MSR1 is not required for obesity-associated inflammation and insulin resistance in mice

Abstract Obesity induces a chronic inflammatory state associated with changes in adipose tissue macrophages (ATMs). Macrophage scavenger receptor 1 (MSR1) has been implicated in the regulation of adipose tissue inflammation and diabetes pathogenesis; however, reports have been mixed on the contribut...

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Main Authors: Sierra A. Nance, Lindsey Muir, Jennifer Delproprosto, Carey N. Lumeng
Format: Article
Language:English
Published: Nature Portfolio 2023-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-29736-0
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author Sierra A. Nance
Lindsey Muir
Jennifer Delproprosto
Carey N. Lumeng
author_facet Sierra A. Nance
Lindsey Muir
Jennifer Delproprosto
Carey N. Lumeng
author_sort Sierra A. Nance
collection DOAJ
description Abstract Obesity induces a chronic inflammatory state associated with changes in adipose tissue macrophages (ATMs). Macrophage scavenger receptor 1 (MSR1) has been implicated in the regulation of adipose tissue inflammation and diabetes pathogenesis; however, reports have been mixed on the contribution of MSR1 in obesity and glucose intolerance. We observed increased MSR1 expression in VAT of obese diabetic individuals compared to non-diabetic and single nuclear RNA sequencing identified macrophage-specific expression of MSR1 in human adipose tissue. We examined male Msr1 −/− (Msr1KO) and WT controls and observed protection from obesity and AT inflammation in non-littermate Msr1KO mice. We then evaluated obese littermate Msr1 +/− (Msr1HET) and Msr1KO mice. Both Msr1KO mice and Msr1HET mice became obese and insulin resistant when compared to their normal chow diet counterparts, but there was no Msr1-dependent difference in body weight, glucose metabolism, or insulin resistance. Flow cytometry revealed no significant differences between genotypes in ATM subtypes or proliferation in male and female mice. We observed increased frequency of proliferating ATMs in obese female compared to male mice. Overall, we conclude that while MSR1 is a biomarker of diabetes status in human adipose tissue, in mice Msr1 is not required for obesity-associated insulin resistance or ATM accumulation.
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spelling doaj.art-d40855c6718f4bd4ae7d9f2491e4de5b2023-03-22T10:59:25ZengNature PortfolioScientific Reports2045-23222023-02-0113111010.1038/s41598-023-29736-0MSR1 is not required for obesity-associated inflammation and insulin resistance in miceSierra A. Nance0Lindsey Muir1Jennifer Delproprosto2Carey N. Lumeng3Molecular and Integrative Physiology, University of Michigan Medical SchoolComputational Medicine and Bioinformatics, University of Michigan Medical SchoolDepartment of Pediatrics, University of Michigan Medical SchoolMolecular and Integrative Physiology, University of Michigan Medical SchoolAbstract Obesity induces a chronic inflammatory state associated with changes in adipose tissue macrophages (ATMs). Macrophage scavenger receptor 1 (MSR1) has been implicated in the regulation of adipose tissue inflammation and diabetes pathogenesis; however, reports have been mixed on the contribution of MSR1 in obesity and glucose intolerance. We observed increased MSR1 expression in VAT of obese diabetic individuals compared to non-diabetic and single nuclear RNA sequencing identified macrophage-specific expression of MSR1 in human adipose tissue. We examined male Msr1 −/− (Msr1KO) and WT controls and observed protection from obesity and AT inflammation in non-littermate Msr1KO mice. We then evaluated obese littermate Msr1 +/− (Msr1HET) and Msr1KO mice. Both Msr1KO mice and Msr1HET mice became obese and insulin resistant when compared to their normal chow diet counterparts, but there was no Msr1-dependent difference in body weight, glucose metabolism, or insulin resistance. Flow cytometry revealed no significant differences between genotypes in ATM subtypes or proliferation in male and female mice. We observed increased frequency of proliferating ATMs in obese female compared to male mice. Overall, we conclude that while MSR1 is a biomarker of diabetes status in human adipose tissue, in mice Msr1 is not required for obesity-associated insulin resistance or ATM accumulation.https://doi.org/10.1038/s41598-023-29736-0
spellingShingle Sierra A. Nance
Lindsey Muir
Jennifer Delproprosto
Carey N. Lumeng
MSR1 is not required for obesity-associated inflammation and insulin resistance in mice
Scientific Reports
title MSR1 is not required for obesity-associated inflammation and insulin resistance in mice
title_full MSR1 is not required for obesity-associated inflammation and insulin resistance in mice
title_fullStr MSR1 is not required for obesity-associated inflammation and insulin resistance in mice
title_full_unstemmed MSR1 is not required for obesity-associated inflammation and insulin resistance in mice
title_short MSR1 is not required for obesity-associated inflammation and insulin resistance in mice
title_sort msr1 is not required for obesity associated inflammation and insulin resistance in mice
url https://doi.org/10.1038/s41598-023-29736-0
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