TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high-fat diet

Rahul M. Kakalij, Del L. Dsouza, Li Gyeom Ha, Erika I. Boesen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere15949
JournalPhysiological Reports
Volume12
Issue number3
DOIs
StatePublished - Feb 2024

Keywords

  • autoimmunity
  • hyperglycemia
  • imiquimod
  • metabolic syndrome
  • toll-like receptor 7

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'TLR7 activation by imiquimod worsens glycemic control in female FVB/N mice consuming a high-fat diet'. Together they form a unique fingerprint.

Cite this