Targeting macrophage scavenger receptor 1 promotes insulin resistance in obese male mice
| Autor: | Rebecca W. Chan, Emmanuel Denou, Fernando F. Anhê, Joseph F. Cavallari, Dawn M. E. Bowdish, Jonathan D. Schertzer, Kevin P. Foley |
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| Rok vydání: | 2018 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine insulin obesity medicine.medical_specialty Physiology Glucose uptake medicine.medical_treatment Immunology immunometabolism Adipose tissue Inflammation Ligands MSR1 Mice 03 medical and health sciences Insulin resistance Polysaccharides Physiology (medical) Internal medicine medicine Animals glucose Scavenger receptor Original Research 2. Zero hunger business.industry Insulin Scavenger Receptors Class A medicine.disease 3. Good health Mice Inbred C57BL Macrophage receptor with collagenous structure 030104 developmental biology Endocrinology Adipose Tissue inflammation Endocrine and Metabolic Conditons Disorders and Treatments Insulin Resistance medicine.symptom business Adipose Tissue and Obesity |
| Zdroj: | Physiological Reports |
| ISSN: | 2051-817X |
| DOI: | 10.14814/phy2.13930 |
| Popis: | Immune components can bridge inflammatory triggers to metabolic dysfunction. Scavenger receptors sense lipoproteins, but it is not clear how different scavenger receptors alter carbohydrate metabolism during obesity. Macrophage scavenger receptor 1 (MSR1) and macrophage receptor with collagenous structure (MARCO) are scavenger receptors that have been implicated in lipoprotein metabolism and cardiovascular disease. We assessed glucose control, tissue‐specific insulin sensitivity, and inflammation in Msr1‐ and Marco‐deficient mice fed with obesogenic diets. Compared to wild‐type (WT) mice, Msr1 −/− mice had worse blood glucose control that was only revealed after diet‐induced obesity, not in lean mice. Obese Msr1 −/− mice had worse insulin‐stimulated glucose uptake in the adipose tissue, which occurred in the absence of overt differences in adipose inflammation compared to obese WT mice. Msr1 deletion worsened dysglycemia independently from bacterial cell wall insulin sensitizers, such as muramyl dipeptide. MARCO was dispensable for glycemic control in obese mice. Oral administration of the polysaccharide fucoidan worsened glucose control in obese WT mice, but fucoidan had no effect on glycemia in obese Msr1 −/− mice. Therefore, MSR1 is a scavenger receptor responsible for changes in glucose control in response to the environmental ligand fucoidan. Given the interest in dietary supplements and natural products reducing inflammation or insulin resistance in metabolic disease during obesity, our results highlight the importance of understanding which ligand–receptor relationships promote versus those that protect against metabolic disease factors. Our results show that ligand or gene targeting of MSR1 exacerbates insulin resistance in obese mice. |
| Databáze: | OpenAIRE |
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