Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring

Autor: Wilfred C. de Vega, Aya Sasaki, Sanoji Wijenayake, Christine M. W. Lum, Patrick O. McGowan, Mouly F. Rahman
Rok vydání: 2020
Předmět:
Lipopolysaccharides
Male
0301 basic medicine
Lipopolysaccharide
Saturated fat
lcsh:RC346-429
Basal (phylogenetics)
chemistry.chemical_compound
0302 clinical medicine
Glucocorticoid receptor
Neuroinflammation
Pregnancy
Corticosterone
Lactation
Receptor
0303 health sciences
Sex Characteristics
General Neuroscience
medicine.anatomical_structure
Neurology
Prenatal Exposure Delayed Effects
lipids (amino acids
peptides
and proteins)
Female
medicine.symptom
Inflammation Mediators
Maternal high-fat diet
hormones
hormone substitutes
and hormone antagonists
Glucocorticoid
Signal Transduction
medicine.drug
medicine.medical_specialty
Offspring
Immunology
Inflammation
Glucocorticoid signaling
Biology
Diet
High-Fat
Transcript response
03 medical and health sciences
Cellular and Molecular Neuroscience
Immune system
Maternal obesity
Internal medicine
medicine
Animals
Rats
Long-Evans
Glucocorticoids
lcsh:Neurology. Diseases of the nervous system
030304 developmental biology
Research
Rats
030104 developmental biology
Endocrinology
chemistry
030217 neurology & neurosurgery
Zdroj: Journal of Neuroinflammation
Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-16 (2020)
ISSN: 1742-2094
DOI: 10.1186/s12974-020-01798-1
Popis: BackgroundMaternal obesity as a result of high levels of saturated fat (HFD) consumption leads to significant negative health outcomes in both mother and exposed offspring. Offspring exposed to maternal HFD show sex-specific alterations in metabolic, behavioral, and endocrine function, as well as increased levels of basal neuroinflammation that persists into adulthood. There is evidence that psychosocial stress or exogenous administration of corticosterone (CORT) potentiate inflammatory gene expression; however, the response to acute CORT or immune challenge in adult offspring exposed to maternal HFD during perinatal life is unknown. We hypothesize that adult rat offspring exposed to maternal HFD would show enhanced pro-inflammatory gene expression in response to acute administration of CORT and lipopolysaccharide (LPS) compared to control animals, as a result of elevated basal pro-inflammatory gene expression. To test this, we examined the effects of acute CORT and/or LPS exposure on pro and anti-inflammatory neural gene expression in adult offspring (male and female) with perinatal exposure to a HFD or a control house-chow diet (CHD).MethodsRat dams consumed HFD or CHD for four weeks prior to mating, during gestation, and throughout lactation. All male and female offspring were weaned on to CHD. In adulthood, offspring were ‘challenged’ with administration of exogenous CORT and/or LPS, and quantitative PCR was used to measure transcript abundance of glucocorticoid receptors and downstream inflammatory markers in the amygdala, hippocampus, and prefrontal cortex.ResultsIn response to CORT alone, male HFD offspring showed increased levels of anti-inflammatory transcripts, whereas in response to LPS alone, female HFD offspring showed increased levels of pro-inflammatory transcripts. In addition, male HFD offspring showed greater pro-inflammatory gene expression and female HFD offspring exhibited increased anti-inflammatory gene expression in response to simultaneous CORT and LPS administration.ConclusionsThese findings suggest that exposure to maternal HFD leads to sex-specific changes that may alter inflammatory responses in the brain, possibly as an adaptive response to basal neuroinflammation.
Databáze: OpenAIRE
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