Dwaib, Haneen;
Ajouz, Ghina;
Mougharbil, Nahed;
Obeid, Omar;
El-Yazbi, Ahmed
Abstract 11059: Sexual Dimorphism of Therapeutic Fasting in Mitigating Metabolic and Cardiovascular Dysfunction in Prediabetes: Possible Role of Adipose Dysfunction
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Media type:
E-Article
Title:
Abstract 11059: Sexual Dimorphism of Therapeutic Fasting in Mitigating Metabolic and Cardiovascular Dysfunction in Prediabetes: Possible Role of Adipose Dysfunction
Description:
<jats:p>Our previous work on non-obese prediabetic male rats showed that early cardiovascular (CV) and metabolic impairment was associated with localized perivascular adipose tissue (PVAT) dysfunction characterized by inflammation and hypoxia fueled by uncoupling protein 1 (UCP1) overexpression and hypertrophied adipocytes.Since there has been neither recommendations for pharmacological treatment for interrupting the hypoxia machinery in PVAT, nor a clear understanding of sexual dimorphism in PVAT involvement at this stage, therefore, we hypothesized that therapeutic fasting (TF) can alleviate PVAT dysfunction, metabolic and CV stress among prediabetic rats in a sex dependent manner. Male and female rats were fed ad libitum either a control or a mild hypercaloric diet (MHC) for 12 weeks, the typical protocol to induce prediabetes in male rats. To assess the role of female sex hormones 3 additional groups of females were bilaterally ovariectomized (OVX) on week 12. Afterwards, only the TF groups were subjected to daily fasting from 7.00pm-7.00am for 12 weeks with free access to water and to MHC during the light phase. Food intake, body composition, blood pressure, blood glucose profile, echocardiography, and serum lipid profile were examined regularly. At week 24 rats were catheterized for invasive hemodynamic examination, to assess baroreceptor sensitivity. After sacrifice, aortic contractility and endothelial function were assessed and molecular investigations were performed on various pools of adipose tissue.MHC feeding induced non-obese prediabetes, signs of early cardiovascular and metabolic dysfunction with PVAT impairment malfunctioning brown adipose tissue (BAT) only in male rats. Intact female rats resisted MHC-induced derangements, while OVX rats presented an obese prediabetic phenotype, with CV and metabolic impairment and PVAT dysfunction. Strikingly,TF in the presence of MHC feeding and in the absence of calorie restriction, and estrogen in the case of females, seemed to substantially correct these dysfunction in both male and OVX rats and interrupt hypoxia in PVAT and BAT in a UCP1 dependent manner. Taken together, our work suggests a novel mechanistic understanding of which TF interferes with the hypoxia machinery in PVAT</jats:p>