Introduction: Obesity is known to associate with chronic systemic inflammation. However, hypothalamic inflammation also occurs in response to high fat diet (HFD)-induced obesity and is proposed to participate in central insulin/leptin resistance and the perpetuation of weight gain and systemic affectation. The weight gain and central responses to HFD differ between males and females. As hypothalamic glial cells are implicated in the central inflammatory response we hypothesized that their response to free fatty acids (FFAs) differs between the sexes.
Methods: Primary astrocyte cultures from male and female Wistar rats (2 days of age) were used. Cells were treated with a mixture of palmitic and oleic acids at 1 and 2 mM or vehicle for 24 h. Nitrates and nitrites, as a marker of oxidative stress, released to the media and mRNA levels of CPT1a, glial fibrillary acidic protein (GFAP), glucose transporter (GLUT)2, IL6, IL1β, and TNFα were quantified.
Results: After 24 h of treatment CPT1α increased (P<0.001) and the amount of nitrites and nitrates released by astrocytes rose in a dose responsive manner in both sexes (P<0.0001). GFAP mRNA levels were decreased in males at a concentration of 1×, while in females a higher concentration was needed. Basal GLUT2 levels were higher in females (P<0.01), with FFA increasing them in males and having no effect in females. Basal levels of IL1β, IL6, and TNFα were higher in male cultures compared to females (P<0.0001). In response to FFAs, IL6 increased in males and females (P<0.0001). However, IL1β and TNFα only increased in male astrocytes (P<0.0001).
Conclusion: FFAs have a direct effect on astrocytes, inducing cytokine production and oxidative stress, suggesting that these glial cells participate in the response to a HFD. Moreover, astrocytes from males are more sensitive to FFAs, indicating that this might be involved in their increased sensitivity to HFD.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology