Trends in Endocrinology and Metabolism : TEM

Purine metabolism is one of the core biochemical processes essential for cell survival and function. During development, purines are involved in germ cell development, ovarian function, and pregnancy outcomes. Here, we discuss the relationships between purine metabolism and reproductive health, offering insights into the future directions of the field.

No abstract text is available yet for this article.

Accurate assessment of brown fat thermogenesis by non-invasive means remains challenging. Writing in Nature Metabolism, Cai et al. leverage the futile creatine cycling characteristic of thermogenic adipocytes to show that a type of magnetic resonance imaging (MRI) technique sensitive to endogenous creatine levels faithfully tracks brown fat thermogenesis in rodents and in humans.

Interactions between the gut microbiome, nutrients, drugs, and host physiology are inherently complex. Gut microbes contribute significantly towards host homeostasis and can modulate host-targeted drugs, affecting therapeutic outcomes. Finding ways to harness the gut microbiome to improve drug efficacy can be a promising strategy to advance precision medicine.

Metformin, an oral antihyperglycemic drug that has been in use for over 60 years, remains a first-line therapy for type 2 diabetes (T2D). Numerous studies have suggested that metformin promotes health benefits beyond T2D management, including weight loss, cancer prevention and treatment, and anti-aging, through several proposed mechanistic targets. Here we discuss the established effects of metformin and the progress made in identifying its direct targets. Additionally, we emphasize the importance of elucidating the structural bases of the drug and its direct targets...

Aging is a major risk factor for a variety of diseases, thus, translation of aging research into practical applications is driven by the unmet need for existing clinical therapeutic options. Basic and translational research efforts are converging at a critical stage, yielding insights into how fundamental aging mechanisms are used to identify promising geroprotectors or therapeutics. This review highlights several research areas from a clinical perspective, including senescent cell targeting, alleviation of inflammaging, and optimization of metabolism with endogenous metabolites or precursors...

Astrocytes, the predominant glial cell type in the mammalian brain, influence a wide variety of brain parameters including neuronal energy metabolism. Exciting recent studies have shown that obesity and diabetes can impact on astrocyte function. We review evidence that dysregulation of astrocytic lipid metabolism and glucose sensing contributes to dysregulation of whole-body energy balance, thermoregulation, and insulin sensitivity. In addition, we consider the overlooked topic of the sex-specific roles of astrocytes and their response to hormonal fluctuations that provide insights into sex differences in metabolic regulation...

Despite sharing incretin activity with glucagon-like peptide 1 (GLP-1), the development of gastric inhibitory polypeptide (GIP)-based drugs has been hindered by the minor effects of native GIP on appetite and body weight and genetic studies associating loss-of-function with reduced obesity. Yet, pharmacologically optimized GIP-based molecules have demonstrated profound weight lowering benefits of GIPR agonism when combined with GLP-1-based therapies, which has re-energized deeper exploration of the molecular mechanisms and downstream signaling of GIPR...

Nicotinamide adenine dinucleotide (NAD+ ) is an essential coenzyme for redox reactions and regulates cellular catabolic pathways. An intertwined relationship exists between NAD+ and mitochondria, with consequences for mitochondrial function. Dysregulation in NAD+ homeostasis can lead to impaired energetics and increased oxidative stress, contributing to the pathogenesis of cardiometabolic diseases. In this review, we explore how disruptions in NAD+ homeostasis impact mitochondrial function in various cardiometabolic diseases...

Liver diseases represent a growing global health challenge, and the increasing prevalence of obesity and metabolic disorders is set to exacerbate this crisis. To meet evolving regulatory demands, patient-specific in vitro liver models are essential for understanding disease mechanisms and developing new therapeutic approaches. Organoid models, which faithfully recapitulate liver biology, can be established from both non-malignant and malignant liver tissues, offering insight into various liver conditions, from acute injuries to chronic diseases and cancer...

