Impaired suppression of fatty acid release by insulin is a strong predictor of reduced whole-body insulin-mediated glucose uptake and skeletal muscle insulin receptor activation.

Aim: To examine factors underlying why most, but not all, adults with obesity exhibit impaired insulin-mediated glucose uptake, we compared: (1) adipose tissue fatty acid (FA) release, (2) skeletal muscle lipid droplet (LD) characteristics, and (3) insulin signalling events, in skeletal muscle of adults with obesity with relatively high versus low insulin-mediated glucose uptake.

Methods: Seventeen adults with obesity (BMI: 36 ± 3 kg/m) completed a 2 h hyperinsulinemic-euglycemic clamp with stable isotope tracer infusions to measure glucose rate of disappearance (glucose Rd) and FA rate of appearance (FA Ra). Skeletal muscle biopsies were collected at baseline and 30 min into the insulin infusion.

A quantitative analysis of bestrophin 1 cellular localization in mouse cerebral cortex.

Aim: Calcium-activated ligand-gated chloride channels, beyond their role in maintaining anion homeostasis, modulate neuronal excitability by facilitating nonvesicular neurotransmitter release. BEST1, a key member of this family, is permeable to γ-aminobutyric acid (GABA) and glutamate. While astrocytic BEST1 is well-studied and known to regulate neurotransmitter levels, its distribution and role in other brain cell types remain unclear.

Differential production of mitochondrial reactive oxygen species between mouse (Mus musculus) and crucian carp (Carassius carassius).

Aim: In most vertebrates, oxygen deprivation and subsequent re-oxygenation are associated with mitochondrial impairment and excess production of reactive oxygen species (ROS) like hydrogen peroxide (HO). This in turn triggers a cascade of cell-damaging events in a temperature-dependent manner. The crucian carp (Carassius carassius) is one of few vertebrates that survives months without oxygen at cold temperatures and overcomes oxidative damage during re-oxygenation periods.

Calcineurin inhibitors and the renin-angiotensin-aldosterone system.

Calcineurin inhibitors (CnIs) are effective immunosuppressants with decades of accumulated experience in treating immune disorders and, most notably, solid organ transplantation. While CnIs have significantly increased graft survival and transformed the patient standard of care, their use has been overshadowed by a number of undesired side effects. For instance, CnI-associated nephrotoxicity has been reported since early studies and remains a major therapeutic concern.

High chloride induces aldosterone resistance in the distal nephron.

Aim: Increasing the dietary intake of K in the setting of a high salt intake promotes renal Na excretion even though K concurrently enhances the secretion of aldosterone, the most effective stimulus for renal Na reabsorption. Here, we questioned whether in the high salt state a mechanism exists, which attenuates the aldosterone response to prevent renal Na reabsorption after high K intake.

Methods: Mice were fed diets containing varying amounts of Na combined with KCl or KCitrate.

The effects of cannabinoids on the kidney.

Cannabinoids are a class of drugs derived from the Cannabis plant that are widely used for the treatment of various medical conditions and recreational use. Common examples include Δ-tetrahydrocannabinol (THC), cannabidiol (CBD), spice, and 2-arachidonoylglycerol (2-AG). With more than 100 cannabinoids identified, their influence on the nervous system, role in pain management, and effects due to illicit use have been extensively studied.

Getting in the zone: Metabolite transport across liver zones.

The liver has many functions including the regulation of nutrient and metabolite levels in the systemic circulation through efficient transport into and out of hepatocytes. To sustain these functions, hepatocytes display large functional heterogeneity. This heterogeneity is reflected by zonation of metabolic processes that take place in different zones of the liver lobule, where nutrient-rich blood enters the liver in the periportal zone and flows through the mid-zone prior to drainage by a central vein in the pericentral zone.

Early growth response 1 exacerbates thoracic aortic aneurysm and dissection of mice by inducing the phenotypic switching of vascular smooth muscle cell through the activation of Krüppel-like factor 5.

Aim: Vascular smooth muscle cell (VSMC) phenotypic switching has been reported to regulate vascular function and thoracic aortic aneurysm and dissection (TAAD) progression. Early growth response 1 (Egr1) is associated with the differentiation of VSMCs. However, the mechanisms through which Egr1 participates in the regulation of VSMCs and progression of TAAD remain unknown.

Enteric glial NLRP3 inflammasome contributes to gut mucosal barrier alterations in a mouse model of diet-induced obesity.

Aim: In the present study, we investigated the involvement of NLRP3 inflammasome in the intestinal epithelial barrier (IEB) changes associated with obesity, and its role in the interplay between enteric glia and intestinal epithelial cells (IECs).

Methods: Wild-type C57BL/6J and NLRP3-KO () mice were fed with high-fat diet (HFD) or standard diet for 8 weeks. Colonic IEB integrity and inflammasome activation were assessed.