Trends in Endocrinology and Metabolism最新文献

Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) are leading causes of global liver morbidity. Addressing the complex interplay of metabolic and alcohol-related factors has led to the 'MetALD' (metabolic dysfunction and alcohol-associated liver disease) concept, categorizing individuals with metabolic dysfunction who consume alcohol beyond MASLD thresholds but below ALD criteria. MetALD is associated with increased mortality and severe liver outcomes, including accelerated progression to advanced fibrosis, cancer, and cardiovascular complications. Accurate diagnosis requires precise alcohol quantification; novel biomarkers, particularly blood phosphatidylethanol, effectively address this by overcoming the frequent underreporting of ethanol intake. This review provides an overview of MetALD diagnostic and management strategies, emphasizing the need for integrated therapeutic approaches to improve patient outcomes.

Skeletal muscle exhibits remarkable metabolic plasticity, with mitochondria playing a central role in adapting to energy demands during exercise. These organelles form a dynamic and specialized system capable of remodeling to meet metabolic challenges. Recent studies demonstrate that exercise not only stimulates mitochondrial biogenesis but also engages finely tuned quality-control mechanisms to sustain energy efficiency and performance. A key adaptation is mitochondrial fuel flexibility, the capacity to switch between lipid and carbohydrate oxidation, which underlies endurance and metabolic health. Importantly, efficient lipid utilization, rather than low lipid content, explains why trained muscle can accumulate lipids while remaining insulin sensitive. Here, we review emerging insights into how exercise reprograms skeletal muscle mitochondria to optimize fuel use and highlight implications for metabolic disease.

Microbes can extensively regulate the physiological or pathological processes of host organs by secreting metabolites. Recently, Zhang et al. demonstrated that ectopic Catenibacterium mitsuokai could secrete quinolinic acid, activating the TIE2/PI3K/AKT pathway to drive hepatocellular carcinoma. These findings offer new insights into the microbial metabolite-target organ axis.

The mitochondrial unfolded protein response (UPR^mt) is a transcriptional program that alleviates mitochondrial dysfunction by facilitating the recovery of the mitochondrial network. In Caenorhabditis elegans, reproductive maturity leads to suppression of the UPR^mt, suggesting a trade-off between maintenance of stress resilience and fertility. Here, we examine emerging evidence suggesting that the reproduction-associated suppression of UPR^mt is a representative example of the physiological costs of reproduction. We focus on the germline-to-soma intertissue signaling mechanisms recently identified in C. elegans, which modulate systemic physiological responses during reproduction. These findings not only illuminate the trade-offs between stress resistance and reproductive capacity but also underscore the broader implications of intertissue communication in coordinating resource allocation.

Exercise-induced inflammation is regarded as a response to muscle damage from mechanical stress, but controlled immune signaling can be beneficial by promoting metabolic adaptation which, for example, decreases obesity and lowers the risk of diabetes. In addition to oxidative metabolism, mitochondria play a central role in initiating innate immune signaling. We review recent work that has identified the cGAS-STING-NF-κB signaling pathway, activated by the downregulation of mitochondrial proteins CHCHD4 and TRIAP1, as mediating skeletal muscle adaptation to exercise training as well as potentially promoting cellular resilience to environmental stresses. Notably, CHCHD4 haploinsufficiency prevents obesity in aging mice; therefore, this innate immune signaling pathway could be targeted to achieve some of the health benefits of exercise.

People living with type 1 diabetes have significantly increased cardiovascular risk compared with the general population. Traditional risk factors include hypertension, dyslipidaemia, and obesity. However, those with type 1 diabetes contend with treatment-induced insulin resistance and pancreatic and incretin hormone dysfunction, leading to dysglycaemia, which also impacts cardiovascular risk. Here, we highlight the underlying metabolic environment in type 1 diabetes with a focus on glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon physiology. With the emergence of incretin-based therapies such as semaglutide (a GLP-1 receptor agonist) and tirzepatide (a combined GLP-1/GIP receptor agonist) targeting these receptor pathways, there is now potential to directly target metabolic deficits to address cardiometabolic risk in a type 1 diabetes population.