Chronic refined low-fat diet consumption reduces cholecystokinin satiation in rats

Mathilde Guerville (1) , M Kristina Hamilton (2) , Charlotte C Ronveaux (2) , Sandrine Ellero-Simatos (3) , Helen E Raybould (2) , Gaëlle Boudry (1)

1 NuMeCan - Nutrition, Métabolismes et Cancer
2 VetMed - UC Davis - School of Veterinary Medicine [Univ California Davis]
3 ToxAlim-TIM - Toxicologie Intégrative & Métabolisme

Purpose - Reduced ability of cholecystokinin (CCK) to induce satiation contributes to hyperphagia and weight gain in high-fat/high-sucrose (HF/HS) diet-induced obesity, and has been linked to altered gut microbiota. Rodent models of obesity use chow or low-fat (LF) diets as control diets; the latter has been shown to alter gut microbiota and metabolome. We aimed to determine whether LF-diet consumption impacts CCK satiation in rats and if so, whether this is prevented by addition of inulin to LF diet. Methods - Rats (n = 40) were fed, for 8 weeks, a chow diet (chow) or low-fat (10%) or high-fat/high-sucrose (45 and 17%, respectively) refined diets with either 10% cellulose (LF and HF/HS) or 10% inulin (LF-I and HF/HS-I). Caecal metabolome was assessed by H-NMR-based metabolomics. CCK satiation was evaluated by measuring the suppression of food intake after intraperitoneal CCK injection (1 or 3 µg/kg). Results - LF-diet consumption altered the caecal metabolome, reduced caecal weight, and increased IAP activity, compared to chow. CCK-induced inhibition of food intake was abolished in LF diet-fed rats compared to chow-fed rats, while HF/HS diet-fed rats responded only to the highest CCK dose. Inulin substitution ameliorated caecal atrophy, reduced IAP activity, and modulated caecal metabolome, but did not improve CCK-induced satiety in either LF- or HF/HS-fed rats. Conclusions - CCK signaling is impaired by LF-diet consumption, highlighting that caution must be taken when using LF diet until a more suitable refined control diet is identified.

Mots clés: Food intake; Vagal afferents; Obesity; Gut-brain axis; Metabolomics

Domaines: Alimentation et Nutrition; Médecine vétérinaire et santé animale

Mathilde Guerville, M Kristina Hamilton, Charlotte C Ronveaux, Sandrine Ellero-Simatos, Helen E Raybould, et al.. Chronic refined low-fat diet consumption reduces cholecystokinin satiation in rats. European Journal of Nutrition, 2019, 58 (6), pp.2497-2510. ⟨10.1007/s00394-018-1802-2⟩. ⟨hal-01862581⟩