An Overview of Inter-Tissue and Inter-Kingdom Communication Mediated by Extracellular Vesicles in the Regulation of Mammalian Metabolism.

Obesity and type 2 diabetes are associated with defects of insulin action in different tissues or alterations in β-cell secretory capacity that may be triggered by environmental challenges, inadequate lifestyle choices, or an underlying genetic predisposition. In addition, recent data shows that obesity may also be caused by perturbations of the gut microbiota, which then affect metabolic function and energy homeostasis in the host. Maintenance of metabolic homeostasis in complex organisms such as mammals requires organismal-level communication, including between the different organs and the gut microbiota.

Exosomes from Short-Term High-Fat or High-Sucrose Fed Mice Induce Hepatic Steatosis through Different Pathways.

Obesity and other closely associated diseases, such as metabolic-associated fatty liver disease (MAFLD) and type 2 diabetes, give rise to a common biometric and metabolic phenotype resulting from a different etiopathogenesis. To characterize the first stages of metabolic dysfunction induced by either obesity or hepatic steatosis, we compared two animal models of short-term feeding with either high-fat (HFD) or high-sucrose (SAC) diets. Using transcriptomic, metabolic, and calorimetric analyses, we determined that a short-term HFD leads to obesity and then hepatic steatosis through lipid storage, whereas SAC increases gluconeogenesis and de novo lipogenesis, resulting in hepatic steatosis followed later by obesity.

Treatment with EV-miRNAs Alleviates Obesity-Associated Metabolic Dysfunction in Mice.

Most cells release extracellular vesicles (EVs) that can be detected circulating in blood. We and others have shown that the microRNA contents of these vesicles induce transcriptomic changes in acceptor cells, contributing to the adjustment of metabolic homeostasis in response to environmental demands. Here, we explore the potential for modulating obesity- and exercise-derived EV-microRNAs to treat the metabolic dysfunction associated with obesity in mice.

4-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity.

Amyloid deposits in pancreatic islets, mainly formed by human islet amyloid polypeptide (hIAPP) aggregation, have been associated with loss of β-cell mass and function, and are a pathological hallmark of type 2 diabetes (T2D). Treatment with chaperones has been associated with a decrease in endoplasmic reticulum stress leading to improved glucose metabolism. The aim of this work was to investigate whether the chemical chaperone 4-phenylbutyrate (PBA) prevents glucose metabolism abnormalities and amyloid deposition in obese agouti viable yellow (A) mice that overexpress hIAPP in β cells (A hIAPP mice), which exhibit overt diabetes.

BACE2 suppression in mice aggravates the adverse metabolic consequences of an obesogenic diet.

Objective: Pancreatic β-cell dysfunction is a central feature in the pathogenesis of type 2 diabetes (T2D). Accumulating evidence indicates that β-site APP-cleaving enzyme 2 (BACE2) inhibition exerts a beneficial effect on β-cells in different models of T2D. Thus, targeting BACE2 may represent a potential therapeutic strategy for the treatment of this disease.