Sodium acetate-mediated inhibition of histone deacetylase alleviates hepatic lipid dysregulation and its accompanied injury in streptozotocin-nicotinamide-induced diabetic rats - 18/06/20
páginas | 10 |
Iconografías | 9 |
Vídeos | 0 |
Otros | 0 |
Graphical abstract |
Highlights |
• | STZ-NA-induced diabetes mellitus (DM) progresses to hepatic lipotoxicity/injury. |
• | DM-driven hepatic lipotoxicity is associated with increased HDAC activity. |
• | SAT reverses HDAC activity and normalizes hepatic lipid and tissue integrity in DM rats. |
• | SAT-led beneficial effects are associated with attenuated oxidative stress and proinflammation in DM rats. |
Abstract |
Objective |
Hepatic lipid dysregulation with consequent lipotoxicity remains critical in the progression of non-alcoholic fatty liver disease, a rising prevalent complication of diabetes mellitus particularly type 2 diabetes. Diabetes-associated hepatic complications are among the leading causes of liver-related morbidity and mortality worldwide. Short chain fatty acids (SCFAs) have been demonstrated to regulate glycemic metabolism but its effect on diabetes-driven hepatic perturbation is unknown. This study is therefore designed to investigate the effect of SCFAs, acetate on diabetes-characterised hepatic lipotoxicity, and plausible involvement of histone deacetylase (HDAC) activity.
Methods |
Adult male Wistar rats (230−260 g) were allotted into groups (n = 6/group) namely: control (vehicle; p.o.), sodium acetate (SAT)-treated (200 mg/kg), diabetic with/without SAT groups. Diabetes was induced by intraperitoneal injection of streptozotocin 65 mg/kg after a dose of nicotinamide 110 mg/kg.
Results |
Data from diabetic animals showed increased fasting glycemia and insulinemia, decreased insulin sensitivity and body weight with increased relative hepatic mass. It also revealed increased hepatic lipid, serum/hepatic malondialdehyde, tissue necrosis factor-α, uric acid, aspartate transaminase, alanine aminotransferase and decreased glutathione content with elevated hepatic HDAC. Histologically, the hepatic tissue was characterised with disrupted architecture, inflammation of central vein and foci of periportal and sinusoidal cellular infiltration. However, these alterations were attenuated by sodium acetate.
Conclusion |
The study demonstrates that diabetes mellitus drives hepatic lipotoxicity, characterised with lipid accumulation, excessive lipid peroxidation, pro-inflammation, depleted glutathione content and accompanied by increased HDAC activity. Besides, the study suggests that acetate ameliorates diabetes-associated hepatic lipotoxicity through HDAC suppression and enhancement of insulin sensitivity.
El texto completo de este artículo está disponible en PDF.Keywords : Acetate, Diabetes, Histone deacetylase, Lipid, Liver, Metabolism
Esquema
Vol 128
Artículo 110226- août 2020 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
El acceso al texto completo de este artículo requiere una suscripción.
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
La compra de artículos no está disponible en este momento.
¿Ya suscrito a @@106933@@ revista ?