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.

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.

Dysregulation of immune homeostasis can precipitate chronic inflammation, thus significantly contributing to the onset and progression of metabolic and cardiovascular diseases. Myeloid-derived suppressor cells (MDSCs) constitute a heterogeneous population of immature myeloid cells that are mobilized in response to biological stressors such as tissue damage and inflammation. Although MDSCs have been extensively characterized in the contexts of cancer and infectious diseases, emerging evidence highlights their pivotal roles in the pathophysiology of metabolic and cardiovascular disorders. We discuss growing evidence for the involvement of MDSCs in the progression of metabolic and cardiovascular diseases, with the aim of deepening our understanding of MDSCs in cardiometabolic physiology and identifying the necessary steps for the development of innovative MDSC-targeted therapeutic strategies.

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.

With the rising prevalence of type 2 diabetes mellitus (T2DM) and obesity, several previously under-recognised complications associated with T2DM are becoming more evident. The most common of these emerging complications are metabolic dysfunction-associated steatotic liver disease (MASLD), cancer, dementia, sarcopenia, and frailty, as well as other conditions involving the lung, heart, and intestinal tract. Likely causative factors are chronic inflammation and insulin resistance, whereas blood glucose levels appear to play a lesser role. We discuss these complications and the new approaches being developed to prevent and manage them, especially incretin-based therapies. We argue that these new interventions may work in a complementary way to other proven cardiorenal protective therapies to reduce the burden of T2DM complications.