O. Revenko¹*, N. Zaichko², J. Wallace³, O. Zayachkivska¹

¹Department of Physiology, Danylo Halytskyy Lviv National Medical University, Ukraine;
²Department of Biochemistry and General Chemistry,
National Pirogov Memorial Medical University, Vinnytsia, Ukraine;
³Department of Physiology and Pharmacology, University of Calgary, Canada;
*e-mail: wersus35@gmail.com

Received: 30 December 2019; Accepted: 27 March 2020

Remodeling of adipocytes in mesentery (AM) associated with nutritional overload from high fructose diet (HFD) is a source of several comorbidities. However, its pathogenesis is still unclear and there are no specific effective drugs for AM remodeling. Recently hydrogen sulfide (H₂S) demonstrated potent cytoprotective actions. The purpose of this study was to investigate the effects and underlying mechanisms of AM remodeling in rats fed HFD and with H₂S pre-treatment. Adult male rats on standard diet (SD, control group) or HFD that underwent acute water-immersion restraint stress (WIS) were evaluated for subcellular AM adaptive responses by electron microscopy. The effects on AM of exogenous sodium hydrosulfide (NaHS, 5.6 mg/kg/day for 9 days) and the Н₂S-releasing aspirin (ASA) derivative (H₂S-ASA [ATB-340], 17.5 mg/kg/day) vs conventional ASA (10 mg/kg/day) vs vehicle were investigated. Serum glucose level, thiobarbituric acid reactive substances (TBARS), and activities of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) were examined biochemically using spectrophotometry. In the HFD groups, treatment with NaHS protected AM, as mesenteric microvascular endothelial and sub-endothelial structures were observed vs the vehicle-treated group that had signs of endothelial dysfunction, AM damage and dysfunctional mitochondria. The effect of H₂S-ASA was characterized by protection of AM against HFD and WIS-induced injury, with lower TBARS blood level and increased CSE and CBS activities. Carbohydrate overload for 4 weeks is sufficient to cause AM oxidative damage, mitochondrial dysfunction and endothelial changes. H₂S plays an important role in mesenteric adipocyte cellular survival against HFD-induced oxidative stress by decreasing overproduction of TBARS and mitochondrial dysfunction. The use of H₂S could lead to a novel approach for anti-obesity treatment.

Keywords: adipocytes, cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), hydrogen sulfide (H2S), mesentery, mitochondria, oxidative stress, thiobarbituric acid reactive substances (TBARS)