Roux-en-Y gastric bypass reduces plasma cholesterol in diet-induced obese mice by affecting trans-intestinal cholesterol excretion and intestinal cholesterol absorption

• Published in: International Journal of Obesity Vol. 42; no. 3; pp. 552 - 560
• Main Authors: Blanchard, C, Moreau, F, Ayer, A, Toque, L, Garçon, D, Arnaud, L, Borel, F, Aguesse, A, Croyal, M, Krempf, M, Prieur, X, Neunlist, M, Cariou, B, Le May, C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2018; Nature Publishing Group
• Series: Equipe IV
• Subjects: 59; 631/443/319/1642/2037; 631/443/319/1642/393; 631/443/319/2723; 631/443/592/75; 82/58; Absorption; Animal models; Animals; Bile; Body weight; Care and treatment; Cholesterol; Cholesterol - blood; Cholesterol metabolism; Diet; Dyslipidemia; Efflux; Epidemiology; Excretion; Food intake; Gastrectomy; Gastric bypass; Gastric Bypass - methods; Gastrointestinal surgery; Health aspects; Health Promotion and Disease Prevention; High fat diet; Internal Medicine; Intestinal Absorption - physiology; Intestinal bypass; Intestine; Life Sciences; Lipid metabolism; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Mice; Mice, Inbred C57BL; Mice, Obese; Molecular modelling; Obesity; Obesity, Morbid - metabolism; Obesity, Morbid - surgery; original-article; Patient outcomes; Public Health; Reduction; Rodents; Surgery; Obesity; Metabolic symdrome; Fat metabolism; Cardiovascular diseases
• ISSN: 0307-0565; 1476-5497; 1476-5497; 0307-0565
• DOI: 10.1038/ijo.2017.232

Objective: Bariatric surgery appears as the most efficient therapeutic alternative in morbidly obese patients. In addition to its efficiency to decrease body weight, it also improves metabolic complications associated to morbid obesity, including dyslipidemia. Although the cholesterol-lowering effect varies with the bariatric procedures, the underlying molecular mechanisms remain poorly defined. This study aims to assess the consequence of both restrictive (sleeve gastrectomy; SG) and malabsorptive (Roux-en-Y gastric bypass; RYGB) procedures on cholesterol metabolism in mice. Subjects: Ten-week-old C57BL6/J males were fed with a high-fat diet for 8–14 weeks before sleeve or RYGB surgery. Results: SG has a modest and transient effect on plasma cholesterol levels, linked to a reduction in food intake. In contrast, modified RYGB led to a sustained ≈35% reduction in plasma cholesterol concentrations with a drastic increase in fecal cholesterol output. Mechanistically, RYGB exerts a synergystic effect on cholesterol metabolism by inducing the trans-intestinal cholesterol efflux and reducing the intestinal cholesterol absorption. Conclusions: In mice, RYGB, but not sleeve, strongly favors plasma cholesterol elimination by concomitantly increasing trans-intestinal cholesterol excretion and by decreasing intestinal cholesterol absorption. Our models open new perspective for deciphering the hypocholesterolemic effects of bariatric procedures.