ESPEN 2022 Abstract Submission

Topic: Obesity and the metabolic syndrome

Abstract Submission Identifier: ESPEN22-ABS-1918

ALPK1 DELETION PROTECTS FROM BODY WEIGHT GAIN AND GLUCOSE INTOLERANCE INDUCED BY HFD

A. Rolland^*, ¹, A. Lashermes ¹, J. Cadiou ¹, S. Mondot ¹, V. Douard ¹, N. Lapaque ¹

¹MICALIS Institue, INRAE, Jouy-en-Josas, France

Rationale: Activation of pattern recognition receptors (PRR) by microbiota-derived ligands is known to promote adipose tissue inflammation and insulin resistance in dietary-induced obesity. ALPK1 is a newly-described PRR and 3 SNPs within ALPK1 locus were identified to be associated with obesity and BMI. However, the role of ALPK1 in obesity and related diseases as well as the potential underlying mechanisms remained unknown.

Methods: Eight weeks old male wild type (WT) and ALPK1^-/- mice (C57BL/6J) received a standard (NC) or high-fat diet (HFD, 60 kcal from fat) during 12 weeks. Body composition, glucose intolerance, insulin sensitivity, plasmatic lipid profile, cecal microbiota composition and markers of inflammation in adipose tissue have been assessed. Data were analyzed using one-way ANOVA or two-way ANOVA analysis.

Results: ALPK1^-/- gained significantly less weight than the WT under HFD (p <0.01) despite a similar food intake. Fasting glycemia was lower in the ALPK1^-/- than in the WT independently of the diet (p < 0.0001) and ALPK1^-/- displayed a lower glucose intolerance than the WT after 10 weeks of HFD (p < 0.0001) despite a similar insulin sensitivity. After 12 weeks of HFD, total adiposity increase was higher in WT than in ALPK1^-/- and was associated with an increase in TNFα and MCP1 expression levels when compared to WT NC (p <0.005).  Those markers of inflammation remained unchanged in ALPK1^-/- adipose tissue after 12 weeks of HFD.  Adiponectin plasmatic levels were lower in ALPK1^-/- than WT under NC. Analysis of the microbiota composition showed that the relative abundance of Akkermansia increased in response to HFD in WT, but remained undetectable in ALPK1^-/- fed NC or HFD.

Conclusion: These results clearly demonstrate that ALPK1 deletion protects from body weight gain and glucose intolerance induced by HFD. The potential role of ALPK1 signaling pathway in fat storage reduction remain to be clarified.

This study was supported by Young Investigator grant (2019) of Institut national de recherche pour l'agriculture, l'alimentation et l'environnement (INRAE).

Disclosure of Interest: None Declared

Keywords: Innate immunity, insulin resistance, Metabolic syndrome, Obesity