Sexual dimorphism modulates metabolic and cognitive alterations under HFD nutrition and chronic stress exposure in mice. Correlation between spatial memory impairment and BDNF mRNA expression in hippocampus and spleen

• Published in: Neurochemistry international Vol. 160; p. 105416
• Main Authors: Prochnik, Andrés, Burgueño, Adriana L., Rubinstein, Mara R., Marcone, María P., Bianchi, María S., Gonzalez Murano, María R., Genaro, Ana M., Wald, Miriam R.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-11-2022
• Subjects: Chronic stress; Cognition; High-fat diet; Metabolism; Neurotrophins; Peripheral lymphocytes; CD; HOMA IR; BDNF; HFD; CMS; Cognition; IL-1 beta; Metabolism; NGF; NT3; VF; Chronic stress; SF; TG; IFN-gamma; 2hPG; High-fat diet; Peripheral lymphocytes; Neurotrophins
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2022.105416

The accumulated evidence suggests that lifestyle - specifically dietary habits and stress exposure - plays a detrimental role in health. The purpose of the present study was to analyze the interplay of stress, diet, and sex in metabolic and cognitive alterations.
For this purpose, one-month-old C57Bl/6J mice were fed with a standard diet or high-fat diet (HFD). After eight weeks, one subgroup of mice from each respective diet was exposed to 20 weeks of chronic mild stress (CMS), whilst the others were left undisturbed.
After 28 weeks of HFD feeding, mice from both sexes were overweight, with an increase in caloric intake and abdominal and subcutaneous fat pads. Stress exposure induced a decrease in body weight, related to a decrease in caloric efficiency in both males and females. Results indicate that males are more susceptible than the females in modulating metabolic and cognitive functions under HFD and CMS. Although both sexes demonstrated HFD-induced weight gain, fat accumulation, insulin resistance, high cholesterol, only males exposed to CMS but not females have (i) impaired glucose tolerance with higher glucose level; (ii) significant prolonged latency in Barnes test, suggesting cognitive impairment; (iii) increased IFN-gamma expression in hippocampus, suggesting greater neuroinflammatory response; (iv) poorer cognitive performance related to a decrease in hippocampal and spleen BDNF mRNA expression.
The main finding in this study is the presence of a sexual dimorphism in modulating metabolic and cognitive functions under HFD and CMS, showing males are more susceptible than females. In addition, poorer cognitive performance was related to a decrease in hippocampal BDNF mRNA expression. Interestingly, these changes were observed in the spleen as well.
•High-fat diet and/or stress led to impaired glucose metabolism and cognitive function.•Cognitive deficit under high-fat diet and/or stress were worse in males than females.•Cognitive deficit was linked to central and peripheral fall in BDNF mRNA expression.•Lymphocyte BDNF mRNA expression as possible marker of cognitive deficit in overweight.