Dataset Information

Mechanisms of obesity-induced metabolic and vascular dysfunctions.

ABSTRACT: Obesity has reached epidemic proportions and its prevalence is climbing. Obesity is characterized by hypertrophied adipocytes with a dysregulated adipokine secretion profile, increased recruitment of inflammatory cells, and impaired metabolic homeostasis that eventually results in the development of systemic insulin resistance, a phenotype of type 2 diabetes. Nitric oxide synthase (NOS) is an enzyme that converts L-arginine to nitric oxide (NO), which functions to maintain vascular and adipocyte homeostasis. Arginase is a ureohydrolase enzyme that competes with NOS for L-arginine. Arginase activity/expression is upregulated in obesity, which results in diminished bioavailability of NO, impairing both adipocyte and vascular endothelial cell function. Given the emerging role of NO in the regulation of adipocyte physiology and metabolic capacity, this review explores the interplay between arginase and NO, and their effect on the development of metabolic disorders, cardiovascular diseases, and mitochondrial dysfunction in obesity. A comprehensive understanding of the mechanisms involved in the development of obesity-induced metabolic and vascular dysfunction is necessary for the identification of more effective and tailored therapeutic avenues for their prevention and treatment.

SUBMITTER: Atawia RT

PROVIDER: S-EPMC6689231 | biostudies-other | 2019 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Mechanisms of obesity-induced metabolic and vascular dysfunctions.

Atawia Reem T RT Bunch Katharine L KL Toque Haroldo A HA Caldwell Ruth B RB Caldwell Robert W RW

Frontiers in bioscience (Landmark edition) 20190301 5

Obesity has reached epidemic proportions and its prevalence is climbing. Obesity is characterized by hypertrophied adipocytes with a dysregulated adipokine secretion profile, increased recruitment of inflammatory cells, and impaired metabolic homeostasis that eventually results in the development of systemic insulin resistance, a phenotype of type 2 diabetes. Nitric oxide synthase (NOS) is an enzyme that converts L-arginine to nitric oxide (NO), which functions to maintain vascular and adipocyte ...[more]

PMID: 30844720

Similar Datasets

Project description:AimsThe association of strictly defined metabolic healthy obese (MHO) with subclinical cardiac function was unclear. Our study aims to examine the role of MHO in subclinical cardiac dysfunction in a Chinese population.Methods and resultsThe study subjects were recruited from Danyang from 2017 to 2019. Obesity was defined by body mass index (BMI) categories (normal weight, overweight and obesity). Metabolic health was strictly defined as having neither any of the guidelines recommended metabolic syndrome components nor insulin resistance. Thus, subjects were grouped by BMI categories and metabolic health status as six groups. Preclinical systolic (global longitudinal strain [GLS]) and diastolic function were assessed by 2D speckle tracking, and transmitral and tissue Doppler imaging, respectively. The 2757 participants (mean age ± standard deviation, 52.7 ± 11.7 years) included 1613 (58.5%) women, 999 (36.2%) obese, 2080 (75.4%) metabolically unhealthy and 93 (3.4%) MHO participants. After adjustment for covariates, the trend was similar for left ventricular (LV) ejection fraction (Ptrend ≥ 0.07) but significantly worse for GLS, e' and E/e' (Ptrend ≤ 0.02) across the six groups or passing from normal weight to obese individuals irrespective of metabolic status. MHO participants had lower GLS (20.4 vs. 21.4%) and e' (9.6 vs. 10.6 cm/s) compared with controls (P < 0.0001) but had similar GLS (P = 0.47) compared with metabolically unhealthy obese (MUO). Regardless of obesity status, metabolically unhealthy participants had worse diastolic function compared with their metabolically healthy counterparts (P ≤ 0.0004). Compared with controls, MHO individuals were at higher risk of subclinical LV systolic dysfunction (OR = 3.44, 95% CI = 1.25-9.49, P = 0.02). These results were robust to sensitivity analysis.ConclusionsMHO was substantially associated with worse subclinical systolic function although early diastolic dysfunction seemed to be more accentuated in MUO.

Project description:Background and Objectives: The work was aimed to determine the chronological sequence of events triggered by a fructose-rich diet (FRD) (10% w/v in the drinking water) in normal rats. Material and Methods: Serum parameters, liver and islet markers of metabolism, inflammation and oxidative stress were determined weekly for 21 days. Results: At the end of the first week, rats fed with a FRD showed an early increase in circulating triglycerides, fat liver deposit, and enzymatic activity of liver glucokinase and glucose-6-phosphate dehydrogenase (G6P-DH). After two weeks of such a diet, liver glucose-6-phosphatase (G6Pase) activity and liver oxidative stress markers were significantly increased. Liver sterol regulatory element-binding protein 1c (SREBP1c) mRNA also increased in the second week while their target genes fatty acid synthase (FAS) and glycerol-3-phosphate dehydrogenase (GPAT) enhanced their expression at the third week. Liver and pancreatic inflammation markers also enhanced their gene expression in the last week of treatment. Whereas both control and FRD rats remained normoglycemic throughout the entire period of treatment, blood insulin levels were significantly higher in FRD animals at the third week, thereby evidencing an insulin-resistant state (higher HOMA-IR, HOMA-B and HIS indexes). Pancreatic islets isolated from rats fed with a FRD for 3 weeks also increased glucose-induced insulin secretion (8.3 and 16.7 mM). Conclusions: FRD induces asynchronous changes involving early hypertriglyceridemia together with intrahepatic lipid deposit and metabolic disturbances from week one, followed by enhanced liver oxidative stress, liver and pancreas inflammation, pancreatic β-cell dysfunction, and peripheral insulin-resistance registered at the third week. Knowledge of time-course adaptation mechanisms involved in our rat model could be helpful in developing appropriate strategies to prevent the progression from prediabetes to Type 2 diabetes (T2D) triggered by unhealthy diets.

Dataset Information

Mechanisms of obesity-induced metabolic and vascular dysfunctions.

Publications

Mechanisms of obesity-induced metabolic and vascular dysfunctions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets