Steun ons werk
Decorative header background

Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity

Onderzoeksgroep Kalsbeek
Publicatiejaar 2017
Gepubliceerd in Cell Reports
Auteur(s) Yuanqing Gao, Andrés Vidal-Itriago, Martin J Kalsbeek, Clarita Layritz, Cristina García-Cáceres, Robby Zachariah Tom, Thomas O Eichmann, Frédéric M Vaz, Riekelt H Houtkooper, Nicole van der Wel, Arthur J Verhoeven, Jie Yan, A. Kalsbeek, Robert H Eckel, Susanna M Hofmann, Chun-Xia Yi

Consumption of a hypercaloric diet upregulates microglial innate immune reactivity along with a higher expression of lipoprotein lipase (Lpl) within the reactive microglia in the mouse brain. Here, we show that knockdown of the Lpl gene specifically in microglia resulted in deficient microglial uptake of lipid, mitochondrial fuel utilization shifting to glutamine, and significantly decreased immune reactivity. Mice with knockdown of the Lpl gene in microglia gained more body weight than control mice on a high-carbohydrate high-fat (HCHF) diet. In these mice, microglial reactivity was significantly decreased in the mediobasal hypothalamus, accompanied by downregulation of phagocytic capacity and increased mitochondrial dysmorphologies. Furthermore, HCHF-diet-induced POMC neuronal loss was accelerated. These results show that LPL-governed microglial immunometabolism is essential to maintain microglial function upon exposure to an HCHF diet. In a hypercaloric environment, lack of such an adaptive immunometabolic response has detrimental effects on CNS regulation of energy metabolism.

Steun ons werk

De Stichting Vrienden van het Herseninstituut ondersteunt baanbrekend hersenonderzoek. U kunt ons daarbij helpen.

Steun ons werk

Wij, hersenonderzoekers, willen het brein nog beter begrijpen en zo doorbraken realiseren in de behandeling van ziektes als MS, Parkinson, Alzheimer en depressie. Om onze missie te volbrengen, willen wij ons volledig concentreren op ons onderzoek. Wil je ons daarbij helpen?

Doe een donatie of  schrijf je in voor onze nieuwsbrief!

Hartelijk dank!