Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti 360101, Nigeria.
HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin 240001, Nigeria.
Exp Biol Med (Maywood). 2020 Apr;245(7):667-676. doi: 10.1177/1535370220913847. Epub 2020 Mar 17.
Diabetes mellitus, particularly type 2 occurs at global epidemic proportions and leads to cardiovascular diseases. Molecular studies suggest the involvement of epigenetic alterations such as histone code modification in the progression of cardiometabolic disorders. However, short chain fatty acids (SCFAs) are recognized as epigenetic modulators by their histone deacetylase inhibitory property. It is therefore hypothesized that cardiac histone deacetylase activity increases in type II diabetes and SCFA, acetate, would inhibit histone deacetylase with accompanying restoration of glucose dysregulation, cardiac lipid deposition, and tissue damage in male Wistar rats. Twenty-four male rats (240–270 g) were allotted into four groups ( = 6 per group) namely: vehicle-treated (), sodium acetate-treated (200 mg/kg), diabetic, and diabetic+sodium acetate-treated groups. Diabetes was induced by intraperitoneal injection of streptozotocin 65 mg/kg after a dose of nicotinamide 110 mg/kg. The results showed that diabetic rats had, glucose dysregulation, elevated serum and cardiac triglyceride, malondialdehyde, alanine aminotransferase, histone deacetylase, serum aspartate transaminase, cardiac low density lipoprotein cholesterol (LDLc), glutathione/glutathione disulphide ratio (GSH/GSSG), reduced serum and cardiac high density lipoprotein cholesterol (HDLc), and serum GSH/GSSG. Histological analysis revealed disrupted cardiac fiber in diabetic rats. However, sodium acetate attenuated glucose dysregulation and improved serum and cardiac GSH/GSSG. Sodium acetate normalized cardiac triglyceride accumulation, malondialdehyde, serum aspartate transaminase levels and prevented cardiac tissue damage in diabetic rats. These effects were associated with suppressed histone deacetylase activity. Therefore, sodium acetate attenuated but failed to normalize glucoregulation. Nevertheless, it ameliorated oxidative stress- and lipid dysmetabolism-driven cardiovascular complications in diabetic rats by the suppression of histone deacetylase activity.
This study provides evidence that STZ-NA-induced diabetes mellitus is associated with cardiac triglyceride accumulation and tissue disruption with corresponding increase in cardiac HDAC activity. However, sodium acetate suppresses cardiac HDAC activity and normalizes cardiac triglyceride and tissue integrity in diabetic rats. Therefore, the study suggests that sodium acetate is beneficial for cardioprotection in diabetes mellitus.
糖尿病，特别是 2 型糖尿病，在全球范围内流行，并导致心血管疾病。分子研究表明，组蛋白密码修饰等表观遗传改变参与了心脏代谢紊乱的进展。然而，短链脂肪酸 (SCFAs) 因其组蛋白去乙酰化酶抑制特性而被认为是表观遗传调节剂。因此，假设 2 型糖尿病患者心脏中的组蛋白去乙酰化酶活性增加，而 SCFA 醋酸盐会抑制组蛋白去乙酰化酶，同时伴随葡萄糖失调、心脏脂质沉积和组织损伤的恢复。将 24 只雄性 Wistar 大鼠（240-270g）分为 4 组（每组 6 只）：对照组（）、醋酸钠组（200mg/kg）、糖尿病组和糖尿病+醋酸钠组。糖尿病通过腹腔注射链脲佐菌素 65mg/kg 后给予烟酰胺 110mg/kg 诱导。结果表明，糖尿病大鼠血糖失调，血清和心脏甘油三酯、丙二醛、丙氨酸氨基转移酶、组蛋白去乙酰化酶、血清天冬氨酸氨基转移酶、心脏低密度脂蛋白胆固醇（LDLc）、谷胱甘肽/谷胱甘肽二硫化物比（GSH/GSSG）升高，血清和心脏高密度脂蛋白胆固醇（HDLc）降低，血清 GSH/GSSG。组织学分析显示糖尿病大鼠的心肌纤维紊乱。然而，醋酸钠减轻了血糖失调，并改善了血清和心脏 GSH/GSSG。醋酸钠使糖尿病大鼠心脏甘油三酯堆积、丙二醛、血清天冬氨酸氨基转移酶水平正常化，并防止心脏组织损伤。这些作用与组蛋白去乙酰化酶活性抑制有关。因此，醋酸钠减轻了但未能使葡萄糖调节正常化。尽管如此，它通过抑制组蛋白去乙酰化酶活性改善了糖尿病大鼠氧化应激和脂质代谢紊乱引起的心血管并发症。
