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Animal Models

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

Abstract

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.

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Acknowledgements

We thank Marie Liabeuf and Stephanie Lemarchand-Minde (Animal facility, l'Institut du Thorax, Nantes, France) for their help in the setting of the animals care protocol. This work was supported by grants from: La région des Pays de la Loire; the fondation d’avenir; the Casden bank; the AFC; the Fondation Leducq Grant (13CVD03).

Author contributions

CB, FM, BC and CLM: designed the study; CB, FM, AA, LT, FB, DG, LA, AA, MC, MK and CLM: performed the experiments and collected the data; CB, FM, AA, LT, FB, DG, XP, MN, BC and CLM: analyzed the data and arranged the figures; CB, BC and CLM: wrote the first draft of the manuscript. FM, XP and MN: initially reviewed the manuscript. All authors edited and approved the final draft of the manuscript.

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Correspondence to C Le May.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Blanchard, C., Moreau, F., Ayer, A. et al. Roux-en-Y gastric bypass reduces plasma cholesterol in diet-induced obese mice by affecting trans-intestinal cholesterol excretion and intestinal cholesterol absorption. Int J Obes 42, 552–560 (2018). https://doi.org/10.1038/ijo.2017.232

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