Kehinde S Olaniyi1, Oluwatobi A Amusa2. 1. Cardiometabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, 360101, Nigeria. Electronic address: olaniyisk@abuad.edu.ng. 2. Cardiometabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, 360101, Nigeria.
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.
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.
Authors: Kehinde S Olaniyi; Christopher O Akintayo; Adesola A Oniyide; Adams O Omoaghe; Mosunmola B Oyeleke; Adedamola A Fafure Journal: J Diabetes Metab Disord Date: 2021-10-21
Authors: Kehinde S Olaniyi; Al-Amin M Bashir; Stephanie E Areloegbe; Isaiah W Sabinari; Christopher O Akintayo; Adesola A Oniyide; Ayodeji Aturamu Journal: PLoS One Date: 2022-07-26 Impact factor: 3.752