Trends in Endocrinology & Metabolism最新文献

Extracellular noncoding RNAs (ncRNAs) have crucial roles in intercellular communications. The process of ncRNA secretion is highly regulated, with specific ncRNA profiles produced under different physiological and pathological circumstances. These ncRNAs are transported primarily via extracellular vesicles (EVs) from their origin cells to target cells, utilising both endocrine and paracrine pathways. The intercellular impacts of extracellular ncRNAs are essential for maintaining homeostasis and the pathogenesis of various diseases. Given the unique aspects of extracellular ncRNAs, here we propose the term ‘RNAkine’ to describe these recently identified secreted factors. We explore their roles as intercellular modulators, particularly in their ability to regulate metabolism and influence tumorigenesis, highlighting their definition and importance as a distinct class of secreted factors.

Cushing’s syndrome (CS) refers to the clinical features of prolonged pathological glucocorticoid excess. About 10–20% of individuals with CS have ectopic CS (ECS), that is, an adrenocorticotropin (ACTH)-producing tumour outside the pituitary gland. ACTH-secreting neuroendocrine neoplasia (NENs) can arise from many organs, although bronchial NEN, small cell lung cancer (SCLC), pancreatic NEN, thymic NEN, medullary thyroid cancer (MTC), and pheochromocytoma are the most common. Patients with ECS frequently present with severe hypercortisolism. The risk of life-threatening complications is high in severe cases, unless the hypercortisolism is effectively treated. A good outcome in ECS requires a methodical approach, incorporating prompt diagnosis, tumour localization, control of cortisol excess, and resection of the primary tumour when possible.

Exaggerated blood excursions of nutrients and endogenous molecules in response to food intake may have health consequences if they repeatedly exceed the capacity of homeostatic mechanisms. Here, I discuss the significance of abnormally high postprandial metabolic fluctuations, the role of some influencing factors, and suggest ways to avoid them.

Mitochondrial quality control (MQC) mechanisms are required to maintain a functional proteome, which enables mitochondria to perform a myriad of important cellular functions from oxidative phosphorylation to numerous other metabolic pathways. Mitochondrial protein homeostasis begins with the import of over 1000 nuclear-encoded mitochondrial proteins and the synthesis of 13 mitochondrial DNA-encoded proteins. A network of chaperones and proteases helps to fold new proteins and degrade unnecessary, damaged, or misfolded proteins, whereas more extensive damage can be removed by mitochondrial-derived vesicles (MDVs) or mitochondrial autophagy (mitophagy). Here, focusing on mechanisms in mammalian cells, we review the importance of mitochondrial protein import as a sentinel of mitochondrial function that activates multiple MQC mechanisms when impaired.

Mounting evidence suggests that physical exercise protects the brain against neurodegenerative disease. In a recent paper in Neuron, Kim et al. reported that the exercise-induced hormone irisin curbs amyloid-β buildup by promoting secretion of astrocyte-derived neprilysin. These findings may help explain the neuroprotection by irisin and exercise in Alzheimer’s disease.

High dietary fructose consumption is linked to multiple disease states, including cancer. Zhou and colleagues recently reported a novel mechanism where high dietary fructose levels increase acetate production by the gut microbiome increasing post-translational modification O-GlcNAcylation in liver cells, which contributes to disease progression in mouse models of hepatocellular carcinoma.

Resistance to anticancer therapy still represents one of the main obstacles to cancer treatment. Numerous components of the tumor microenvironment (TME) contribute significantly to the acquisition of drug resistance. Microenvironmental pressures arising during cancer evolution foster tumor heterogeneity (TH) and facilitate the emergence of drug-resistant clones. In particular, metabolic pressures arising in the TME may favor epigenetic adaptations supporting the acquisition of persistence features in tumor cells. Tumor-persistent cells (TPCs) are characterized by high phenotypic and metabolic plasticity, representing a noticeable advantage in chemo- and radio-resistance. Understanding the crosslink between the evolution of metabolic pressures in the TME, epigenetics, and TPC evolution is significant for developing novel therapeutic strategies specifically targeting TPC vulnerabilities to overcome drug resistance.

Knowledge is rapidly accumulating on basic roles and modulation of bone-marrow adipose tissue (BMAT). Among key modulators are physical forces on bones as exerted by gravity and exercise. Studying humans returning from space has revealed that, in addition to physical forces, local energetics within the bone marrow can play modulatory roles.

The function and phenotype of macrophages are intimately linked with pathogen detection. On sensing pathogen-derived signals and molecules, macrophages undergo a carefully orchestrated process of polarization to acquire pathogen-clearing properties. This phenotypic change must be adequately supported by metabolic reprogramming that is now known to support the acquisition of effector function, but also generates secondary metabolites with direct microbicidal activity. At the same time, bacteria themselves have adapted to both manipulate and take advantage of macrophage-specific metabolic adaptations. Here, we summarize the current knowledge on macrophage metabolism during infection, with a particular focus on understanding the ‘arms race’ between host immune cells and bacteria during immune responses.

Metabolic byproducts have conventionally been disregarded as waste products without functions. In this opinion article, we bring to light the multifaceted role of methylmalonic acid (MMA), a byproduct of the propionate metabolism pathway mostly commonly known as a clinical biomarker of vitamin B12 deficiency. MMA is normally present at low levels in the body, but increased levels can come from different sources, such as vitamin B12 deficiency, genetic mutations in enzymes related to the propionate pathway, the gut microbiota, and aggressive cancers. Here, we describe the diverse metabolic and signaling functions of MMA and discuss the consequences of increased MMA levels, such as during the aging process, for several age-related human pathologies.