miR-519d Overexpression Is Associated With Human Obesity

Obesity is a consequence of imbalance of food intake and energy expenditure that results in storage of energy as fat, primarily in adipose tissue. MicroRNAs are non-coding RNAs that regulate gene expression in metabolic pathways and they are also involved in fat-cell development. The aim of this study was to evaluate whether microRNA dysfunction contributes to obesity. We analyzed, by microarray, the expression profile of 1,458 microRNAs in subcutaneous adipose tissue (SAT) from nondiabetic severely obese (n = 20) and nonobese adults (n = 8). Among 42 differently expressed microRNAs, we confirmed by reverse-transcription PCR (RT-PCR) that miR-519d was overexpressed whereas the protein levels of peroxisome proliferator-activated receptor-α (PPARA) (a predicted miR 519d target) were lower, at western analysis, in severely obese vs. nonobese subjects. We also show that miR-519d specifically and dose-dependently suppressed translation of the PPARA protein, and increased lipid accumulation during preadipocyte differentiation. Because PPARA plays a central role in fatty acid homeostasis, and in the transcriptional regulation of genes that are necessary for maintenance of the redox balance during the oxidative catabolism of fatty acids, we suggest that PPARA loss and miR-519d overexpression could be associated with metabolic imbalance and subsequent adipocyte hypertrophy in SAT during obesity

Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15.

Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15) causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1). Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4) restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg ped/pea-15) by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance

Determinants of weight, psychological status, food contemplation and lifestyle changes in patients with obesity during the COVID-19 lockdown: a nationwide survey using multiple correspondence analysis

Introduction The corona virus disease 2019 (COVID-19) pandemic forced most of the Italian population into lockdown from 11 March to 18 May 2020. A nationwide survey of Italian Clinical Nutrition and Dietetic Services (Obesity Centers or OCs) was carried out to assess the impact of lockdown restrictions on the physical and mental wellbeing of patients with obesity (PWO) who had follow-up appointments postponed due to lockdown restrictions and to compare determinants of weight gain before and after the pandemic. Methods We designed a structured 77-item questionnaire covering employment status, diet, physical activity and psychological aspects, that was disseminated through follow-up calls and online between 2 May and 25 June 2020. Data were analyzed by multiple correspondence analysis (MCA) and multiple linear regression. Results A total of 1,232 PWO from 26 OCs completed the questionnaires (72% female, mean age 50.2 +/- 14.2 years; mean BMI 34.7 +/- 7.6 kg/m(2); 41% obesity class II to III). During the lockdown, 48.8% gained, 27.1% lost, while the remainder (24.1%) maintained their weight. The mean weight change was +2.3 +/- 4.8 kg (in weight gainers: +4.0 +/- 2.4 kg; +4.2% +/- 5.4%). Approximately 37% of participants experienced increased emotional difficulties, mostly fear and dissatisfaction. Sixty-one percent reduced their physical activity (PA) and 55% experienced a change in sleep quality/quantity. The lack of online contact (37.5%) with the OC during lockdown strongly correlated with weight gain (p < 0.001). Using MCA, two main clusters were identified: those with unchanged or even improved lifestyles during lockdown (Cluster 1) and those with worse lifestyles during the same time (Cluster 2). The latter includes unemployed people experiencing depression, boredom, dissatisfaction and increased food contemplation and weight gain. Within Cluster 2, homemakers reported gaining weight and experiencing anger due to home confinement. Conclusions Among Italian PWO, work status, emotional dysregulation, and lack of online communication with OCs were determinants of weight gain during the lockdown period

miR-519d Overexpression Is Associated With Human Obesity.

Obesity is a consequence of imbalance of food intake and energy expenditure that results in storage of energy as fat, primarily in adipose tissue. MicroRNAs are non-coding RNAs that regulate gene expression in metabolic pathways and they are also involved in fat-cell development. The aim of this study was to evaluate whether microRNA dysfunction contributes to obesity. We analyzed, by microarray, the expression profile of 1,458 microRNAs in subcutaneous adipose tissue (SAT) from nondiabetic severely obese (n = 20) and nonobese adults (n = 8). Among 42 differently expressed microRNAs, we confirmed by reverse-transcription PCR (RT-PCR) that miR-519d was overexpressed whereas the protein levels of peroxisome proliferator-activated receptor-alpha (PPARA) (a predicted miR 519d target) were lower, at western analysis, in severely obese vs. nonobese subjects. We also show that miR-519d specifically and dose-dependently suppressed translation of the PPARA protein, and increased lipid accumulation during preadipocyte differentiation. Because PPARA plays a central role in fatty acid homeostasis, and in the transcriptional regulation of genes that are necessary for maintenance of the redox balance during the oxidative catabolism of fatty acids, we suggest that PPARA loss and miR-519d overexpression could be associated with metabolic imbalance and subsequent adipocyte hypertrophy in SAT during obesity

miR-519d overexpression is asociated with human obesity

Obesity is a consequence of imbalance of food intake and energy expenditure that results in storage of energy as fat, primarily in adipose tissue. MicroRNAs are non-coding RNAs that regulate gene expression in metabolic pathways and they are also involved in fat-cell development. The aim of this study was to evaluate whether microRNA dysfunction contributes to obesity. We analyzed, by microarray, the expression profile of 1,458 microRNAs in subcutaneous adipose tissue (SAT) from nondiabetic severely obese (n = 20) and nonobese adults (n = 8). Among 42 differently expressed microRNAs, we confirmed by reverse-transcription PCR (RT-PCR) that miR-519d was overexpressed whereas the protein levels of peroxisome proliferator-activated receptor-α (PPARA) (a predicted miR 519d target) were lower, at western analysis, in severely obese vs. nonobese subjects. We also show that miR-519d specifically and dose-dependently suppressed translation of the PPARA protein, and increased lipid accumulation during preadipocyte differentiation. Because PPARA plays a central role in fatty acid homeostasis, and in the transcriptional regulation of genes that are necessary for maintenance of the redox balance during the oxidative catabolism of fatty acids, we suggest that PPARA loss and miR-519d overexpression could be associated with metabolic imbalance and subsequent adipocyte hypertrophy in SAT during obesity