학술논문
Modulation of Gr1lowmonocyte subset impacts insulin sensitivity and weight gain upon high-fat diet in female mice
Document Type
Article
Author
Source
International Journal of Obesity (formerly International Journal of Obesity and Related Metabolic Disorders); December 2017, Vol. 41 Issue: 12 p1805-1814, 10p
Subject
Language
ISSN
03070565; 14765497
Abstract
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 Gr1lowmonocyte subset upon high-fat diet (HFD).Methods:We used transgenic female mouse models allowing the modulation of circulating Gr1lowmonocyte 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 Gr1lowmonocyte expansion, and was associated with a specific upregulation of CD11c on that subset. Using mice models with altered Gr1lowmonocyte number, we found a striking correlation between Gr1lowmonocytes, bodyweight (BW) and insulin resistance (RT) status. Indeed, CX3CR1−/−female mice, with reduced Gr1lowmonocytes 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 Gr1lowmonocytes, higher insulin sensitivity upon HFD and an anti-inflammatory profile of the AT. Finally, increasing Gr1lowmonocytes 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 Gr1lowmonocyte subset and weight gain and RT. Hence, this specific Gr1lowmonocyte subset could be used as a target for acting on AT inflammation and RT.