npj Metabolic Health and Disease最新文献

Certain metabolic enzymes localize to the nucleus, where they perform regulatory functions that extend far beyond canonical metabolism. Once inside, they influence chromatin organization, transcription, DNA repair, and cell cycle progression. This review summarizes recent advances that redefine metabolism as a nuclear process and reshape our understanding of metabolic regulation. It further defines the emerging hallmarks of nuclear metabolism and discusses how these insights open new avenues for cancer therapies.

Obesity remains the most common risk factor for cardiovascular disease in Western nations. While considerable effort has focused on identifying risk factors, which contribute to the increase incidence of complications and disease, an emerging concept is the existence of resilience factors, which mitigate disease. An important resilience factor gaining increased appreciation is the amount of skeletal muscle mass. In this review, we will explore how obesity increases the most-identified vascular component of metabolic vascular disease - endothelial dysfunction-how increases in muscle mass may protect vascular function in the obese population. This review advances the concept the obesity is less a disease of body mass than body composition which is reflected in the degree of negative vascular outcomes and may be of increased relevance in consideration of therapies that promote loss of muscle mass while reducing overall body size.

Sepsis is a life-threatening syndrome characterised by dysregulated immunity, inflammation and metabolic disruption. Despite improved care, it remains a major cause of morbidity and mortality, highlighting the need for improved mechanistic insight. Immunometabolism has emerged as a framework for understanding sepsis pathophysiology. Conventional prognostic tools reflect downstream organ injury but not the metabolic states of immune cells. Emerging technologies now enable high-resolution profiling of immunometabolic changes and integrating these approaches may yield metabolic biomarkers capable of tracking immune function and refining diagnostics. This review summarises current knowledge of leukocyte metabolic dysfunction in sepsis and highlights how immunometabolic profiling can inform patient monitoring and advance biomarker-driven precision medicine.

Lipedema is a chronic disease characterized by the symmetrical accumulation of adipose tissue in the lower body, primarily affecting women. Despite being recognized for over 85 years, the pathophysiology, diagnosis, and treatment of lipedema remain complex and not fully understood. This review consolidates current knowledge, emphasizing histological, genetic, and hormonal factors, alongside diagnostic and therapeutic approaches. Histological studies highlight changes such as adipocyte hypertrophy, increased fibrosis, and vascular alterations like angiogenesis. Genetic studies suggest a strong familial component, with multiple loci potentially influencing disease onset, yet the condition remains polygenic and influenced by environmental factors. Hormonal influences, particularly estrogen, play a significant role in disease pathogenesis. Diagnostic imaging techniques like dual-energy X-ray absorptiometry (DXA), ultrasound (US), and magnetic resonance imaging (MRI) provide valuable insights but are not definitive. Therapeutic strategies, including diet, weight loss, and Complex Decongestive Therapy, offer symptom management but are not curative, with liposuction considered for severe cases where conservative methods fail. The condition's complexity stems from genetic, hormonal, and environmental influences, necessitating further research to improve diagnostic and treatment strategies. Integrating genetic and hormonal insights into clinical practice could enhance patient outcomes and quality of life, highlighting the need for continued exploration and understanding of lipedema.

Alcoholic beverages have been concerned not only for gastronomic delight but also for certain impacts on health, such as obesity, diabetes, and cardiovascular diseases. In this study, we assessed the bioactive functions of 1,1-Diethoxyethane (1,1-DEE), a flavoring compound formed during the aging process of wine by flor yeast, using both cultured cell lines and a high-fat diet (HFD) mouse model. 1,1-DEE was identified in the batches of ethanol that induced oxidation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) using gel mobility shift assay and gas chromatography-mass spectrometry. PTEN was reversibly oxidized when exposed to 1,1-DEE, but 1,2-DEE did not induce PTEN oxidation. Mechanistically, 1,1-DEE treatment enhanced the production of mitochondrial reactive oxygen species, accompanying by oxidation of PTEN and subsequent activation of Akt signaling. 1,1-DEE treatment elevated Akt activation when combined with insulin, compared with insulin alone, and alleviated palmitate-induced insulin resistance in C2C12 myoblasts. Moreover, the oral administration of 1,1-DEE alleviated glucose intolerance and insulin resistance in HFD-fed mice. 1,1-DEE also mitigated HFD-induced body weight gain and hepatic dyslipidemia without reduction of food intake. Transcriptome analysis revealed significant genes involved in the improvement of insulin sensitivity and dyslipidemia. Thus, 1,1-DEE may serve as a promising therapeutic agent for the intervention of obesity, diabetes, and dyslipidemia.

