Brain Metabolic Alterations in Rats Showing Depression-Like and Obesity Phenotypes

Abstract

Current data suggest an important role of brain metabolic disturbances in the pathogenesis of depression and obesity, diseases that frequently co-occur. Our aim was to determine whether there are changes in markers characterizing glucose metabolism in prenatal stress (PS; animal model of depression), in rats fed a high-fat diet (HFD), and especially in the model of depression and obesity co-occurrence. The changes in glucose-6-phosphate, glycogen, glucose transporters (GLUT1, GLUT4), glucagonlike peptide-1 receptor (GLP-1R), and mitochondrial complexes levels in the frontal cortex and/or hippocampus were observed. In the case of the coexistence of depression and obesity, the most important changes were (1) the decrease in the membrane form of GLUT4, which may suggest weaker insulin action in the frontal cortex, and (2) the diminished GLP-1R, which could cause neurodegenerative changes in the hippocampus. However, presented results suggested that HFD weakened the PS effect of uncoupling oxidative phosphorylation in the frontal cortex.

Impaired Brain Energy Metabolism: Involvement in Depression and Hypothyroidism

“…For this reason, we compared the selected metabolic parameters in the WKY rats and the control Wistar rats under basal conditions and under conditions of decreased thyroid hormone synthesis (obtained by the administration of a thyroid peroxidase inhibitor). We examined markers of glycolysis, the Krebs cycle, and oxidative phosphorylation that were selected mainly on the basis of the results of our previous studies conducted in a prenatal stress animal model of depression (Detka et al, 2015;Głombik et al, 2018Głombik et al, , 2020. Since disturbances in mitochondrial respiration were demonstrated in both depression and hypothyroidism in the present study, the expression of oxidative phosphorylation complexes and mitochondrial activity in the various stages of respiration were analyzed in mitochondrial fractions isolated from the frontal cortex and hippocampus.…”

Fibromyalgia and Depression in Women: An 1H-NMR Metabolomic Study

“…As shown in Figure 4 , subjects with severe depression have a progressively low glucose concentration. A correlation between mood disorders and glucose dysmetabolism has been demonstrated previously [ 58 ]. Glucose is the only energy source for brain cells, and the correct function of several biochemical pathways is necessary for the following healthy glucose metabolism: (i) glycolysis and mitochondrial oxidation; (ii) metabolization of glucose in the pentose cycle, to produce NADPH needed for reactive oxygen species removal; (iii) hormone glucocorticoids, insulin, and incretin control [ 59 , 60 , 61 ].…”

“…Glucose is the only energy source for brain cells, and the correct function of several biochemical pathways is necessary for the following healthy glucose metabolism: (i) glycolysis and mitochondrial oxidation; (ii) metabolization of glucose in the pentose cycle, to produce NADPH needed for reactive oxygen species removal; (iii) hormone glucocorticoids, insulin, and incretin control [ 59 , 60 , 61 ]. Recently, abnormal glucose-related metabolic markers have been found in the hippocampus and frontal cortex, both brain regions that are primarily impaired in depression conditions [ 58 ].…”

“…These metabolites are also related to energetic dysmetabolism; previous evidence proved that increased purine concentration is related to mitochondrial dysfunction, increased oxidative stress conditions ( Figure 3 ), and muscle damage [ 62 ]. Indeed, high purine concentrations can be found in FMS [ 63 ], and they are markers for severe depression, especially in females [ 58 ].…”

Untangling the effect of insulin action on brain mitochondria and metabolism

“…By contrast, in a model of diet-induced obesity, insulin levels increased in the rat frontal cortex, but insulin receptor activation was unaltered, highlighting the important role of maintaining central insulin receptor sensitivity. In this particular model, complexes IV and V of the ETC were up-regulated, whereas OXPHOS activity and maximum respiration were reduced,79 revealing the necessity of functional insulin receptor signalling for regulating overall mitochondrial respiration. STZ treatment decreases insulin content in mouse cerebral tissue, which is restored by peripheral s.c. insulin pellet implantation.…”