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High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O 2 ) consumption related to ATP production, with no changes in H 2 O 2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD+L-NAME rats, with no alterations in other morphologyrelated proteins. Consistently, HFD+L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H 2 O 2 production. Calcium uptake rate and retention capacity in the neocortex of HFD+L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning and memory, whereas neocortical function remains unaffected. HighlightsA two-hit protocol using HFD+L-NAME induces metabolic dysfunction in rats Spatial memory is impacted in HFD+L-NAME rats Hippocampal but not neocortex bioenergetics is affected in HFD+L-NAME rats OPA-1 expression is upregulated in the hippocampus of HFD+L-NAME rats Cortical calcium dynamics was not affected by HFD+L-NAME
High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O 2 ) consumption related to ATP production, with no changes in H 2 O 2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD+L-NAME rats, with no alterations in other morphologyrelated proteins. Consistently, HFD+L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H 2 O 2 production. Calcium uptake rate and retention capacity in the neocortex of HFD+L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning and memory, whereas neocortical function remains unaffected. HighlightsA two-hit protocol using HFD+L-NAME induces metabolic dysfunction in rats Spatial memory is impacted in HFD+L-NAME rats Hippocampal but not neocortex bioenergetics is affected in HFD+L-NAME rats OPA-1 expression is upregulated in the hippocampus of HFD+L-NAME rats Cortical calcium dynamics was not affected by HFD+L-NAME
High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD+L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD+L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD+L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning and memory, whereas neocortical function remains unaffected.
The development of adaptive response to cold exposure is associated with the increased synthesis of the adrenal hormones involved in regulation of the immunocompetent cells’ functional and metabolic activity. Even people residing permanently in the North show different variants of response to cold. The study was aimed to determine the relationship between the baseline cortisol and adrenaline levels, as well as the changes in their concentrations associated with the adaptive immune response to whole body cooling. A total of 173 individuals were assessed before and after the short-term whole body cooling. White blood cell differential, cortisol, adrenaline and ferritin levels, and the presence of glycogen in lymphocytes were determined in peripheral blood. Three variants of response were defined: 1) the relatively low baseline levels of cortisol and adrenaline together with no increase in these levels after the cold exposure have no significant effect on the lymphocyte migration activity; 2) predominant activation of the sympathetic–adrenal–medullary axis is associated with lymphocyte mobilization into the bloodstream along with the decrease in their glycolytic activity; 3) the higher baseline levels of cortisol and further increase in its concentration until it reaches the upper limit of the normal range following cooling are associated with intensification of glycolisis in lymphocytes and the increase of lymphocyte migration to the tissues.
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