Role of myeloid cell leptin signaling in the regulation of glucose metabolism.

Autor: Pereira S; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Cline DL; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Chan M; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Chai K; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Yoon JS; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., O'Dwyer SM; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Ellis CE; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Glavas MM; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Webber TD; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Baker RK; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Erener S; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Covey SD; Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Kieffer TJ; Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. tim.kieffer@ubc.ca.; Department of Surgery, University of British Columbia, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada. tim.kieffer@ubc.ca.; School of Biomedical Engineering, University of British Columbia, 251-2222 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. tim.kieffer@ubc.ca.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Sep 15; Vol. 11 (1), pp. 18394. Date of Electronic Publication: 2021 Sep 15.
DOI: 10.1038/s41598-021-97549-0
Abstrakt: Although innate immunity is linked to metabolic health, the effect of leptin signaling in cells from the innate immune system on glucose homeostasis has not been thoroughly investigated. We generated two mouse models using Cre-lox methodology to determine the effect of myeloid cell-specific leptin receptor (Lepr) reconstitution and Lepr knockdown on in vivo glucose metabolism. Male mice with myeloid cell-specific Lepr reconstitution (Lyz2Cre + Lepr loxTB/loxTB ) had better glycemic control as they aged compared to male mice with whole-body transcriptional blockade of Lepr (Lyz2Cre - Lepr loxTB/loxTB ). In contrast, Lyz2Cre + Lepr loxTB/loxTB females only had a trend for diminished hyperglycemia after a prolonged fast. During glucose tolerance tests, Lyz2Cre + Lepr loxTB/loxTB males had a mildly improved plasma glucose profile compared to Cre - controls while Lyz2Cre + Lepr loxTB/loxTB females had a similar glucose excursion to their Cre - controls. Myeloid cell-specific Lepr knockdown (Lyz2Cre + Lepr flox/flox ) did not significantly alter body weight, blood glucose, insulin sensitivity, or glucose tolerance in males or females. Expression of the cytokine interleukin 10 (anti-inflammatory) tended to be higher in adipose tissue of male Lyz2Cre + Lepr loxTB/loxTB mice (p = 0.0774) while interleukin 6 (pro-inflammatory) was lower in male Lyz2Cre + Lepr flox/flox mice (p < 0.05) vs. their respective controls. In conclusion, reconstitution of Lepr in cells of myeloid lineage has beneficial effects on glucose metabolism in male mice.
(© 2021. The Author(s).)
Databáze: MEDLINE