Chronic refined low-fat diet consumption reduces cholecystokinin satiation in rats
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.
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 1H-NMR-based metabolomics. CCK satiation was evaluated by measuring the suppression of food intake after intraperitoneal CCK injection (1 or 3 µg/kg).
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.
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.
KeywordsObesity Gut-brain axis Metabolomics Vagal afferents Food intake
The authors would like to thank Cécile Canlet from the French National Infrastructure of Metabolomics and Fluxomics (MetaboHUB-ANR-11-INBS-0010) for her help with the NMR facility and Dr. Olivier Cloarec from Korrigan Sciences Limited for providing the matlab functions for analysis of NMR data. They also want to thank Ricky Stephens for his help in animal experiment.
MG, MKH, CCR, HER, and GB designed research; MG, MKH, CCR, and SES conducted research; MG and SES analyzed data; MG, MKH, SES, HER, and GB wrote the paper. GB had primarily responsibility for final content. All authors read and approved final version.
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest to declare.
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