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

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 303; no. 5; p. G589
• Main Authors: de Wit, Nicole, Derrien, Muriel, Bosch-Vermeulen, Hanneke, Oosterink, Els, Keshtkar, Shohreh, Duval, Caroline, de Vogel-van den Bosch, Johan, Kleerebezem, Michiel, Müller, Michael, van der Meer, Roelof
• Format: Journal Article
• Language: English
• Published: United States 01-09-2012
• Subjects: Animals; Dietary Fats - pharmacology; Fatty Acids - pharmacology; Fatty Liver - genetics; Fatty Liver - metabolism; Gene Expression - drug effects; Intestines - drug effects; Intestines - metabolism; Intestines - microbiology; Liver - metabolism; Metabolic Syndrome - genetics; Metabolic Syndrome - metabolism; Metagenome; Mice; Mice, Inbred C57BL; Obesity - genetics; Obesity - metabolism
• ISSN: 1522-1547
• DOI: 10.1152/ajpgi.00488.2011

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.