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

Abstract 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...

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Main Authors: Sandra Pereira, Daemon L. Cline, Melissa Chan, Kalin Chai, Ji Soo Yoon, Shannon M. O’Dwyer, Cara E. Ellis, Maria M. Glavas, Travis D. Webber, Robert K. Baker, Suheda Erener, Scott D. Covey, Timothy J. Kieffer
Format: Article
Language:English
Published: Nature Portfolio 2021-09-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-97549-0
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author Sandra Pereira
Daemon L. Cline
Melissa Chan
Kalin Chai
Ji Soo Yoon
Shannon M. O’Dwyer
Cara E. Ellis
Maria M. Glavas
Travis D. Webber
Robert K. Baker
Suheda Erener
Scott D. Covey
Timothy J. Kieffer
author_facet Sandra Pereira
Daemon L. Cline
Melissa Chan
Kalin Chai
Ji Soo Yoon
Shannon M. O’Dwyer
Cara E. Ellis
Maria M. Glavas
Travis D. Webber
Robert K. Baker
Suheda Erener
Scott D. Covey
Timothy J. Kieffer
author_sort Sandra Pereira
collection DOAJ
description Abstract 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.
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spelling doaj.art-c76ba490337d4d6ea06ec89d31cd8b292022-12-21T19:27:01ZengNature PortfolioScientific Reports2045-23222021-09-0111111810.1038/s41598-021-97549-0Role of myeloid cell leptin signaling in the regulation of glucose metabolismSandra Pereira0Daemon L. Cline1Melissa Chan2Kalin Chai3Ji Soo Yoon4Shannon M. O’Dwyer5Cara E. Ellis6Maria M. Glavas7Travis D. Webber8Robert K. Baker9Suheda Erener10Scott D. Covey11Timothy J. Kieffer12Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Biochemistry and Molecular Biology, University of British ColumbiaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaAbstract 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.https://doi.org/10.1038/s41598-021-97549-0
spellingShingle Sandra Pereira
Daemon L. Cline
Melissa Chan
Kalin Chai
Ji Soo Yoon
Shannon M. O’Dwyer
Cara E. Ellis
Maria M. Glavas
Travis D. Webber
Robert K. Baker
Suheda Erener
Scott D. Covey
Timothy J. Kieffer
Role of myeloid cell leptin signaling in the regulation of glucose metabolism
Scientific Reports
title Role of myeloid cell leptin signaling in the regulation of glucose metabolism
title_full Role of myeloid cell leptin signaling in the regulation of glucose metabolism
title_fullStr Role of myeloid cell leptin signaling in the regulation of glucose metabolism
title_full_unstemmed Role of myeloid cell leptin signaling in the regulation of glucose metabolism
title_short Role of myeloid cell leptin signaling in the regulation of glucose metabolism
title_sort role of myeloid cell leptin signaling in the regulation of glucose metabolism
url https://doi.org/10.1038/s41598-021-97549-0
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