期刊
ISCIENCE
卷 25, 期 9, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2022.104994
关键词
-
资金
- NIH [P01AT003961, P20GM103641, R01ES030144, R01AI129788, R01AI160896, R01AI123947]
This study investigates the role of CB1 in immune and non-immune cells during diet-induced obesity (DIO). The results show that CB1 in non-immune cells is necessary for induction of DIO, while CB1 in immune cells exacerbates DIO and leads to other metabolic abnormalities.
While blockade of cannabinoid receptor 1 (CB1) has been shown to attenuate diet-induced obesity (DIO), its relative role in different cell types has not been tested. The current study investigated the role of CB1 in immune vs non-immune cells during DIO by generating radiation-induced bone marrow chimeric mice that expressed functional CB1 in all cells except the immune cells or expressed CB1 only in immune cells. CB1(-/-) recipient hosts were resistant to DIO, indicating that CB1 in non-immune cells is necessary for induction of DIO. Interestingly, chimeras with CB1(-/-) in immune cells showed exacerbation in DIO combined with infiltration of bone-marrow-derived macrophages to the brain and visceral adipose tissue, elevated food intake, and increased glucose intolerance. These results demonstrate the opposing role of CB1 in hematopoietic versus non-hematopoietic cells during DIO and suggests that targeting immune CB1 receptors provides a new pathway to ameliorate obesity and related metabolic disorders.
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