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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c76ba490337d4d6ea06ec89d31cd8b29
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c76ba490337d4d6ea06ec89d31cd8b29
record_format	dspace
spelling	oai:doaj.org-article:c76ba490337d4d6ea06ec89d31cd8b292021-12-02T17:25:44ZRole of myeloid cell leptin signaling in the regulation of glucose metabolism10.1038/s41598-021-97549-02045-2322https://doaj.org/article/c76ba490337d4d6ea06ec89d31cd8b292021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97549-0https://doaj.org/toc/2045-2322Abstract 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.Sandra PereiraDaemon L. ClineMelissa ChanKalin ChaiJi Soo YoonShannon M. O’DwyerCara E. EllisMaria M. GlavasTravis D. WebberRobert K. BakerSuheda ErenerScott D. CoveyTimothy J. KiefferNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	role of myeloid cell leptin signaling in the regulation of glucose metabolism
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c76ba490337d4d6ea06ec89d31cd8b29
work_keys_str_mv	AT sandrapereira roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT daemonlcline roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT melissachan roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT kalinchai roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT jisooyoon roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT shannonmodwyer roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT caraeellis roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT mariamglavas roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT travisdwebber roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT robertkbaker roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT suhedaerener roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT scottdcovey roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism AT timothyjkieffer roleofmyeloidcellleptinsignalingintheregulationofglucosemetabolism
_version_	1718380935069564928

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

Ejemplares similares