Endocrine Abstracts

Inflammation and dysfunction of the hypothalamus is a common feature of experimental diet-induced obesity. As in any inflammatory process, both pro- and anti-inflammatory activity is expected to take place in the hypothalamus of obese animals. Here, we test the hypothesis that consumption of a saturated fatty acid-rich diet can modulate the activity of the important immunomodulatory system of the resolvins in the hypothalamus. Swiss mice were fed for 8 or 16 weeks (w) either on a control chow (CT) containing 4% total fat, or on a high-fat diet (HF) containing 36% fat, mostly from lard. In addition, some mice were initially fed for 8 weeks on HF and then shifted to a high-fat diet containing 9.6% omega-3 oil (W3) for another 8 weeks. At 8 weeks, the hypothalamic expression of the phospholipase A2 (PLA2) was increased. However, 15-lipoxigenase (15LO) and GPR32 (resolvin D1 receptor) expression which catalyze initial steps of the resolvin synthesis and activity, were reduced. At 16 weeks, PLA2, 15LO and GRP32 were increased as compared to control. When mice were fed on W3, significant reduction of markers of inflammation in the hypothalamus was accompanied by reduction of PLA2 and 15LO expression. Finally, a direct acute intracerebroventricular injection of resolvin D1 in the hypothalamus increases the expression of the anti-inflammatory cytokine IL10 while reducing the expression of the p65 subunit of NFkB. Thus, this is the first evidence that during diet-induced inflammation of the hypothalamus the activity of the resolvin system is modulated. This modulation seems to occur in two phases, being initially suppressed and then activated. Because the resolvin system can be activated by nutrients, we believe it may be an interesting potential target for dietary approaches to tackle obesity.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.