The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity.

Objective: Obesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes.

Clinical and molecular profiling of human visceral adipose tissue reveals impairment of vascular architecture and remodeling as an early hallmark of dysfunction.

Adipose tissue dysfunction is more related to insulin resistance than body mass index itself and an alteration in adipose tissue function is thought to underlie the shift from metabolically healthy to unhealthy obesity. Herein, we performed a clustering analysis that revealed distinct visceral adipose tissue gene expression patterns in patients with obesity at distinct stages of metabolic dysregulation. We have built a cross-sectional cohort that aims at reflecting the evolution of the metabolic sequelae of obesity with the main objective to map the sequential events that play a role in adipose tissue dysfunction from the metabolically healthy (insulin-sensitive) state to several incremental degrees of metabolic dysregulation, encompassing insulin resistance establishment, pre-diabetes, and type 2 diabetes.

Circulating Dopamine Is Regulated by Dietary Glucose and Controls Glucagon-like 1 Peptide Action in White Adipose Tissue.

Dopamine directly acts in the liver and white adipose tissue (WAT) to regulate insulin signaling, glucose uptake, and catabolic activity. Given that dopamine is secreted by the gut and regulates insulin secretion in the pancreas, we aimed to determine its regulation by nutritional cues and its role in regulating glucagon-like peptide 1 (GLP-1) action in WAT. Solutions with different nutrients were administered to Wistar rats and postprandial dopamine levels showed elevations following a mixed meal and glucose intake.

Cinnamaldehyde Supplementation Reverts Endothelial Dysfunction in Rat Models of Diet-Induced Obesity: Role of NF-E2-Related Factor-2.

Cinnamaldehyde (CN) is an activator of NF-E2-related factor 2 (Nrf2), which has the potential to reduce endothelial dysfunction, oxidative stress and inflammation in metabolic disorders. Our main purpose was to evaluate the effects of CN on vascular dysfunction in metabolic syndrome rats. Normal Wistar (W) rats were divided into eight groups: (1) Wistar (W) rats; (2) W rats fed with a high-fat diet (WHFD); (3) W rats fed with a sucrose diet (WS); (4) WHFD fed with a sucrose diet (WHFDS); (5) W treated with CN (WCn); (6) WS treated with CN (WSCn); (7) WHFD treated with CN (WHFDCn); (8) WHFDS treated with CN (WHFDSCn).

Impairment of neurovascular coupling in the hippocampus due to decreased nitric oxide bioavailability supports early cognitive dysfunction in type 2 diabetic rats.

Numerous epidemiological and preclinical studies have established a strong correlation between type 2 diabetes (T2DM) and cognitive impairment and T2DM is now established as an undisputable risk factor in different forms of dementia. However, the mechanisms underlying cognitive impairment in T2DM are still not fully understood. The temporal and spatial coupling between neuronal activity and cerebral blood flow (CBF) - neurovascular coupling (NVC) - is essential for normal brain function.

WWOX inhibition by Zfra1-31 restores mitochondrial homeostasis and viability of neuronal cells exposed to high glucose.

Diabetes has been associated with an increased risk of cognitive decline and dementia. However, the mechanisms underlying this association remain unclear and no effective therapeutic interventions exist. Accumulating evidence demonstrates that mitochondrial defects are a key feature of diabetes contributing to neurodegenerative events.

Improvement of Glycaemia and Endothelial Function by a New Low-Dose Curcuminoid in an Animal Model of Type 2 Diabetes.

Curcumin has been suggested as a promising treatment for metabolic diseases, but the high doses required limit its therapeutic use. In this study, a new curcuminoid is synthesised to increase curcumin anti-inflammatory and antioxidant potential and to achieve hypoglycaemic and protective vascular effects in type 2 diabetic rats in a lower dose. In vitro, the anti-inflammatory effect was determined through the Griess reaction, and the antioxidant activity through ABTS and TBARS assays.

Methods to evaluate vascular function: a crucial approach towards predictive, preventive, and personalised medicine.

Endothelium, the gatekeeper of our blood vessels, is highly heterogeneous and a crucial physical barrier with the ability to produce vasoactive and protective mediators under physiological conditions. It regulates vascular tone, haemostasis, vascular inflammation, remodelling, and angiogenesis. Several cardio-, reno-, and cerebrovascular diseases begin with the dysfunction of endothelial cells, and more recently, COVID-19 was also associated with endothelial disease highlighting the need to monitor its function towards prevention and reduction of vascular dysfunction.

Cardiovascular Risk and Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis.

Objectives/hypothesis: It was previously suggested that patients with idiopathic sudden sensorineural hearing loss (ISSNHL) have a higher risk of cardiovascular disease. The aim of this study is to determine if ISSNHL patients have an increased cardiovascular risk by means of a systematic review and meta-analysis.

Methods: A systematic literature review was performed using PubMed, Embase, Cochrane Libraries and Web of Science.

Luteolin Improves Perivascular Adipose Tissue Profile and Vascular Dysfunction in Goto-Kakizaki Rats.

Unlabelled: We investigated the effects of luteolin on metabolism, vascular reactivity, and perivascular adipose tissue (PVAT) in nonobese type 2 diabetes mellitus animal model, Goto-Kakizaki (GK) rats.

Methods: Wistar and GK rats were divided in two groups: (1) control groups treated with vehicle; (2) groups treated with luteolin (10 mg/kg/day, for 2 months). Several metabolic parameters such as adiposity index, lipid profile, fasting glucose levels, glucose and insulin tolerance tests were determined.

