightly linked to the inflammatory status of adipose tissue, which is in turn influenced by the health of the gut microbiome. Here, we review recent findings linking specific gut microbes and their secreted factors, including recently identified elements such as bacterial extracellular vesicles, to the functional status of adipocytes. We conclude that further study may generate novel approaches for treating obesity and metabolic disease.
Recent genetic studies have implicated an active role for intrahepatic lipid accumulation in the pathogenesis of both polycystic ovary syndrome (PCOS) and cardiovascular disease. These new insights may provide novel (non...Recent genetic studies have implicated an active role for intrahepatic lipid accumulation in the pathogenesis of both polycystic ovary syndrome (PCOS) and cardiovascular disease. These new insights may provide novel (non)pharmacological opportunities for the prevention and treatment of PCOS and cardiovascular disease at both the societal and clinical level.