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Updated: Aug 10, 2025
Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
MSR1 is not required for obesity-associated inflammation and insulin resistance in mice
Sierra A Nance1,2, Lindsey Muir3, Jennifer Delproprosto2
1Molecular and Integrative Physiology, University of Michigan Medical School, 109 Zina Pitcher Place, 2057 BSRB, Ann Arbor, MI, 48109, USA.
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.
Insights
Macrophage scavenger receptor 1 (MSR1) is a biomarker for diabetes in human adipose tissue. However, MSR1 is not required for obesity-related insulin resistance or adipose tissue macrophage accumulation in mice.
Area of Science:
- Metabolism
- Immunology
- Endocrinology
Background:
- Obesity triggers chronic inflammation, altering adipose tissue macrophages (ATMs).
- Macrophage scavenger receptor 1 (MSR1) role in adipose tissue inflammation and diabetes is debated.
- MSR1 expression is elevated in visceral adipose tissue (VAT) of obese diabetic individuals.
Purpose of the Study:
- To investigate the role of MSR1 in obesity-induced inflammation and glucose intolerance.
- To determine if MSR1 deficiency protects against obesity and associated metabolic dysfunction in mice.
Main Methods:
- Utilized Msr1 knockout (Msr1KO) and wild-type (WT) mice models.
- Administered high-fat diets to induce obesity and insulin resistance.
- Analyzed body weight, glucose metabolism, insulin resistance, and ATM populations via flow cytometry.
Main Results:
- Msr1KO mice showed protection from obesity and adipose tissue inflammation initially, but this was not observed in littermate comparisons.
- Obese Msr1KO and heterozygous (Msr1HET) mice exhibited similar obesity and insulin resistance compared to WT controls.
- No significant differences in ATM subtypes or proliferation were found between genotypes, though obese females had more proliferating ATMs than males.
Conclusions:
- MSR1 serves as a biomarker for diabetes in human adipose tissue.
- MSR1 is dispensable for the development of obesity-associated insulin resistance and ATM accumulation in mice.
- Obesity in female mice is associated with increased ATM proliferation compared to males.
