Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

VIP deficient mice are resistant to diet-induced obesity (DIO); sex-specific differences dependent on genotype and time of diet exposure

Obesity is a 21st-century epidemic that afflicts more than 42% of adults worldwide, and is associated with several comorbidities, including type 2 diabetes and heart disease. Vasoactive intestinal peptide (VIP) is a metabolic gut hormone involved in energy homeostasis. Research has revealed that VIP’s amino acid sequence is 100% identical across most mammals, including humans, rodents and livestock. Our lab reported in 2019 that VIP-deficient mice exhibited gut microbiota dysbiosis consistent with microbiome shifts observed in inflammatory bowel disease mouse models, which also suffer from weight loss. Moreover, VIP-deficient mice are leaner compared to wild-type (WT) littermates, prompting us to hypothesize that VIP-deficient mice are resistant to diet-induced obesity (DIO). Our data revealed that VIP KO mice were highly resistant to DIO gaining only ≈40% body weight compared to WT littermates (p≤0.0001). Also, we observed a sex-specific difference with male HETs resistant to DIO (p≤0.01), while female KO mice gained more weight early (weeks 1-4), but less weight later (weeks 8-12, p≤0.0001) than males. These data strongly support our hypothesis, and understanding the role of VIP in DIO could provide a promising therapeutic approach for mitigating human obesity.