Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine

Nicole de Wit, Muriel Derrien, Hanneke Bosch-Vermeulen, Els Oosterink, Shohreh Keshtkar, Caroline Duval, Johan de Vogel-van den Bosch, Michiel Kleerebezem, Michael Müller, Roelof van der Meer

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249 Citations (Scopus)

Abstract

We studied the effect of dietary fat type, varying in polyunsaturated-to-saturated fatty acid ratios (P/S), on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1), or safflower oil (HF-SO; P/S 7.8) for 8 wk. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared with the HF-OO, HF-SO, or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes- to-Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis.
Original languageEnglish
Pages (from-to)G589-599
Number of pages11
JournalAJP: Gastrointestinal and Liver Physiology
Volume303
Issue number5
DOIs
Publication statusPublished - 1 Sep 2012

Keywords

  • Animals
  • Dietary Fats
  • Fatty Acids
  • Fatty Liver
  • Gene Expression
  • Intestines
  • Liver
  • Metabolic Syndrome X
  • Metagenome
  • Mice
  • Mice, Inbred C57BL
  • Obesity

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