Trends in Endocrinology and Metabolism最新文献

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.

Despite the crucial role of the placenta in supporting pregnancy and fetal development, research into its susceptibility to environmental exposures has been limited by methodological challenges. We review diverse approaches to studying placental biology and responses to chemical exposures, and provide a comprehensive assessment of traditional and emerging methodologies. Beginning with an overview of placental biology and species differences, we evaluate in vivo and in vitro models, and discuss their strengths and limitations. We examine advances, including placental transfer models, toxicokinetic frameworks, and 3D microphysiological systems, for their potential to address current gaps. Last, we consider molecular epidemiology and high-throughput analyses as complementary strategies. Together, these tools support better experimental design and enhance our understanding of placental vulnerability to chemical exposures.

Neurons are exceptionally energy-demanding cells but have limited energy storage, relying on a constant supply of fuel and oxygen. Although glucose is the brain's main energy source, neurons reduce glycolysis under normal conditions. This surprising strategy helps to protect mitochondria by preserving nicotinamide-adenine dinucleotide (NAD⁺), a vital cofactor consumed by glycolysis. NAD⁺ is needed for sirtuin-driven mitophagy, a process that removes damaged mitochondria. By saving NAD⁺, neurons can maintain healthy, energy-efficient mitochondria. These mitochondria then use alternative fuels such as lactate and ketone bodies from astrocytes. Here, we discuss the way in which this balance between reduced glycolysis and active mitophagy supports brain function and overall metabolic health, highlighting a sophisticated system that prioritizes mitochondrial quality for long-term cognitive performance and systemic homeostasis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of the global population and spans a spectrum of liver abnormalities, including simple steatosis, inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Recent studies have identified triggering receptors expressed on myeloid cells 2 (TREM2)-expressing macrophages as key regulators of MASLD progression. TREM2 plays a pivotal role in regulating macrophage-mediated processes such as efferocytosis, inflammatory control, and fibrosis resolution. Additionally, soluble TREM2 (sTREM2) was proposed as a noninvasive biomarker for diagnosing and monitoring MASLD progression. However, the molecular mechanisms through which TREM2 influences MASLD pathogenesis remain incompletely understood. This review summarizes the current understanding of TREM2-expressing macrophages in MASLD, with the goal of illuminating future research and guiding the development of innovative therapeutic strategies targeting TREM2 signaling pathways.

Metabolic resilience is essential for organismal homeostasis under diverse external pressures, because responding and adapting to stressors requires energy and drives changes at every omic level. The goal of this paper is to synthesize recent advances in understanding the intricate interplay, especially between metabolic and transcriptomic responses, involved in addressing external perturbations. We highlight the importance of timing and sequence in immediate and long-term adjustments; furthermore, we underscore the evolutionary significance of metabolic resilience and its potential for developing innovative therapeutic interventions, making it a timely contribution to contemporary biological, biomedical, and environmental research fields.