Trends in Endocrinology and Metabolism最新文献

Amyotrophic lateral sclerosis (ALS) is a complex and rapidly progressive motor neuron disorder with a fatal outcome. Despite the remarkable progress in understanding ALS pathophysiology, which has significantly contributed to clinical trial design, ALS remains a rapidly disabling and life-shortening condition. The non-motor neuron features of ALS, including nutritional status, energy expenditure, and metabolic imbalance, are increasingly gaining attention. Indeed, the bioenergetic failure and mitochondrial dysfunction of patients with ALS impact not only the high energy-demanding motor neurons but also organs and brain areas long considered irrelevant to the disease. As such, here we discuss how considering energy balance in ALS is reshaping research on this disease, opening the path to novel targetable opportunities for its treatment.

Hormonal fluctuations across the female reproductive lifespan lead to physiological adjustments that impact insulin sensitivity and glucose metabolism, generating unique challenges in diabetes management. Although current guidelines focus primarily on diabetes care during pregnancy, they lack tailored recommendations for addressing glycaemic variability associated with menstrual cycles, contraceptive needs, and menopause. Low rates of prepregnancy counselling, limited contraceptive guidance, and underuse of hormone replacement therapy further complicate care for women with diabetes. Here we examine these care gaps, identify unmet needs across reproductive stages, and suggest research directions to develop comprehensive, stage-specific management strategies that better support women's health and improve diabetes outcomes throughout the reproductive years.

Fasting is a recurrent daily energy stress that benefits healthspan and lifespan. While ketones fuel fasting in vertebrates, the underlying transcriptional mechanism remains incompletely understood. Recently, Korenfeld et al. revealed peroxisome proliferator-activated receptor alpha (PPARα)-dependent enhancer priming as a keystone for ketone production, increasing our understanding of mechanisms underlying metabolic benefits of alternate-day fasting (ADF).

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.

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. This review focuses on the endocrine-disrupting impact of PFASs, particularly on fertility, thyroid, and metabolic functions. We highlight the complexity of the PFAS issue, given the large number of molecules and their extremely diverse mixed effects.

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. Finally, we provide an update on potential ways to manipulate astrocyte function, including genetic targeting, optogenetic and chemogenetic techniques, transplantation, and tailored exosome-based therapies, which may lead to improved treatments for metabolic disease.

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. Challenges and opportunities in lipoprotein biology with respect to inherited diseases and viral infections are also discussed. Further characterization of the biogenesis and transport of TRLs will advance both basic research in lipid biology and translational medicine for metabolic diseases.

Mitochondria perform essential metabolic processes that sustain cellular bioenergetics and biosynthesis. In a recent article, Ryu et al. explored how mitochondria coordinate biochemical reactions with opposing redox demands within the same cell. They demonstrate that subcellular mitochondrial heterogeneity enables metabolic compartmentalization to permit concurrent oxidative ATP production and reductive proline biosynthesis.

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. With limitations to currently available CVD therapeutics and no US Food and Drug Administration (FDA)-approved treatment for MASLD, this review summarizes the current understanding of VLDL metabolism that sheds light on novel therapeutic avenues to pursue for cardiometabolic disorders.