Dietary linoleic acid supplementation protects against obesity-induced microglial reactivity in mice

Abstract

We investigated whether linoleic acid (LA) supplementation could modulate emotional behavior and microglia-related neuroinflammation. For that, male mice of C57BL/6J genetic background fed either a high-fat diet (HFD) or a standard diet (STD) for 12 weeks, were treated with a vehicle or LA solution for 5 weeks before being evaluated for emotional behavior using a battery of behavioral tests. The animals were subsequently sacrificed and their brains collected and processed for immunofluorescence staining, targeting microglia-specific calcium-binding proteins (IBA-1). Neuroinflammation severity was assessed in multiple hypothalamic, cortical and subcortical brain regions. We show an anxio-depressive-like effect of sustained HFD feeding that was neither alleviated nor worsened with LA supplementation. However, increased IBA-1 expression and microgliosis in the HFD group were largely attenuated by LA supplementation. These observations demonstrate that the anti-neuroinflammatory properties of LA are not restricted to hypothalamic areas but are also evident at the cortical and subcortical levels. This study discloses that neuroinflammation plays a role in the genesis of neuropsychiatric disorders in the context of obesity, and that LA supplementation is a useful dietary strategy to alleviate the impact of obesity-related neuroinflammation.

CryoEM Structure of the human THIK-1 K2P K+Channel Reveals a Lower ‘Y-gate’ Regulated by Lipids and Anaesthetics

“…This is supported by the activatory effect of this lipid and of mutations within this binding pocket. The potential role of this lipid in regulating THIK-1 therefore deserves further investigation because microglia can sense a variety of extracellular lipids that stimulate their inflammatory response and changes in linoleic acid have been shown to influence microglial activity 29,30 .…”