Trends in Endocrinology and Metabolism最新文献

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.

Prediabetes is a highly prevalent and increasingly common condition affecting a significant proportion of the global population. The heterogeneous nature of prediabetes presents a challenge in identifying individuals who particularly benefit from lifestyle or other therapeutic interventions aiming at preventing type 2 diabetes (T2D) and associated comorbidities. The phenotypic characteristics of individuals at risk for diabetes are associated with both specific risk profiles for progression and a differential potential to facilitate prediabetes remission and reduce the risk of future T2D. This review examines the current definition and global prevalence of prediabetes and evaluates the potential of prediabetes remission to reduce the alarming increase in the global burden of T2D.

Respiratory infections and diseases pose significant challenges to society and healthcare systems, underscoring the need for preventative and therapeutic strategies. Recent research in rodent models indicates that short-chain fatty acids (SCFAs), metabolites produced by gut bacteria, may offer medicinal benefits for respiratory conditions. In this opinion, we summarize the current literature that highlights the potential of SCFAs to enhance immune balance in humans. SCFAs have demonstrated the potential to decrease the risk of primary and secondary respiratory infections, modulate allergic airway exacerbations, and improve overall epithelial pathogen defenses. Therefore, we suggest that systemic SCFA levels could be targeted to support gut and respiratory health in specific groups, such as patients in hospital, women and their offspring, children, older adults, and athletes/military personnel.

Taurine is a conditionally essential amino acid with paradoxical roles in cancer, as both tumor and immune cells rely on it for vital functions. Here, we discuss the emerging context-dependent functions of taurine and propose therapeutic strategies that leverage or inhibit its metabolism to modulate cancer progression and immunity.

Premenopausal women and endurance-trained individuals of either sex have reduced cardiovascular disease (CVD) risk. Endurance training shifts fuel selection towards fats to spare carbohydrates; interestingly, women prioritize fats as an energy resource more than men do during exercise. Relying on fats during exercise drives whole-body lipolysis and promotes lipid uptake and oxidation capacity in skeletal muscles. These metabolic adaptations during exercise result in protection against diet-induced obesity, a healthy body fat distribution, and reduced plasma triacylglycerol (TG) concentrations. Here, we analyze how sex differences and endurance training mediate changes in skeletal muscles, including exercise-induced lipolysis, lipid uptake and β-oxidation, intramuscular TG storage, and postexercise lipid metabolism, and discuss how regulating this processes affects CVD risk.

Primary aldosteronism (PA) is a common, salt-sensitive form of endocrine hypertension. Compared with essential hypertension (EH), PA is more susceptible to cardiorenal complications and metabolic risks. However, PA has a low screening rate and a poor response to mineralocorticoid receptor antagonists (MRAs). In addition to somatic ion channel mutations and epigenetic alterations, which contribute to excessive production of aldosterone, cholesterol, as a crucial precursor for aldosterone biosynthesis, may be involved in PA pathogenesis. Abnormal adrenal cholesterol uptake and steroidogenesis have been found in patients with PA. Therefore, we propose that a statin-based therapeutic strategy may be pivotal for antagonizing PA-related comorbidities by targeting cholesterol-dependent adrenal steroidogenesis.

Lipids are metabolic messengers essential for energy production, membrane structure, and signal transduction. Beyond their recognized role, lipids have emerged as metabolic rheostats of T cell responses, with distinct species differentially modulating CD8+ T cell (CTL) fate and function. Indeed, lipids can influence T cell signaling by altering their membrane composition; in addition, they can affect the differentiation path of T cells through cellular metabolism. This Review discusses the ability of lipids to shape T cell phenotypes and functions. Based on this link between lipid metabolism, metabolic fitness and immunosurveillance, we suggest that lipid could be rationally integrated in the context of immunotherapies to fine-tune fitness and function of adoptive T cell therapy (ACT) products.

Prostate cancer (PC) is a notoriously immune-cold tumor in that it often lacks substantial infiltration by antitumor immune cells, and in advanced diseases such as neuroendocrine PC, it could be devoid of immune cells. A majority of PC patients thus have, unfortunately, been unable to benefit from recent advances in immunotherapies. What causes this immunosuppressive microenvironment around PC? In this review, we discuss various genetic and epigenetic regulators intrinsic to prostate tumor cells that could have profound effects on the tumor microenvironment, thus contributing to this immune-cold status. It will be essential to target the cancer cells themselves in order to change the tumor microenvironment to harness existing and developing immunotherapies that had great success in other tumors.