Impaired learning and memory in rats induced by a high‐fat diet: Involvement with the imbalance of nesfatin‐1 abundance and copine 6 expression

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, resulting not only in liver dysfunction, glucose and lipid metabolism disorder, but also in neuropsychiatric damage. In the present study, a NAFLD rat model was established via feeding of a high-fat diet, and behaviour was observed via the open field test (OFT), the sucrose preference test (SPT), the elevated plus maze (EPM), the forced swimming test (FST) and the Morris water maze (MWM). The plasma concentrations of alanine aminotransferase (ALT), glucose, free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique. The plasma levels of nesfatin-1, leptin and insulin were measured via enzyme-linked immunosorbent assay, and the protein expressions of p-glycogen synthase kinase-3β (GSK-3β), GSK-3β, p-β-catenin, β-catenin, cyclinD and copine 6 in the hippocampus and prefrontal cortex (PFC) were detected using western blotting. After 4 consecutive weeks of feeding with a high-fat diet, the rats showed obesity; increased plasma concentrations of ALT, glucose, FFA, TC, TG, HDL-C and LDL-C; decreased plasma levels of leptin and insulin; and inflammation and mild hepatocyte steatosis in the liver. Although there was no significant difference between groups with regard to performance in the OFT, EPM or FST, the NAFLD rats showed a decreased sucrose preference index in the SPT and impaired learning and memory in the MWM task. Moreover, the present study provides the first evidence of an increased plasma nesfatin-1 concentration in NAFLD rats, which was significantly correlated with plasma lipid concentrations and behavioural performance. Furthermore, copine 6 and p-β-catenin protein expression decreased and p-GSK-3β increased in the hippocampus and PFC of NAFLD rats. These results suggest that consuming of a high-fat diet for 4 consecutive weeks could successfully induce a NAFLD rat model. More importantly, these results provide the first evidence that impaired learning and memory in NAFLD rats was, at least partly, associated with increased plasma nesfatin-1 concentration and decreased copine 6 expression in the hippocampus and PFC.

Feed restriction since lactation has reduced anxiety in adult Wistar rats

“…Despite the animals in groups P and especially those in group G showing less weight gain after 72 or 182 days treatment, the behavior in EPM was similar to animals in groups C, GL and L. These data match those in the literature when animals were treated with a diet rich in sucrose [5,6], rich in protein [20] and rich in lipids [7,9,10,16] and also showed no change when tested in the EPM. However, the diet rich in lipids had an anxiolytic [13] and anxiogenic effect [11,12,14,15,17].…”

“…The assessment of anxiety in animals treated with obesogenic diets (rich in carbohydrates [5,6], lipids [7][8][9][10][11][12][13][14][15][16][17] and carbohydrates and lipids [18,19]) is controversial. For some authors, the diet did not change the behavior in the EPM [5][6][7]9,10,16,20], for others it increased [8,11,12,14,15,[17][18][19] or reduced anxiety [13].…”

Nesfatin-1 and caspase-cleaved cytokeratin-18: Promising biomarkers for Alzheimer’s disease?

“…It is also known that nesfatin-1 is widely expressed in these anatomical structures in the brain (20). In a previous study ,Chen et al suggested that nesfatin-1 has a moderating effect on learning and memory in rats (21) and from this point of view, higher serum levels of nesfatin-1 in Alzheimer's patients may be associated with this effect.…”

Relationship between Insulin Levels and Nonpsychotic Dementia: A Systematic Review and Meta-Analysis

“…Insulin is an active substance with a variety of biological functions that affect growth and apoptosis in neurons by participating in blood glucose metabolism [ 3 – 8 ]. The discovery of insulin in the brain suggested that insulin not only participates in metabolism and growth but is also involved in higher cognitive functions, such as learning and memory [ 3 – 5 ].…”

“…Insulin is an active substance with a variety of biological functions that affect growth and apoptosis in neurons by participating in blood glucose metabolism [ 3 – 8 ]. The discovery of insulin in the brain suggested that insulin not only participates in metabolism and growth but is also involved in higher cognitive functions, such as learning and memory [ 3 – 5 ]. Insulin has been shown to increase the expression of amyloid precursor protein (APP), beta-amyloid 42 (A β 42), and hyperphosphorylated tau in the hippocampus and frontal cortex in rats [ 6 , 9 ].…”