Ellagic Acid Affects Metabolic and Transcriptomic Profiles and Attenuates Features of Metabolic Syndrome in Adult Male Rats

Abstract

Ellagic acid, a natural substance found in various fruits and nuts, was previously shown to exhibit beneficial effects towards metabolic syndrome. In this study, using a genetic rat model of metabolic syndrome, we aimed to further specify metabolic and transcriptomic responses to ellagic acid treatment. Adult male rats of the SHR-Zbtb16Lx/k.o. strain were fed a high-fat diet accompanied by daily intragastric gavage of ellagic acid (50 mg/kg body weight; high-fat diet–ellagic acid (HFD-EA) rats) or vehicle only (high-fat diet–control (HFD-CTL) rats). Morphometric and metabolic parameters, along with transcriptomic profile of liver and brown and epididymal adipose tissues, were assessed. HFD-EA rats showed higher relative weight of brown adipose tissue (BAT) and decreased weight of epididymal adipose tissue, although no change in total body weight was observed. Glucose area under the curve, serum insulin, and cholesterol levels, as well as the level of oxidative stress, were significantly lower in HFD-EA rats. The most differentially expressed transcripts reflecting the shift induced by ellagic acid were detected in BAT, showing downregulation of BAT activation markers Dio2 and Nr4a1 and upregulation of insulin-sensitizing gene Pla2g2a. Ellagic acid may provide a useful nutritional supplement to ameliorate features of metabolic syndrome, possibly by suppressing oxidative stress and its effects on brown adipose tissue.

Influences of Microwave-Assisted Extraction Parameters on Antioxidant Activity of the Extract from Akebia trifoliata Peels

“…Moreover, rutin could be a neuroprotective agent, which improved the glutamate metabolism of brains in rats and prevented glutamate excitotoxicity [ 33 ]. In addition, ellagic acid could ameliorate features of metabolic syndrome [ 34 ]. Furthermore, ellagic acid could decrease the risk of diabetes mellitus by reducing oxidative stress, alleviating inflammation and improving insulin resistance [ 35 ].…”

Caryopteris odorata and its metabolite coumarin attenuate characteristic features of cardiometabolic syndrome in high-refined carbohydrate-high fat-cholesterol-loaded feed-fed diet rats

“…A HRCHFC diet administered to animals causes oxidative stress which is either enzymatically or non-enzymatically reflected as higher level of TBARS or reduced levels of SOD, CAT, GPx, GSTs, and GSH ( Aziz et al, 2013 ). Earlier studies reported that increased oxidative stress in HRCHFC-fed rats is usually an outcome of inflammation, insulin resistance, hypertension, dysregulated adipocytokines, and NASH ( Kabelova et al, 2021 ). Oxidative stress develops with increased ROS and reduced antioxidant enzymes, resulting in excessive molecular oxygen and hydrogen peroxide that lead to initiate lipid peroxidation ( Sharma et al, 2012 ).…”

Antiretroviral Therapy-Induced Dysregulation of Gene Expression and Lipid Metabolism in HIV+ Patients: Beneficial Role of Antioxidant Phytochemicals

“…When metabolized by the intestinal microbiota, this phytochemical forms urolithins A, B, C, or D, whose study is interesting as modulators of OS and its anti-inflammatory properties, mostly [ 164 ]. The sources are nuts and some seeds in food, but it is mainly found in fruits at high concentrations, including blackberries, raspberries, cherries, and the red pomegranate [ 165 , 166 ]. In recent years, ellagic acid’s role in MetS, diabetes, obesity, and cardiovascular conditions, including hypertension, atherosclerosis, and endothelial dysfunction, has been investigated, alongside its properties in reducing OS, enhancing lipid profile and cholesterol metabolism, decreasing inflammatory processes, and improving insulin secretion and glucose uptake [ 167 , 168 ].…”