Trends in Endocrinology and Metabolism最新文献

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.

One-carbon metabolism (1CM), comprising folate metabolism and methionine metabolism, serves as an important mechanism for cellular energy provision and the production of vital signaling molecules, including single-carbon moieties. Its regulation is instrumental in sustaining the proliferation of cancer cells and facilitating metastasis; in addition, recent research has shed light on its impact on the efficacy of T cell-mediated immunotherapy. In this review, we consolidate current insights into how 1CM affects T cell activation, differentiation, and functionality. Furthermore, we delve into the strategies for modulating 1CM in both T cells and tumor cells to enhance the efficacy of adoptively transferred T cells, overcome metabolic challenges in the tumor microenvironment (TME), and maximize the benefits of T cell-mediated immunotherapy.

Obesity is often associated with adipose tissue (AT) inflammation and immune cell infiltration. Writing recently in Cell Reports, Liao et al. investigated the mechanisms of T cell infiltration of AT using single cell (sc)RNA-sequencing (RNA-seq), transplantation studies, in vitro co-cultures, and knock-out mice. They highlighted the crucial role of C-C motif chemokine ligand 5 (CCL5)-secreting adipose stem cells (ASCs), offering insights for potential therapies.

Disentangling which of insulin hypersecretion and insulin resistance is upstream in obesity-related type 2 diabetes (T2D) is challenging. Here, we consider the dynamics of insulin secretion and action in the fetuses of mothers with diabetes. We argue that fetal insulin hypersecretion occurs first, with insulin resistance being an adaptive protective response.

Immune checkpoint blockade (ICB) is one of the leading immunotherapies, although a variable extent of resistance has been observed among patients and across cancer types. Among the efforts underway to overcome this challenge, the microbiome has emerged as a factor affecting the responsiveness and efficacy of ICB. Active research, facilitated by advances in sequencing techniques, is assessing the predominant influence of the intestinal microbiome, as well as the effects of the presence of an intratumoral microbiome. In this review, we describe recent findings from clinical trials, observational studies of human patients, and animal studies on the impact of the microbiome on the efficacy of ICB, highlighting the role of the intestinal and tumor microbiomes and the contribution of methodological advances in their study.

The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations in the hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, and fungi. In addition, the gut microbiome shows potential as a biomarker for early HCC diagnosis and for assessing the efficacy of immunotherapy in unresectable HCC. This review examines how gut microbiota dysbiosis, with varied functional profiles, contributes to HCCs of different etiologies. We discuss therapeutic strategies to modulate the gut microbiome including diets, antibiotics, probiotics, fecal microbiota transplantation, and nano-delivery systems, and underscore their potential as an adjunctive treatment modality for HCC.