TY - JOUR
T1 - Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity
AU - Gao, Yuanqing
AU - Vidal-Itriago, Andrés
AU - Kalsbeek, Martin J.
AU - Layritz, Clarita
AU - García-Cáceres, Cristina
AU - Tom, Robby Zachariah
AU - Eichmann, Thomas O.
AU - Vaz, Frédéric M.
AU - Houtkooper, Riekelt H.
AU - van der Wel, Nicole
AU - Verhoeven, Arthur J.
AU - Yan, Jie
AU - Kalsbeek, Andries
AU - Eckel, Robert H.
AU - Hofmann, Susanna M.
AU - Yi, Chun-Xia
PY - 2017
Y1 - 2017
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.celrep.2017.09.008
DO - https://doi.org/10.1016/j.celrep.2017.09.008
M3 - Article
C2 - 28954222
SN - 2211-1247
VL - 20
SP - 3034
EP - 3042
JO - Cell reports
JF - Cell reports
IS - 13
ER -