Dietary flavonoid kaempferol reduces obesity-associated hypothalamic microglia activation and promotes body weight loss in mice with obesity.

BACKGROUND: Obesity results from an unbalance in the ingested and burned calories. Energy balance (EB) is critically regulated by the hypothalamic arcuate nucleus (ARC) by promoting appetite or anorectic actions. Hypothalamic inflammation, driven by high activation of the microglia, has been reported as a key mechanism involved in the development of diet-induced obesity. Kaempferol (KF), a flavonoid-type polyphenol present in a large number of fruits and vegetables, was shown to regulate both energy metabolism and inflammation. OBJECTIVES: In this work, we studied the effects of both the central and peripheral treatment with KF on hypothalamic inflammation and EB regulation in mice with obesity. METHODS: Obese adult mice were chronically (40 days) treated with KF (0.5 mg/kg/day, intraperitoneally). During the treatment, body weight, food intake (FI), feed efficiency (FE), glucose tolerance, and insulin sensitivity were determined. Analysis of microglia activation in the ARC of the hypothalamus at the end of the treatment was also performed. Body weight, FI, and FE changes were also evaluated in response to 5µg KF, centrally administrated. RESULTS: Chronic administration of KF decreased ∼43% of the density, and ∼30% of the ratio, of activated microglia in the arcuate nucleus. These changes were accompanied by body weight loss, decreased FE, reduced fasting blood glucose, and a tendency to improve insulin sensitivity. Finally, acute central administration of KF reproduced the effects on EB triggered by peripheral administration. CONCLUSION: These findings suggest that KF might fight obesity by regulating central processes related to EB regulation and hypothalamic inflammation.

Early Life Stress Activates Glial Cells in the Hippocampus but Attenuates Cytokine Secretion in Response to an Immune Challenge in Rat Pups.

OBJECTIVE: Early life stress (ELS) increases the vulnerability to developing psychopathological disorders in adulthood that are accompanied by brain inflammatory processes. However, it is not known how a combined double hit (stress and immune) at an early age affects the response of the neuroimmune system. Here we investigated the effect of periodic maternal separation (MS) followed by administration of lipopolysaccharide (LPS) on glial cells in the CA3 region and hilus of the hippocampus and on cytokine release on postnatal day (PN) 15. METHODS: Male rat pups were subjected to MS (3 h/day, PN1-14). MS and control pups received a single LPS injection (1 mg/kg of body weight) on PN14. They were subjected to an open field test 1 h later. The pups were sacrificed 90 min after LPS injection (PN14) or on PN15 for cytokine or immunohistological analyses, respectively. RESULTS: LPS reduced the locomotion and induced high corticosterone levels in treated pups. MS or LPS reduced microglial density and activated microglial cells in the hippocampal CA3 and hilus regions. Microglial activation was highest in MS-LPS pups. The astrocyte density was mildly reduced by MS or LPS in the CA3 region and hilus, but the reduction was maximal in MS-LPS pups. LPS increased the secretion of plasmatic interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6, and of hippocampal IL-1ß protein, but these were attenuated in MS-LPS pups. CONCLUSION: Although MS and LPS activate neuroimmune cells, stress attenuates the hippocampal and peripheral cytokine response to LPS through an as-yet unidentified adaptive mechanism. These results provide information regarding the neurobiology of stress and inflammation.