Trends in Endocrinology and Metabolism最新文献

Abnormally increased hepatic gluconeogenesis is a significant contributor to hyperglycemia in the fasting state in patients with type 2 diabetes mellitus (T2DM) due to insulin resistance. Metformin, the most prescribed drug for the treatment of T2DM, is believed to exert its effect mainly by reducing hepatic gluconeogenesis. Here, we discuss how increased hepatic gluconeogenesis contributes to T2DM and we review newly revealed mechanisms underlying the attenuation of gluconeogenesis by metformin. In addition, we analyze the recent findings on new determinants involved in the regulation of gluconeogenesis, which might ultimately lead to the identification of novel and targeted treatment strategies for T2DM.

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.

Obesity has become a global pandemic that is associated with a range of metabolic disorders. Traditional treatment options, such as lifestyle modification and anti-obesity medications, often exhibit limited efficacy and can lead to long-term weight gain, especially upon discontinuation of the medication. Although bariatric surgery is effective, its accessibility is constrained, and only a small percentage of eligible patients receive this intervention. Over the past two decades, endoscopic bariatric and metabolic therapies (EBMTs) have emerged as minimally invasive and effective alternatives for managing obesity and its related comorbidities. This article reviews primary gastric and small bowel EBMTs, their mechanisms of action, key supporting literature, and the metabolic outcomes associated with each device and procedure.

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.

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.

Paternal health and exposure to adverse environments in the period prior to conception have a profound impact on future generations. Adversities such as stress, diet, and toxicants influence offspring health. Emerging evidence indicates that epigenetic mechanisms including noncoding RNA, DNA methylation, and chromatin remodelling mediate these effects. Preclinical studies have contributed to advancing mechanistic understanding in the field; however, human research is limited and primarily observational. Here, we discuss the evidence linking paternal to offspring health and advocate for further research in this area, which may ultimately inform policy and healthcare guidelines to improve paternal preconception health and offspring outcomes.

Non-sugar sweeteners (NSS), low- or no-calorie alternatives to sugar, are marketed for weight loss and improved blood glucose control in people with diabetes. However, their health effects remain controversial. This review provides a brief overview of sweet taste perception and summarizes experimental findings of the impact of NSS on cardiometabolic health in animal models and humans. We also review evidence suggesting that many NSS are not metabolically inert, highlighting the challenges in related human studies. Given the conflicting and unclear data on health outcomes, additional mechanistic studies, particularly in animal models, are necessary to clarify how NSS influence feeding behaviors and energy homoeostasis.

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.

Previously characterized as inert fat depots, adipocytes are now recognized as dynamic mediators of inflammatory tone, metabolic health, and nutrient homeostasis. As endocrine organs, specialized depots of adipose tissue engage in crosstalk between the gut, liver, pancreas, and brain to coordinate appetite, thermogenesis, and ultimately body weight. These functions are tightly linked to the inflammatory status of adipose tissue, which is in turn influenced by the health of the gut microbiome. Here, we review recent findings linking specific gut microbes and their secreted factors, including recently identified elements such as bacterial extracellular vesicles, to the functional status of adipocytes. We conclude that further study may generate novel approaches for treating obesity and metabolic disease.

Recent genetic studies have implicated an active role for intrahepatic lipid accumulation in the pathogenesis of both polycystic ovary syndrome (PCOS) and cardiovascular disease. These new insights may provide novel (non)pharmacological opportunities for the prevention and treatment of PCOS and cardiovascular disease at both the societal and clinical level.