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Sex-dependent susceptibility to brain metabolic dysfunction and memory impairment in response to pre and postnatal
Azam Abedi1, Tahereh Foroutan1, Leila Mohaghegh Shalmani2
1Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Insights
Maternal high-fat diet impacts offspring brain glucose metabolism early in life. Postweaning high-fat diet exacerbates metabolic dysfunction and memory loss in adult offspring, particularly males.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Early-life nutrition significantly influences developing brain health.
- Maternal high-fat diet (HFD) is a growing concern for offspring neurodevelopment.
- Understanding sex-specific effects of diet on brain health is crucial.
Purpose of the Study:
- To investigate if maternal HFD induces glucose metabolism impairment, neuroinflammation, and memory deficits in offspring.
- To determine if postweaning diets modify these effects in a sex-dependent manner.
- To assess Alzheimer's pathology markers in offspring exposed to maternal and postweaning HFD.
Main Methods:
- Rats were fed normal chow diet (NCD) or HFD before and during pregnancy/lactation.
- Offspring were fed NCD or HFD postweaning until adulthood (PND180).
- Assessed brain glucose metabolism, inflammation, memory, insulin resistance, and Alzheimer's markers via qPCR, PET scans, and histology.
Main Results:
- Maternal HFD altered glucose metabolism markers in PND21 offspring of both sexes.
- Adult male offspring exposed to maternal and postweaning HFD showed significant peripheral and brain metabolic disturbances.
- HFD exposure led to impaired spatial memory, increased inflammation, dementia risk markers, and neuronal loss in adult offspring, with sex-dependent effects.
Conclusions:
- Maternal HFD negatively impacts early brain glucose metabolism in both male and female offspring.
- Postweaning HFD exacerbates metabolic dysfunction and memory impairment in adult offspring, with pronounced effects in males.
- Combined maternal and postweaning HFD poses significant risks for long-term brain health and cognitive function.
Abstract:
The developing brain is sensitive to the impacts of early-life nutritional intake. This study investigates whether maternal high fat diet (HFD) causes glucose metabolism impairment, neuroinflammation, and memory impairment in immature and adult offspring, and whether it may be affected by postweaning diets in a sex-dependent manner in adult offspring. After weaning, female rats were fed HFD (55.9% fat) or normal chow diet (NCD; 10% fat) for 8 weeks before mating, during pregnancy, and lactation. On postnatal day 21 (PND21), the male and female offspring of both groups were split into two new groups, and NCD or HFD feeding was maintained until PND180. On PND21 and PND180, brain glucose metabolism, inflammation, and Alzheimer's pathology-related markers were by qPCR. In adult offspring, peripheral insulin resistance parameters, spatial memory performance, and brain glucose metabolism (18F-FDG-PET scan and protein levels of IDE and GLUT3) were assessed. Histological analysis was also performed on PND21 and adult offspring. On PND21, we found that maternal HFD affected transcript levels of glucose metabolism markers in both sexes. In adult offspring, more profoundly in males, postweaning HFD in combination with maternal HFD induced peripheral and brain metabolic disturbances, impaired memory performance and elevated inflammation, dementia risk markers, and neuronal loss. Our results suggest that maternal HFD affects brain glucose metabolism in the early ages of both sexes. Postweaning HFD sex-dependently causes brain metabolic dysfunction and memory impairment in later-life offspring; effects that can be worsened in combination with maternal HFD.
