Modulation of Gr1low monocyte subset impacts insulin sensitivity and weight gain upon high-fat diet in female mice - Sorbonne Université Accéder directement au contenu
Article Dans Une Revue International Journal of Obesity Année : 2017

Modulation of Gr1low monocyte subset impacts insulin sensitivity and weight gain upon high-fat diet in female mice

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Background/Objectives: Blood monocytes are expanded during obesity. However, the differential contribution of monocyte subsets in obesity-related metabolic disorders remains unknown. The aim of the study was to define the role of the Gr1low monocyte subset upon high-fat diet (HFD). Methods: We used transgenic female mouse models allowing the modulation of circulating Gr1low monocyte number (decreased number in CX3CR1−/− mice and increased number in CD11c-hBcl2 mice) and studied obesity upon HFD. Results: We reported here that HFD induced monocytosis in mice, preferentially due to Gr1low monocyte expansion, and was associated with a specific upregulation of CD11c on that subset. Using mice models with altered Gr1low monocyte number, we found a striking correlation between Gr1low monocytes, bodyweight (BW) and insulin resistance (RT) status. Indeed, CX3CR1−/− female mice, with reduced Gr1low monocytes upon HFD, showed increased RT and a pro-inflammatory profile of the adipose tissue (AT) despite a lower BW. Conversely, mice expressing the anti-apoptotic gene hBcl2 in CD11c-expressing cells have increased Gr1low monocytes, higher insulin sensitivity upon HFD and an anti-inflammatory profile of the AT. Finally, increasing Gr1low monocytes in Gr1low-defective CX3CR1−/− mice rescued BW loss in these mice. Conclusions: By using transgenic female mice and adoptive transfer experiments, we established the evidence for a correlation between Gr1low monocyte subset and weight gain and RT. Hence, this specific Gr1low monocyte subset could be used as a target for acting on AT inflammation and RT.
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hal-01580410 , version 1 (01-09-2017)

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Sophie Béliard, L Le Goff, F Saint-Charles, P Poupel, V Deswaerte, et al.. Modulation of Gr1low monocyte subset impacts insulin sensitivity and weight gain upon high-fat diet in female mice. International Journal of Obesity, 2017, ⟨10.1038/ijo.2017.179⟩. ⟨hal-01580410⟩
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