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    Adenosine and High-intensity Interval Training as Potential Therapies on Free Fatty Acids and Metabolic Factors in High-fat Diet-Induced Obesity in Male Wistar Rats
    (Iranian Association of Pharmaceutical Scientists, 2025) Eslami, Zahra; Fallah, Ayda; Eghbal Moghanlou, Abdorreza; Baydaş, Giyasettin; Sharifian, Shohreh; Mirghani, Seyed Javad
    Obesity, caused by an inequality between energy production and consumption, is characterized by lipid accumulation in adipose tissues. Currently, around 650 million adults and roughly 340 million children and adolescents (aged 5-19 years) are affected by obesity. This condition tends to be more common among women and older populations. It is imperative to develop uncomplicated therapeutic approaches to prevent obesity-related metabolic diseases in conjunction with lifestyle modifications. Forty-three rats were randomly divided into five groups: 1. normal diet (ND), 2. High-fat diet (HFD), 3. HFD + adenosine, 4. HFD + High-intensity interval training (HIIT) + adenosine, and 5. HFD + HIIT. Gene expression of CGI-58, HSL, and AMPK in subcutaneous adipose tissues and serum level of glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), free fatty acid (FFA), and lipid profile (Triglyceride (TG), Total cholesterol (TC), Low density lipoprotein (LDL), High density lipoprotein (HDL), and Very low density lipoprotein (VLDL)) were assessed. The rats were fed HFD-induced obesity for 13 weeks. Following, adenosine 0.2 mg/ml/kg and 0.4 mg/ml/kg, as well as HIIT, were administered over 12 weeks. CGI-58, HSL and AMPK gene expression showed significant expression in all groups. HFD+HIIT+adenosine, HFD+adenosine, and HFD+HIIT groups significantly increased all genes. Conversely, FFA and glucose serum levels were significantly reduced in intervention groups. Insulin had higher serum levels in ND, HFD + adenosine, and HFD+HIIT groups, and adenosine caused decreased glucose. Also, favorable effects of HIIT and adenosine on lipid profile were observed. HIIT and adenosine can affect lipid metabolism, improve insulin resistance, and increase lipolysis in adipose tissue. Furthermore, adenosine can boost the effect of HIIT on gene expression, triggering lipolysis to prevent obesity. © 2025, Iranian Association of Pharmaceutical Scientists. All rights reserved.
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    Atorvastatin and flaxseed dietary treatments improve dyslipidemia and liver injuries in a diet-induced rat model of non-alcoholic fatty liver disease
    (MASHHAD UNIV MED SCIENCES, 2025) Eslami, Zahra; Joshaghani, Hamidreza; Moghanlou, Abdorreza Eghbal; Norouzi, Alireza; Mirghani, Seyed Javad
    Objective: Non-alcoholic fatty liver disease (NAFLD) as the most common chronic liver disease is associated with metabolic disorders including dysregulated lipid and glucose metabolism. There is no approved drug treatment for NAFLD; thus, new therapies are needed. We studied the antidyslipidemic effects of atorvastatin and/or possibly hepatoprotective effects of flaxseed/ flaxseed oil in a rat model of NAFLD. Materials and Methods: Fifty-six male Wistar rats were divided randomly into seven groups: 1) control, 2) high-fructose diet (HFD), 3) HFD +atorvastatin (20 mg/kg), 4) HFD+ flaxseed (40 g/kg), 5) HFD+ flaxseed oil (40 mg/kg), 6) HFD+flaxseed (40 g/kg) + atorvastatin (20 mg/kg) and 7) HFD+flaxseed oil (40 g/kg) +atorvastatin (20 mg/kg). The interventions were done for 23 weeks, after which anthropometric indices, lipid profile, liver enzymes, fasting blood glucose, and kidney indices were analyzed. Scoring of hematoxylin-eosin-stained liver sections was used to assess the severity of NAFLD. Results: All the treatments reduced mesenteric fat mass, and the amount of fat around the liver, except in HFD+ flaxseed +atorvastatin group. The interventions improved NAFLD activity score, which considers steatosis, lobular inflammation, and hepatocyte ballooning. However, atorvastatin was most efficient in reducing inflammation and hepatocyte ballooning. While atorvastatin reduced only Gamma-glutamyltransferase (GGT) levels, flaxseed or flaxseed oil mono-and combination therapies reduced serum levels of all liver enzymes. The interventions improved the serum lipid profile and all, except atorvastatin decreased fasting blood glucose. Conclusion: Flaxseed therapies improved NAFLD-associated liver injuries and dyslipidemia, while atorvastatin mostly reduced hepatocyte ballooning and lobular inflammation.