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 (n = 6 per group) namely: vehicle-treated (p.o.), 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.

Impact statement

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.

中文翻译：

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醋酸钠抑制HDAC可纠正链脲佐菌素-烟酰胺诱导的糖尿病大鼠的心脏代谢紊乱。

糖尿病，特别是2型糖尿病，以全球流行的比例发生，并导致心血管疾病。分子研究表明，表观遗传学改变（例如组蛋白密码修饰）参与了心脏代谢异常的发展。但是，短链脂肪酸（SCFA）的组蛋白脱乙酰基酶抑制特性被认为是表观遗传调节剂。因此，假设在II型糖尿病和SCFA（醋酸盐）中心脏组蛋白脱乙酰基酶活性增加会抑制组蛋白脱乙酰基酶，伴随着雄性Wistar大鼠葡萄糖异常失调，心脏脂质沉积和组织损伤的恢复。将二十四只雄性大鼠（240-270克）分为四组（每组n  = 6），即：媒介物治疗（po），醋酸钠治疗组（200 mg / kg），糖尿病组和糖尿病+醋酸钠治疗组。在剂量为110 mg / kg的烟酰胺后，通过腹膜内注射65 mg / kg的链脲佐菌素诱导糖尿病。结果显示，糖尿病大鼠血糖异常，血清和心脏甘油三酸酯，丙二醛，丙氨酸氨基转移酶，组蛋白脱乙酰基酶，血清天冬氨酸转氨酶，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率（GSH / GSSG）降低血清和心脏高密度脂蛋白胆固醇（HDLc），以及血清GSH / GSSG。组织学分析显示糖尿病大鼠心脏纤维被破坏。然而，乙酸钠减弱了葡萄糖的失调，并改善了血清和心脏GSH / GSSG。醋酸钠归一化心脏甘油三酸酯累积，丙二醛，血清天冬氨酸转氨酶水平，并预防糖尿病大鼠心脏组织损伤。这些作用与抑制的组蛋白脱乙酰基酶活性有关。因此，乙酸钠减弱但不能使葡萄糖调节正常化。然而，它通过抑制组蛋白脱乙酰基酶的活性，改善了糖尿病大鼠的氧化应激和脂质代谢异常驱动的心血管并发症。

影响陈述

这项研究提供了证据，表明STZ-NA诱导的糖尿病与心脏甘油三酸酯的积累和组织破坏有关，并伴随着心脏HDAC活性的相应增加。但是，乙酸钠抑制糖尿病大鼠的心脏HDAC活性并使心脏甘油三酸酯和组织完整性正常化。因此，研究表明乙酸钠对糖尿病的心脏保护有益。