TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high‐fat diet
Abstract Toll‐like receptor‐7 (TLR7) activation promotes autoimmunity, and metabolic syndrome (MetS) is a common comorbidity in patients with autoimmune disease. We previously demonstrated hyperinsulinemia in TLR7 agonist imiquimod (IMQ)‐treated, high‐fat diet (HFD)‐fed female C57BL/6 mice. Since mo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.15949 |
| _version_ | 1827349749690269696 |
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| author | Rahul M. Kakalij Del L. Dsouza LiGyeom Ha Erika I. Boesen |
| author_facet | Rahul M. Kakalij Del L. Dsouza LiGyeom Ha Erika I. Boesen |
| author_sort | Rahul M. Kakalij |
| collection | DOAJ |
| description | Abstract Toll‐like receptor‐7 (TLR7) activation promotes autoimmunity, and metabolic syndrome (MetS) is a common comorbidity in patients with autoimmune disease. We previously demonstrated hyperinsulinemia in TLR7 agonist imiquimod (IMQ)‐treated, high‐fat diet (HFD)‐fed female C57BL/6 mice. Since mouse strains differ in susceptibility to MetS and target organ damage, this study investigated whether 12 weeks of exposure to HFD and IMQ promoted MetS, autoimmunity, and target organ damage in female FVB/N mice. Supporting early‐stage autoimmunity, spleen‐to‐tibia ratio, and anti‐nuclear antibodies (ANA) were significantly increased by IMQ. No significant effect of IMQ on urinary albumin excretion or left ventricular hypertrophy was observed. HFD increased liver‐to‐tibia ratio, which was further exacerbated by IMQ. HFD increased fasting blood glucose levels at the end of 12 weeks, but there was no significant effect of IMQ treatment on fasting blood glucose levels at 6 or 12 weeks of treatment. However, oral glucose tolerance testing at 12 weeks revealed impaired glucose tolerance in HFD‐fed mice compared to control diet mice together with IMQ treatment exacerbating the impairment. Accordingly, these data suggest TLR7 activation also exacerbates HFD‐induced dysregulation of glucose handling FVB/N mice, supporting the possibility that endogenous TLR7 activation may contribute to dysglycemia in patients with autoimmune disease. |
| first_indexed | 2024-03-08T00:46:45Z |
| format | Article |
| id | doaj.art-15d4059c270b4e5b9b15242e94b58492 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-08T00:46:45Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-15d4059c270b4e5b9b15242e94b584922024-02-15T06:28:36ZengWileyPhysiological Reports2051-817X2024-02-01123n/an/a10.14814/phy2.15949TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high‐fat dietRahul M. Kakalij0Del L. Dsouza1LiGyeom Ha2Erika I. Boesen3Department of Cellular & Integrative Physiology University of Nebraska Medical Center Omaha Nebraska USADepartment of Cellular & Integrative Physiology University of Nebraska Medical Center Omaha Nebraska USADepartment of Cellular & Integrative Physiology University of Nebraska Medical Center Omaha Nebraska USADepartment of Cellular & Integrative Physiology University of Nebraska Medical Center Omaha Nebraska USAAbstract Toll‐like receptor‐7 (TLR7) activation promotes autoimmunity, and metabolic syndrome (MetS) is a common comorbidity in patients with autoimmune disease. We previously demonstrated hyperinsulinemia in TLR7 agonist imiquimod (IMQ)‐treated, high‐fat diet (HFD)‐fed female C57BL/6 mice. Since mouse strains differ in susceptibility to MetS and target organ damage, this study investigated whether 12 weeks of exposure to HFD and IMQ promoted MetS, autoimmunity, and target organ damage in female FVB/N mice. Supporting early‐stage autoimmunity, spleen‐to‐tibia ratio, and anti‐nuclear antibodies (ANA) were significantly increased by IMQ. No significant effect of IMQ on urinary albumin excretion or left ventricular hypertrophy was observed. HFD increased liver‐to‐tibia ratio, which was further exacerbated by IMQ. HFD increased fasting blood glucose levels at the end of 12 weeks, but there was no significant effect of IMQ treatment on fasting blood glucose levels at 6 or 12 weeks of treatment. However, oral glucose tolerance testing at 12 weeks revealed impaired glucose tolerance in HFD‐fed mice compared to control diet mice together with IMQ treatment exacerbating the impairment. Accordingly, these data suggest TLR7 activation also exacerbates HFD‐induced dysregulation of glucose handling FVB/N mice, supporting the possibility that endogenous TLR7 activation may contribute to dysglycemia in patients with autoimmune disease.https://doi.org/10.14814/phy2.15949autoimmunityhyperglycemiaimiquimodmetabolic syndrometoll‐like receptor 7 |
| spellingShingle | Rahul M. Kakalij Del L. Dsouza LiGyeom Ha Erika I. Boesen TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high‐fat diet Physiological Reports autoimmunity hyperglycemia imiquimod metabolic syndrome toll‐like receptor 7 |
| title | TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high‐fat diet |
| title_full | TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high‐fat diet |
| title_fullStr | TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high‐fat diet |
| title_full_unstemmed | TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high‐fat diet |
| title_short | TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high‐fat diet |
| title_sort | tlr7 activation by imiquimod worsens glycemic control in female fvb n mice consuming a high fat diet |
| topic | autoimmunity hyperglycemia imiquimod metabolic syndrome toll‐like receptor 7 |
| url | https://doi.org/10.14814/phy2.15949 |
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