Trends in Endocrinology and Metabolism最新文献

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.

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.

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.

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.

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.

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 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.

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.

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.