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

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

Margit Wunderlich  1 , Manuel Miller  2 , Bärbel Ritter  1 , Ronan Le Gleut  3 , Hannah Marchi  4 , Monir Majzoub-Altweck  5 , Patrick J Knerr  6 , Jonathan D Douros  6 , Timo D Müller  7 , Markus Brielmeier  1
Affiliations

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

Margit Wunderlich et al. Mol Metab. 2024 Sep.

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.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
Pre-diabetes development under HFD feeding. A Body weight development, n = 26–27; B Blood glucose, n = 26–27; C Insulin, n = 17–26; D TAG, n = 18–26; E Cholesterol; n = 18–26, p < 0.05∗, p < 0.01∗∗, and p < 0.001∗∗∗, n.s. = not significant.
Figure 4
Figure 4
Glucose tolerance after 6 h fasting. A ipGTT liraglutide; B ipGTT MAR709; C ipGTT vehicle; D AUC liraglutide; E AUC MAR709; F AUC vehicle; G AUC SOPF mice; H AUC colonized mice; n = 8–9, p < 0.05∗, p < 0.01∗∗, and p < 0.001∗∗∗, n.s. = not significant.
Figure 2
Figure 2
Body weight and food intake under treatment with incretin-analogues. A Body weight (%) liraglutide; B Body weight (%) MAR709; C Body weight (%) vehicle; D Body weight (%) grouped; E Food intake (g) liraglutide; F Food intake (g) MAR709; G Food intake (g) vehicle; H Food intake (g) grouped; n = 8–9, p < 0.05∗, p < 0.01∗∗, and p < 0.001∗∗∗, n.s. = not significant.
Figure 3
Figure 3
Fat mass and lean mass under treatment with incretin-analogues. A Fat mass (%) liraglutide; B Fat mass (%) MAR709; C Fat mass (%) vehicle; D Fat mass (%) SOPF mice; E Fat mass (%) colonized mice; F Lean mass (%) liraglutide; G Lean mass (%) MAR709; H Lean mass (%) vehicle; I Lean mass (%) SOPF mice; J Lean mass (%) colonized mice; n = 8–9, p < 0.05∗, p < 0.01∗∗, and p < 0.001∗∗∗, n.s. = not significant.
Figure 5
Figure 5
Steatosis scores according to Brunt et al. and Kleiner et al. [44,45]. A Score 0 normal; B Score 1 mild; C Score 2 moderate; D Score 3 severe.
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