Trends in Endocrinology and Metabolism最新文献

Circadian rhythms are cell-intrinsic time-keeping mechanisms that allow organisms to adapt to 24-h environmental changes, ensuring coordinated physiological functions by aligning internal metabolic oscillations with external timing cues. Disruption of daily metabolic rhythms is associated with pathological events such as cancer development, yet the mechanisms by which perturbed metabolic rhythms contribute to tumorigenesis remain unclear. Herein we review how circadian clocks drive balanced rhythmic metabolism which in turn governs physiological functions of locomotor, immune, and neuroendocrine systems. Misaligned metabolic rhythms cause pathological states which further drive cancer initiation, progression, and metastasis. Restoring the balance of metabolic rhythms with chemical, hormonal, and behavioral interventions serves as a promising strategy for cancer therapy.

The neuropeptide kisspeptin activates the hypothalamic-pituitary-gonadal (HPG) axis and influences neural circuits controlling sexual behavior. Animal studies have determined its sex-specific roles in reproductive behaviors, whereas human research has linked kisspeptin to increased brain activity in regions associated with sexual and emotional processing, making it a potential treatment for disorders of sexual desire. Here I discuss the current evidence on the promise of kisspeptin as a therapy for sexual dysfunction, highlight the challenges currently hindering its application, and advocate future studies focusing on sex-specific effects and interactions within the neuroendocrine system. Understanding its broader physiological roles and improving delivery methods will be key to unlocking kisspeptin's therapeutic potential.

Youth-onset type 2 diabetes (YO-T2D) is an urgent public health challenge that demands immediate and innovative action. The devastating trajectory of this disease - from rapid β-cell decline to early complications and poor responses to medications - compels us to rethink our approach. Here, we argue that by investing in targeted research to unravel the unique mechanisms of this condition, ensuring equitable access to cutting-edge clinical trials, and building clinical care models tailored specifically for youth, we can rewrite the narrative for these at-risk youth.

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. This review explores the potential mechanisms underlying the cardioprotective benefits of metabolic surgery and GLP-1RA-based therapies and discusses recent evidence and emerging therapies in this dynamic area of research.

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.

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).

Cardiovascular disease (CVD) remains a significant global health concern, with obesity recognized as a prominent risk factor. The 'obesity paradox' (OP) suggests that obesity does not always lead to adverse outcomes, particularly in heart failure (HF). In this forum, we discuss the relevance of the OP in the current therapeutic landscape for cardiometabolic diseases.

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.