부산대학교 도서관

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 Gr1 monocyte subset upon high-fat diet (HFD). METHODS:: We used transgenic female mouse models allowing the modulation of circulating Gr1 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 Gr1 monocyte expansion, and was associated with a specific upregulation of CD11c on that subset. Using mice models with altered Gr1 monocyte number, we found a striking correlation between Gr1 monocytes, bodyweight (BW) and insulin resistance (RT) status. Indeed, CX3CR1 female mice, with reduced Gr1 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 Gr1 monocytes, higher insulin sensitivity upon HFD and an anti-inflammatory profile of the AT. Finally, increasing Gr1 monocytes in Gr1-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 Gr1 monocyte subset and weight gain and RT. Hence, this specific Gr1 monocyte subset could be used as a target for acting on AT inflammation and RT.