Trends in Endocrinology and Metabolism最新文献

Fatty acids (FAs) are essential nutrients that play multiple roles in cellular activities. To meet cell-specific needs, cells exhibit differential uptake of FAs in diverse physiological or pathological contexts, coordinating to maintain metabolic homeostasis. Cells tightly regulate the localization and transcription of CD36 and other key proteins that transport FAs across the plasma membrane in response to different stimuli. Dysregulation of FA uptake results in diseases such as obesity, steatotic liver, heart failure, and cancer progression. Targeting FA uptake might provide potential therapeutic strategies for metabolic diseases and cancer. Here, we review recent advances in context-specific regulation of FA uptake, focusing on the regulation of CD36 in metabolic organs and other cells.

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) superfamily. Despite its identification over 20 years ago, the functions of GDF15 remain complex and not fully elucidated. Its concentration in plasma varies widely depending on the physiological and pathophysiological state of the organism. GDF15 has been described to regulate food intake and insulin sensitivity in rodents via the GDNF family receptor α-like (GFRAL) receptor, and to be elevated in pregnancy and many disease states and decreased in physically fit individuals. We discuss the latest developments in the regulation of GDF15 secretion and its diverse physiological effects, and touch upon possible GFRAL-independent effects of GDF15. In addition, we discuss the effects of proteins and peptides derived from the same precursor protein as GDF15.

Extending healthspan - the years lived in optimal health - holds transformative potential to reduce chronic diseases and healthcare costs. Dietary restriction (DR), particularly when combined with nutrient-rich diets and exercise, is among the most effective, evidence-based strategies for enhancing metabolic health and longevity. By targeting fundamental pathways, it mitigates the onset and progression of obesity, type 2 diabetes (T2D), cardiovascular disease (CVD), neurodegeneration, and cancer. This review synthesizes human data on the impact of DR and exercise on metabolic and age-related diseases, while emphasizing key biological mechanisms such as nutrient sensing, insulin sensitivity, inflammation, mitochondrial function, and gut microbiota. We also examine the emerging role of pharmacologically induced DR, focusing on glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) that partially mimic DR and present opportunities for chronic disease prevention.

Two initiatives are reshaping how we can approach and address the persistent and widely prevalent challenge of malnutrition, the leading global risk factor for morbidity and mortality. First is the focus on precision nutrition to identify inter- and intra-individual variation in our responses to diet, and its determinants. Second is the Food is Medicine (FIM) approach, an umbrella term for programs and services that link nutrition and health through the provision of food (e.g., tailored meals, produce prescriptions) and access to healthcare services. This article outlines how interventions and programs using FIM can synergize with precision nutrition approaches to make individual- or population-level tailored nutrition accessible and affordable, help to reduce the risk of metabolic diseases, and improve quality of life.

Orosomucoids (ORMs) have historically been considered as carriers involved in drug and lipid delivery. However, recent studies indicate ORM2 as a hepatokine involved in metabolic regulation. Here, we highlight the functions of ORM2 in controlling metabolic health and disease, focusing on its newly discovered regulatory mechanisms.

Non-sugar sweeteners (NSS), low- or no-calorie alternatives to sugar, are marketed for weight loss and improved blood glucose control in people with diabetes. However, their health effects remain controversial. This review provides a brief overview of sweet taste perception and summarizes experimental findings of the impact of NSS on cardiometabolic health in animal models and humans. We also review evidence suggesting that many NSS are not metabolically inert, highlighting the challenges in related human studies. Given the conflicting and unclear data on health outcomes, additional mechanistic studies, particularly in animal models, are necessary to clarify how NSS influence feeding behaviors and energy homoeostasis.

Plant-based diets emphasize higher intake of plant foods and are low in animal products. Individuals following plant-based diets have a lower risk of chronic conditions; however, the mechanisms underlying these associations are not completely understood. Omics data have opened opportunities to investigate the mechanistic effect of dietary intake on health outcomes. Here, we review omics analyses of plant-based diets in feeding and observational studies, showing that although metabolomics and proteomics identified candidate biomarkers and distinct pathways modifiable by plant-based diets, current evidence from transcriptomics and methylomics is limited. We also argue that future studies should examine how unhealthful plant-based diets are associated with a higher risk of health outcomes and integrate multiple omics data from feeding studies to provide further mechanistic insights.

Ferroptosis has been implicated in several reproductive disorders, but the underlying mechanisms remain unknown; thus, interventions targeting this pathway are lacking. Here we summarize the emerging findings on ferroptosis in reproductive biology and corresponding disorders, and highlight perspectives and challenges on future ferroptosis research with potential clinical applications.

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.