Distinct Impact of Natural Sugars from Fruit Juices and Added Sugars on Caloric Intake, Body Weight, Glycaemia, Oxidative Stress and Glycation in Diabetic Rats.

Although fruit juices are a natural source of sugars, there is a controversy whether their sugar content has similar harmful effects as beverages' added-sugars. We aimed to study the role of fruit juice sugars in inducing overweight, hyperglycaemia, glycation and oxidative stress in normal and diabetic animal models. In diabetic Goto-Kakizaki (GK) rats, we compared the effects of four different fruit juices (4-weeks) with sugary solutions having a similar sugar profile and concentration.

Hypoglycaemic and Antioxidant Properties of (Jacq.) Lodd Ex Mart. Extract Are Associated with Better Vascular Function of Type 2 Diabetic Rats.

Oxidative stress is involved in the metabolic dysregulation of type 2 diabetes (DM2). (Aa) fruit pulp has been described for the treatment of several diseases, and recently we have proved that its leaves have phenolic compounds with a marked antioxidant effect. We aimed to assess whether they can improve metabolic, redox and vascular functions in DM2.

Impairment of the angiogenic process may contribute to lower success rate of root canal treatments in diabetes mellitus.

Aim: To investigate the association between root canal treatment outcome, diabetes mellitus, and alterations of the angiogenic process.

Methodology: A retrospective observational study was conducted in healthy (control group, CG) and diabetic (type II diabetes mellitus group, DG) patients after root canal treatment. The follow-up appointments were performed to clinically and radiographically observe symptoms, the healing of periapical lesions and the quality of root fillings.

Multiparticulate Systems of Ezetimibe Micellar System and Atorvastatin Solid Dispersion Efficacy of Low-Dose Ezetimibe/Atorvastatin on High-Fat Diet-Induced Hyperlipidemia and Hepatic Steatosis in Diabetic Rats.

The aim of this study was to develop multiparticulate systems with a combination of ezetimibe micellar systems and atorvastatin solid dispersions using croscarmellose as a hydrophilic vehicle and Kolliphor RH40 as a surfactant. The presence of a surfactant with low hydrophilic polymer ratios produces the rapid dissolution of ezetimibe through a drug-polymer interaction that reduces its crystallinity. The solid dispersion of atorvastatin with low proportions of croscarmellose showed drug-polymer interactions sufficient to produce the fast dissolution of atorvastatin.

Kinetics of radium-223 and its effects on survival, proliferation and DNA damage in lymph-node and bone metastatic prostate cancer cell lines.

Background: Metastatic castration-resistant prostate cancer (mCRPC) is associated with a very unfavorable prognosis. At this advanced stage of the disease, there are several therapeutic strategies approved in recent times, being one of them Radium-223 dichloride (Radium-223). However, its mechanisms of action and the process that conducts to cell death are not fully understood.

Atherosclerotic Process in Seroreverter Children and Adolescents Exposed to Fetal Antiretroviral Therapy.

Background: Human immunodeficiency virus infection is a recognized risk factor for premature atherosclerosis in children and adolescents. However, the atherosclerotic process in uninfected children exposed in utero to the virus and antiretroviral therapy is less clear.

Objective: To determine the potential cardiovascular risk associated to this in utero milieu exposition.

Omentin: A novel therapeutic approach for the treatment of endothelial dysfunction in type 2 diabetes.

Background: Perivascular adipose tissue (PVAT) locally influences the functioning of blood vessels and promotes vascular complications associated with diabetes and obesity. The aim of this work was to study the impact of omentin-1 on endothelial function and PVAT in a non-obese type 2 diabetes mellitus animal model, Goto-Kakizaki (GK) rats with or without high fat diet.

Material And Methods: Diabetic GK rats were divided into four groups: 1) control group; 2) group treated with omentin-1; 3) group of GK rats fed a high fat diet (GKHFD) and 4) group of GKHFD treated with omentin-1.

GLP-1 improves adipose tissue glyoxalase activity and capillarization improving insulin sensitivity in type 2 diabetes.

Methylglyoxal was shown to impair adipose tissue capillarization and insulin sensitivity in obese models. We hypothesized that glyoxalase-1 (GLO-1) activity could be diminished in the adipose tissue of type 2 diabetic obese patients. Moreover, we assessed whether such activity could be increased by GLP-1-based therapies in order to improve adipose tissue capillarization and insulin sensitivity.

(Jacq.) Lodd. ex Mart. Leaves Increase SIRT1 Levels and Improve Stress Resistance.

Oxidative stress is a metabolic disorder linked with several chronic diseases, and this condition can be improved by natural antioxidants. The fruit pulp of the palm (Jacq.) Lodd.

A rat model of enhanced glycation mimics cardiac phenotypic components of human type 2 diabetes : A translational study using MRI.

Background: The success of translational research depends on how well animal models mimic the pathophysiology of the human phenotype, and on the identification of disease mechanisms such as enhanced glycation.

Methods: Here, we studied cardiac MRI and metabolic phenotypes in human type 2 diabetes (N = 106; 55 patients+51 controls) and animal models with distinct levels of fat diet and end glycation products, to model the role of these factors in the cardiac phenotype. We included four groups of rats, designed to evaluate the role of lipid load and glucotoxicity in cardiac function and to correlate these with the cardiac phenotype observed in humans.