Long-term diet-induced obesity does not lead to learning and memory impairment in adult mice

Abstract

Obesity arising from excessive dietary fat intake is a risk factor for cognitive decline, dementia and neurodegenerative diseases, including Alzheimer’s disease. Here, we studied the effect of long-term high-fat diet (HFD) (24 weeks) and return to normal diet (ND) on behavioral features, microglia and neurons in adult male C57BL/6J mice. Consequences of HFD-induced obesity and dietary changes on general health (coat appearance, presence of vibrissae), sensory and motor reflexes, learning and memory were assessed by applying a phenotypic assessment protocol, the Y maze and Morris Water Maze test. Neurons and microglia were histologically analyzed within the mediobasal hypothalamus, hippocampus and frontal motor cortex after long-term HFD and change of diet. Long periods of HFD caused general health issues (coat alterations, loss of vibrissae), but did not affect sensory and motor reflexes, emotional state, memory and learning. Long-term HFD increased the microglial response (increased Iba1 fluorescence intensity, percentage of Iba1-stained area and Iba1 gene expression) within the hypothalamus, but not in the cortex and hippocampus. In neither of these regions, neurodegeneration or intracellular lipid droplet accumulation was observed. The former alterations were reversible in mice whose diet was changed from HFD to ND. Taken together, long periods of excessive dietary fat alone do not cause learning deficits or spatial memory impairment, though HFD-induced obesity may have detrimental consequences for cognitive flexibility. Our data confirm the selective responsiveness of hypothalamic microglia to HFD.

Partial MCT1 invalidation protects against diet-induced non-alcoholic fatty liver disease and the associated brain dysfunction

“…These results are not due to changes in swimming abilities, which were not different between groups (supplementary figure 3C). No learning and memory deficits were detected in these mice (supplementary figure 3), agreeing with other animal studies 20 .…”

Plant Sterol-Poor Diet Is Associated with Pro-Inflammatory Lipid Mediators in the Murine Brain

“…Our findings support a potential role of nutrition-derived PSs for the regulation of inflammatory processes in the brain. Learning and memory were not affected by HF-induced obesity [46].…”

The Obese Brain: Mechanisms of Systemic and Local Inflammation, and Interventions to Reverse the Cognitive Deficit

“…On the other hand, there are studies in mice where memory deficits were quickly reversed by switching the animals from an HFD to a low-fat diet ( McLean et al, 2018 ). The above was seen even after prolonged exposure to HFD-feeding (24 weeks), where after returning to a regular diet, the animals did not present learning deficits or spatial memory impairment ( Leyh et al, 2021 ), suggesting that these impairments might be reversible, at least at some point.…”