Linoleic acid supplementation reverses microglial response to diet induced-obesity at hypothalamic, cortical and subcortical level in mice

Obesity is a major risk factor for neuropsychiatric alterations. Fatty regimes lead to systemic and cerebral inflammation, the latest acting through lipotoxicity on hypothalamic structures controlling energy homeostasis. Since literature points to a protective effect of linoleic acid (LA) on mood disorders through the regulation of systemic inflammation, we investigated how five weeks of LA supplementation modulates emotional behaviour and microglia-related neuroinflammation. C57BL/6j mice were fed with either a high-fat (HFD) or a standard diet for 12 weeks, underwent a battery of behavioural tests and were subsequently sacrificed for immunofluorescence staining targeting microglia-specific calcium-binding proteins (IBA-1). Neuroinflammation severity was approximated in multiple hypothalamic, cortical and subcortical regions. Our results show an anxio-depressive-like effect of sustained HFD that neither was alleviated nor worsen with LA supplementation. Increased IBA-1 expression in the HFD group was substantially reversed with LA supplementation. Thus, our results suggest anti-neuroinflammatory properties of LA not restricted to hypothalamic areas, but also evident at the cortical and subcortical level. This study is therefore relevant in the frame of obesity and neuropsychiatric disorders with a neuroinflammatory basis. Further investigation may provide more information to justify dietary strategies aiming at reducing the impact of obesity associated comorbidities.