Trends in Endocrinology and Metabolism最新文献

Metabolic diseases, characterized by chronic low-grade inflammation, exhibit a compromised gut barrier allowing the translocation of bacteria-derived products to bloodstream and distant metabolic organs. Bacterial DNA can be detected in metabolic tissues during the onset of these diseases, highlighting its role in the development of metabolic diseases. Extracellular vesicles (EVs) are involved in the delivery of bacterial DNA to the local tissues, and its sensing by the host triggers local and system inflammation. Understanding bacterial DNA translocation and its induced inflammation is crucial in deciphering metabolic disease pathways. Here, we delve into the mechanisms dictating the interaction between host physiology and bacterial DNA, focusing on its origin and delivery, host immune responses against it, and its roles in metabolic disorders.

Endothelial cells (ECs) form the inner lining of blood vessels that is crucial for vascular function and homeostasis. They regulate vascular tone, oxidative stress, and permeability. Dysfunction leads to increased permeability, leukocyte adhesion, and thrombosis. ECs undergo metabolic changes in conditions such as wound healing, cancer, atherosclerosis, and diabetes, and can influence disease progression. We discuss recent research that has revealed diverse intracellular metabolic pathways in ECs that are tailored to their functional needs, including lipid handling, glycolysis, and fatty acid oxidation (FAO). Understanding EC metabolic signatures in health and disease will be crucial not only for basic biology but can also be exploited when designing new therapies to target EC-related functions in different vascular diseases.

The incorporation of the glymphatic clearance system in the study of brain physiology aids in the advancement of innovative diagnostic and treatment strategies for neurological disorders. Exploring the glymphatic system across (from) neurological and (to) metabolic diseases may provide a better link between obesity and neurological disorders. Recent studies indicate the role of metabolic dysfunction as a risk factor for cognitive decline and neurological disorders through the disruption of the glymphatic system. Further investigation into how metabolic dysfunction disrupts glymphatic homeostasis and the domino effects on the neurovascular landscape, including neurovascular uncoupling, cerebral blood flow disruptions, blood-brain barrier leakage, and demyelination, can provide mechanistic insights into the link between obesity and neurological disorders.

Brain insulin resistance (BIR) contributes to neurodegenerative diseases such as Alzheimer's disease (AD). Recently, Chen et al. revealed that microglial insulin signaling loss drives neuroinflammation and amyloid-β (Aβ) accumulation, promoting AD progression. These findings provide insights for the prevention and treatment of AD and cognitive disorders.

Mitochondria must sense their environment to enable cells and organisms to adapt to diverse environments and survive during stress. However, during microbial infection, an evolutionary pressure since the inception of the eukaryotic cell, these organelles are traditionally viewed as targets for microbes. In this opinion we consider the perspective that mitochondria are domesticated microbes that sense and guard their 'host' cell against pathogens. We explore potential mechanisms by which mitochondria detect intracellular pathogens and induce mitochondria-autonomous responses that activate cellular defenses.

MicroRNAs (miRNAs) are noncoding RNA molecules that regulate gene expression post-transcriptionally and influence numerous biological processes. Aberrant miRNA expression is linked to diseases such as diabetes mellitus; indeed, miRNAs regulate pancreatic islet inflammation in both type 1 (T1D) and type 2 diabetes (T2D). Traditionally, miRNA research has focused on canonical sequences and offers a two-layer view - from expression to function. However, advances in RNA sequencing have revealed miRNA variants, called isomiRs, that arise from alternative processing or modifications of canonical sequences. This introduces a three-layer view - from expression, through sequence modifications, to function. We discuss the potential link between cellular stresses and isomiR biogenesis, and how this association could improve our knowledge of islet inflammation and dysfunction.

Lipid droplets (LDs) are dynamic organelles that communicate with other cellular components to orchestrate energetic homeostasis and signal transduction. In skeletal muscle, the presence and importance of LDs have been widely studied in myofibers of both rodents and humans under physiological conditions and in metabolic disorders. However, the role of LDs in myogenic stem cells has only recently begun to be unveiled. In this review we briefly summarize the process of LD biogenesis and degradation in the most prevalent model. We then review recent knowledge on LDs in skeletal muscle and muscle stem cells. We further introduce advanced methodologies for LD imaging and mass spectrometry that have propelled our understanding of the dynamics and heterogeneity of LDs.