Experimental colonization with H. hepaticus, S. aureus and R. pneumotropicus does not influence the metabolic response to high-fat diet or incretin-analogues in wildtype SOPF mice

Mol Metab. 2024 Sep:87:101992. doi: 10.1016/j.molmet.2024.101992. Epub 2024 Jul 15.

Abstract

Objectives: We here assessed whether typical pathogens of laboratory mice affect the development of diet-induced obesity and glucose intolerance, and whether colonization affects the efficacy of the GLP-1R agonist liraglutide and of the GLP-1/GIP co-agonist MAR709 to treat obesity and diabetes.

Methods: Male C57BL/6J mice were experimentally infected with Helicobacter hepaticus, Rodentibacter pneumotropicus and Staphylococcus aureus and compared to a group of uninfected specific and opportunistic pathogen free (SOPF) mice. The development of diet-induced obesity and glucose intolerance was monitored over a period of 26 weeks. To study the influence of pathogens on drug treatment, mice were then subjected for 6 days daily treatment with either the GLP-1 receptor agonist liraglutide or the GLP-1/GIP co-agonist MAR709.

Results: Colonized mice did not differ from SOPF controls regarding HFD-induced body weight gain, food intake, body composition, glycemic control, or responsiveness to treatment with liraglutide or the GLP-1/GIP co-agonist MAR709.

Conclusions: We conclude that the occurrence of H. hepaticus, R. pneumotropicus and S. aureus does neither affect the development of diet-induced obesity or type 2 diabetes, nor the efficacy of GLP-1-based drugs to decrease body weight and to improve glucose control in mice.

Keywords: C57BL/6J; Diet-induced obesity model; Helicobacter hepaticus; Rodentibacter pneumotropicus; Staphylococcus aureus; Type 2 diabetes.

MeSH terms

  • Animals
  • Diet, High-Fat* / adverse effects
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucose Intolerance* / metabolism
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology
  • Incretins* / metabolism
  • Liraglutide* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Obesity* / metabolism
  • Specific Pathogen-Free Organisms
  • Staphylococcus aureus* / drug effects

Substances

  • Incretins
  • Liraglutide
  • Glucagon-Like Peptide-1 Receptor