Trends in Endocrinology and Metabolism最新文献

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.

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.

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. Refining our understanding of these key areas, especially from the clinical angle, may help us to better understand and attenuate aging processes and improve overall health outcomes.

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. Ultimately, this review aims to highlight the current state of knowledge regarding metformin and its related emerging discoveries, while also outlining critical future research directions.

Pancreatic islets, particularly insulin-producing β-cells, are central regulators of glucose homeostasis capable of responding to a variety of metabolic stressors. Pregnancy is a unique physiological stressor, necessitating the islets to adapt to the complex interplay of maternal and fetal-placental factors influencing the metabolic milieu. In this review we highlight studies defining gestational adaptation mechanisms within maternal islets and emerging studies revealing islet adaptations during the early postpartum and lactation periods. These include adaptations in both β and in 'non-β' islet cells. We also discuss insights into how gestational and postpartum adaptation may inform pregnancy-specific and general mechanisms of islet responses to metabolic stress and contribute to investigation of gestational diabetes.

Immune checkpoint inhibitors (ICIs) are associated with multiple endocrine side effects, including thyroid disfunctions. In addition, the efficacy and safety profiles of ICIs in the pediatric population need clarification. Here, we discuss the main evidence regarding the efficacy and thyroid toxicities of ICIs in children.

Lipedema is a poorly understood disorder of adipose tissue characterized by abnormal but symmetrical deposition of subcutaneous white adipose tissue (WAT) in proximal extremities. Here, we propose that the underlying cause for lipedema could be triggered by a selective accumulation of bacterial lipopolysaccharides (LPS; also known as endotoxin) in gluteofemoral WAT. Together with a malfunctioning complement system, this induces low-grade inflammation in the depot and raises its uncontrollable expansion. Correspondingly, more attention should be paid in future research to the endotoxemia prevalent in patients with lipedema. We would like to propose that proper management of endotoxemia can reduce the progression and even improve the state of disease in patients with lipedema.

The intestine is a proliferative tissue subjected to a variety of stresses that disturb its homeostasis. A recent study by Tucker et al. demonstrated that loss of the tumor suppressor SIRT4 leads to increased cell proliferation via the de novo nucleotide biosynthesis pathway over the salvage pathway after ionizing irradiation (IR).

In a recent article, Leeson-Payne et al. demonstrate that GPR75 knock-out in mice results in lower body fat and reduced hepatic lipid accumulation, with an increase in physical activity and energy expenditure. Loss-of-function (LoF) GPR75 variants in the UK Biobank (UKBB) are associated with reduced liver steatosis, suggesting potential therapeutic implications in metabolic dysfunction-associated steatotic liver disease (MASLD).

Selenium (Se) is an essential trace element, which is inserted as selenocysteine (Sec) into selenoproteins during biosynthesis, orchestrating their expression and activity. Se is associated with both beneficial and detrimental health effects; deficient supply or uncontrolled supplementation raises concerns. In particular, Se was associated with an increased incidence of type 2 diabetes (T2D) in a secondary analysis of a randomized controlled trial (RCT). In this review, we discuss the intricate relationship between Se and diabetes and the limitations of the available clinical and experimental studies. Recent evidence points to sexual dimorphism and an association of Se deficiency with gestational diabetes mellitus (GDM). We highlight the emerging evidence linking high Se status with improved prognosis in patients with T2D and lower risk of macrovascular complications.