Very-low-density lipoprotein (VLDL), a triglyceride-rich lipoprotein secreted by hepatocytes, is pivotal for supplying peripheral tissues with fatty acids for energy production. As if walking on a tightrope, perturbations in the balance of VLDL metabolism contribute to cardiometabolic dysfunction, promoting pathologies such as cardiovascular disease (CVD) or metabolic dysfunction-associated steatotic liver disease (MASLD). Despite the advent of lipid-lowering therapies, including statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, risks for cardiovascular events persist...

The widespread use of per- and polyfluoroalkyl substances (PFASs), and their resistance to degradation, renders human exposure to them inevitable. PFAS exposure disturbs endocrine function, potentially affecting cognitive development in newborns through thyroid dysfunction during pregnancy. Recent studies reveal varying male and female reproductive toxicity across PFAS classes, with alternative analogs affecting sperm parameters and legacy PFASs correlating with conditions like endometriosis. Metabolically, PFASs exposure is linked to metabolic disorders, including obesity, type 2 diabetes mellitus (T2DM), dyslipidemia, and liver toxicity, particularly in early childhood...

Our limited understanding of metabolic aging poses major challenges to comprehending the diverse cellular alterations that contribute to age-related decline, and to devising targeted interventions. This review provides insights into the heterogeneous nature of cellular metabolism during aging and its response to interventions, with a specific focus on cellular heterogeneity and its implications. By synthesizing recent findings using single-cell approaches, we explored the vulnerabilities of distinct cell types and key metabolic pathways...

Glucocorticoids (GCs) are potent anti-inflammatory drugs. A new study by Auger et al. found that GCs increase itaconate, an anti-inflammatory tricarboxylic acid (TCA) cycle intermediate, by promoting movement of cytosolic pyruvate dehydrogenase (PDH) to mitochondria. Itaconate was sufficient for mediating the anti-inflammatory effects of GCs in mice, overriding the notion that nuclear glucocorticoid receptor (GR) is necessary for inflammation inhibition.

Triglyceride-rich lipoproteins (TRLs) play essential roles in human health and disease by transporting bulk lipids into the circulation. This review summarizes the fundamental mechanisms and diverse factors governing lipoprotein production, secretion, and regulation. Emphasizing the broader implications for human health, we outline the intricate landscape of lipoprotein research and highlight the potential coordination between the biogenesis and transport of TRLs in physiology, particularly the unexpected coupling of metabolic enzymes and transport machineries...

As a result of a long evolutionary history, serotonin plays a variety of physiological roles, including neurological, cardiovascular, gastrointestinal, and endocrine functions. While many of these activities can be accommodated within the serotoninergic activity, recent findings have revealed an unsuspected role of serotonin in orchestrating host and microbial dialogue at the tryptophan dining table, to the benefit of local and systemic homeostasis. Herein we review the dual role of serotonin at the host-microbe interface and discuss how unraveling the interconnections among the host and microbial pathways of tryptophan degradation may help to accommodate the versatility of serotonin in physiology and pathology...

No abstract text is available yet for this article.

Individuals with excessive adipose tissue and type 2 diabetes mellitus (T2DM) face a heightened risk of cardiovascular morbidity and mortality. Metabolic surgery is an effective therapy for people with severe obesity to achieve significant weight loss. Additionally, metabolic surgery improves blood glucose levels and can lead to T2DM remission, reducing major adverse cardiovascular outcomes (MACE). Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are a class of medication that effectively reduce body weight and MACE in patients with T2DM...

Pregnancy is associated with physiological adaptations that affect virtually all organs, enabling the mother to support the growing fetus and placenta while withstanding the demands of pregnancy. As a result, mammalian pregnancy is a unique state that exerts paradoxical effects on maternal health. On one hand, the metabolic stress induced by pregnancy can accelerate aging and functional decline in organs. On the other hand, pregnancy activates metabolic programming and tissue regenerative responses that can reverse age-related impairments...

Microplastics and nanoplastics (MNPs) are being recognized as new cardiovascular risk factors, impacting vascular cell functions and exacerbating atherosclerosis through diverse mechanisms. However, the varied concentrations of MNPs detected in major cardiovascular tissues highlight the urgent need for standardized research methodologies to better understand their impact and inform future health guidelines.