Non-alcoholic fatty liver induces insulin resistance and metabolic disorders with development of brain damage and dysfunction

Abstract

In the present study we investigated the effect of the non-alcoholic fatty liver disease (NAFLD) on the alterations in the activity of neurotransmitters catabolizing enzymes and energy catabolising enzymes, prooxidants, endogenous antioxidants and proinflammatory cytokines in brain tissue of NAFLD rats. Rats were intraperitonealy injected with CCl4 solution at a dose of (0.021 mole/Kg, 20 μL, body weight) three times weekly for four weeks. Acetylcholine esterase (AChE), monoamine oxidase (MAO), prooxidant/ antioxidants status, ATPase, lipid profile and glucose level were estimated spectrophotometrically while inflammatory markers; interleukin 6 and tumor necrosis factor alpha (IL6 and TNF-α) and insulin were assessed by ELISA technique. Our results showed that the induced NAFLD and insulin resistance (IR) were accompanied with hyperglycemia and hyperlipidemia and lowered brain glucose level with elevated ATPase activity, prooxidant status (TBARS level, xanthine oxidase and cytochrome 2E1 activities), and inflammatory markers. Through the induction period AChE activity was significantly increased compared to control in blood, liver and brain tissues. Also, MAO activity was significantly increased in both brain and liver tissue but decreased in serum compared with control. These biochemical data were supported with pathophysiological analysis that showed severe neurodegeneration, pyknosis acuolations and cavitations. These observations warrant the reassessment of the conventional concept that the NAFLD with IR progression may induce disturbances in activities of neurotransmitters catabolising enzymes and energy production accompanied with oxidative stress and metabolic disorders, acting as relative risk factors for brain dysfunction and damage with the development of age-associated neurodegenerative diseases such as Alzheimer's disease.

Black rice (Oryza sativa L.) extract attenuates hepatic steatosis in C57BL/6 J mice fed a high-fat diet via fatty acid oxidation

“…These findings fit with prior evidence indicating that higher insulin levels co-exist with elevated levels of TC and TG in the progressive state of NAFLD [35], as well as studies showing that suppression of very-low-density lipoprotein secretion and fatty acid β-oxidation produces hepatic TG accumulation [5,6]. Although body weight change did not differ among the groups in our study, we did observe a significant increase in relative liver weight and hepatic steatosis accompanied by a partial mild inflammationin the HF group.…”

“…Although no significant effects of dietary BRE supplementation on insulin resistance were observed in our model, the reduced serum TG and TC levels observed in the HF + BRE1% group were associated with a reduction in hepatic steatosis relative to that seen in the HF group [35]. BRE supplementation was also associated with fewer visible steatotic livers compared with that in mice fed a high-fat diet without BRE supplementation.…”

Protective Effect of Genistein against Neuronal Degeneration in ApoE−/− Mice Fed a High-Fat Diet

“…Diet-induced insulin resistance also accelerated Aβ pathology by activating γ-secretase and inactivating insulin-degrading enzyme in the Tg2576 AD mouse model [42]. Furthermore, insulin resistance-mediated activation of neurotransmitter catabolizing enzymes, including acetylcholine esterase and monoamine oxidase, was suggested to act as a relative risk factor for brain dysfunction and damage in rats with nonalcoholic fatty liver disease [44]. ER stress has been shown to play an important role in tau phosphorylation.…”

Pathology supported genetic testing and treatment of cardiovascular disease in middle age for prevention of Alzheimer’s disease

“…NAFLD is the hepatic manifestation of MetS and is considered an independent risk factor for CVD. Ghareeb et al (2011) have demonstrated that NAFLD may induce insulin resistance and metabolic disorders associated with age-associated neurodegenerative diseases such as AD.…”