Ferroptosis, iron-dependent regulated cell death, drives age-related cardiac dysfunction. This review examines aerobic exercise modulation of ferroptosis in aging cardiomyocytes via Parkin-ACSL4 axis. Parkin promotes ACSL4 ubiquitination/degradation, reducing lipid peroxidation and ROS. Exercise activates PINK1/Parkin mitophagy and hepcidin, enhancing mitochondrial resilience and iron homeostasis. Despite promising preclinical evidence, molecular mechanisms remain unclear. Aerobic exercise offers non-pharmacological cardiac protection against ferroptosis in aging.

Prediabetes can progress to type 2 diabetes (T2D), but individual risk varies widely. Few studies have rigorously characterized subgroups at the point of prediabetes (PD) onset. Using electronic health records (EHRs), we developed a machine learning approach to stratify PD and analyze T2D progression risk. We defined PD onset based on strict HbA1c criteria and excluded patients with missing follow-ups or atypical clinical events, yielding a high-fidelity cohort of 14,436 patients from an initial pool of 74,054 (2017-2023, MedStar Health). An XGBoost model using routine features, including HbA1c, BMI, blood pressure, lipids, ALT, medication history, and lifestyle factors, was trained on 2018-2020 data and tested on 2021-2022 patients, achieving an AUC of 81.6%. Risk scores enabled subtyping into high-, medium-, and low-risk groups with distinct progression trajectories. Stratification patterns remained consistent in future cohorts. This approach supports earlier, personalized intervention and diabetes risk prediction using real-world EHR data.

Type 2 diabetes is a global health burden driven by genetic and environmental factors. Continuous glucose monitoring (CGM) can effectively guide lifestyle interventions in non-diabetic. However, predefined CGM metrics fail to fully capture the dysglycemic information contained in the high-dimensional time-series CGM data. This study employed deep learning to learn dysglycemia features from CGM data associated with diabetes and derived a digital biomarker of dysglycemia, validated against traditional dysglycemic biomarkers and diabetes polygenic risk score (PRS). Output of the deep learning model, called the deep learning-score, was significantly associated with multiple existing dysglycemic biomarkers and PRS of diabetes (P = 0.007). Moreover, existing CGM metrics were not associated with prevalent diabetes after adjusting for the deep learning-score, while the deep learning-score remained significantly associated with prevalent diabetes (P < 0.001) in a regression analysis. This digital biomarker demonstrated potential for providing dynamic feedback on dysglycemia and improving long-term intervention adherence.

The neurovascular unit includes multiple cell types that communicate with each other on a second-by-second basis using traditional neurotransmitters and other signaling molecules, however the function of each cell or the mechanisms by which homeostasis is maintained are still unclear. Here, we review the important elements of the astro- and neurovascular unit and the modulators that contribute to the orchestration of functional hyperemia in health and disease.

Low birthweight is a risk factor for hypertension and chronic kidney disease. Kidneys of low birthweight babies typically have a low nephron endowment, which is permanent. Therefore, strategies to boost or rescue nephron endowment in low birthweight offspring might be expected to decrease the prevalence of these chronic conditions. We previously reported that a high-fat diet (17% protein, 43% carbohydrate, 40% fat) fed to mice before mating and until weaning boosted nephron endowment in mice by 20%. Here, we show that offspring from dams fed a normal diet during pregnancy and switched to a high-fat diet at birth had a 14% augmented nephron endowment. Additionally, transition to a high-fat diet at birth completely rescued a 20% nephron deficit induced by feeding dams a low-protein diet (8% protein, 76% carbohydrate, 16% fat) during gestation. The augmentation and rescue of nephron endowment were associated with increased maternal caloric intake on day 1, as well as increased maternal fat and reduced carbohydrate intake during the postnatal period of rapid nephrogenesis. These findings indicate that the balance between the three macronutrients in the maternal diet, both pre- and postnatally, is crucial for nephron endowment.