Resveratrol and Dulaglutide ameliorate adiposity and liver dysfunction in rats with diet-induced metabolic syndrome: Role of SIRT-1 / adipokines / PPARγ and IGF-1.

BACKGROUND: Adiposity and non-alcoholic fatty liver disease (NAFLD) are common characteristics of metabolic syndrome (MS). Understanding the underlying pathogenesis is crucial for the development of new remedies. Resveratrol controls obesity and glycemic disorders in patients with MS. OBJECTIVES: This study aimed to evaluate the effect of resveratrol and dulaglutide on adipose tissues and liver in rats with MS, declaring their possible mechanisms. METHODS: Rats allocated as Control, MS (induced by a high fat/ high sucrose diet for eight weeks), MS + Resveratrol (30 mg/kg/day orally), and MS + Dulaglutide (0.6 mg/kg twice weekly SC); drugs administration was in the last four weeks. Serum biochemical measurements were done. Liver and visceral fat were processed for biochemistry, histopathology, and immunohistochemistry. RESULTS: MS results demonstrated significantly increased systolic and diastolic blood pressure, anthropometric measurements, serum levels of alanine aminotransferase (ALT), glycemic indices, and lipids with decreased HDL-C. Tissue levels of leptin, malondialdehyde (MDA), and TNF-α reactivity significantly increased. Expression of adiponectin, PPARγ, and insulin growth factor-1 (IGF-1) decreased. Also, Western blotting mRNA gene expression of liver SIRT-1 was down-regulated. Resveratrol and dulaglutide significantly and effectively reversed MS complexity, ameliorating all findings, particularly NAFLD and adiposity-induced inflammation. Resveratrol significantly appears superior to dulaglutide regarding the effects on hemodynamics, lipids, adipokines, IGF-1 levels, and adipocyte size. Parallel, dulaglutide has more influence on glycemic control. CONCLUSION: Protective effects of the drugs may be through correlations between SIRT-1/adipokines/IGF-1 and PPARγ, improving the cross-talk between insulin resistance, obesity markers, liver dysfunction, and TNF-α. Promising multi-beneficial therapies of resveratrol or dulaglutide in MS are recommended clinically for this purpose. Showing the Experimental Design.

Protective effects of melatonin and glucagon-like peptide-1 receptor agonist (liraglutide) on gastric ischaemia-reperfusion injury in high-fat/sucrose-fed rats.

Ischaemia-reperfusion (I-R) injury is a serious pathology that is often encountered with thrombotic events, during surgery when blood vessels are cross-clamped, and in organs for transplantation. Increased oxidative stress is the main pathology in I-R injury, as assessed in studies on the heart, kidney, and brain with little data available on gastric I-R (GI-R). Liraglutide is a GLP-1 receptor agonist that has insulinotropic and weight reducing actions, and melatonin that has been much studied as a chronotropic hormone; have also studied as being anti-oxidative stress agents. Herein, we aimed to explore the effects of liraglutide and melatonin on GI-R injury with high-fat/sucrose diet. Rats were divided into six groups; two diet-control, two melatonin- and two liraglutide-pretreated groups. All rats were subjected to 30 minutes of gastric ischaemia followed by 1 hour of reperfusion. Gastric tissues were assessed for the percentage of DNA fragmentation, myeloperoxidase activity, total oxidant status, total antioxidant capacity, oxidative stress index, BMI and histopathological examination. We showed that high-fat feeding for four weeks prior to GI-R significantly increased BMI, oxidative stress indices and decreased total antioxidant capacity, with a neutral effect on apoptosis compared to controls. Pretreatment with either melatonin (10 mg/kg per day orally) or liraglutide (25 µg/kg per day ip) reverses these effects. Furthermore, both drugs reduced weight only in HFS-fed rats. Both liraglutide and melatonin have nearly similar protective effects on gastric I-R injury through decreasing the oxidative stress and apoptosis.