ESPE Abstracts (2015) 84 P-2-341

Palmitic Acid Could Modify Cognitive and Behavioural Functions Through Sex Specific Activation of Hippocampal Astrocytes

Laura M Fragoa,b, Alejandra Freire-Regatilloa,b, Pilar Argente-Arizóna,b, Jesús Argentea,b & Julie A Chowena,b


aDepartment of Endocrinology, Instituto de Investigación Sanitaria Princesa (IP), Hospital Infantil Universitario Niño Jesús, Madrid, Spain; bDepartment of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain


Background: Prolonged poor dietary habits can result in hypothalamic inflammation and gliosis with more recent studies suggest that other brain areas may also be affected. Western or high fat diet intake has been associated with increased cognitive impairment and aberrant feeding behavior, with males and females being differentially affected. The hippocampus participates in both of these functions. Saturated free fatty acids can induce astrocyte inflammation and this could potentially result in adverse neurologic processes. Undoubtedly, a delicate balance between pro- and anti-inflammatory signals will determine long-term cellular homeostasis.

Objective: Our aim was to determine the effects of palmitic acid on hippocampal astrogliosis and whether these effects are sex-specific.

Method: Primary hippocampal astrocyte cultures were established from male and female rats (P2) using standard procedures. After 10 days, cell cultures were shaken overnight to eliminate microglia and oligodendrocytes. Cells were plated at a density of 15 000 cells/cm2. Twenty-four hours later, cells were treated in serum free media with palmitic acid (25 or 50 μM, 24 h). Levels of glial fibrillary acidic protein (GFAP) and pro- or anti-inflammatory factors were measured by western blotting.

Results: Palmitic acid increased GFAP levels in males (170% of control; P<0.01), but induced a decrease in female (30% of control; P<0.01). Levels of the inflammatory cytokine interleukin 6 (IL6) were also increased in males (390% over control; P<0.05) and decreased in females (70% of control; P<0.05). Levels of the pro-inflammatory intracellular signal p-IκB did not change in males or females.

Conclusion: Glial cells of the hippocampus respond to palmitic acid in a sexually dimorphic manner. As these cells were derived from prepubertal animals, the differential response could be an inherent difference between the sexes and could partially underlie the sex differences in propensity to develop some cognitive or behavioral dysfunctions.

Funding: This work was supported by Ministerio de Ciencia e Innovación (BFU2011–27492) co-funded by European FEDER Program, and Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición of the Instituto de Salud Carlos III, and Fundación de Endocrinología y Nutrición.

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