Thesis defense Samuel Frey

Obesity is a major public health issue which concerns approximately 20% of the population worldwide. It is associated with multiple comorbidities including diabetes and dyslipidemia. Bariatric surgeries, which constantly evolve, have emerged as an efficient therapy, allowing content weight loss and metabolic benefits. This work aimed to decipher the molecular mechanisms involved in the hypocholesterolemic effects of bariatric surgeries.

    In a first time, we studied the role of a major actor of the cholesterol metabolism, the intestinal low-density lipoprotein receptor (LDLR), on the hypocholesterolemic effects of the Roux-en-Y gastric bypass (RYGB), which is the gold standard procedure. We showed that, in mice, the intestinal LDLR deficiency was associated with a reduced hypocholerolemic effect after RYGB related to a higher intestinal cholesterol absorption and altered fecal bile acids excretion.
 In a second time, we developped, for the first time in mice, the  Single anastomosis Duodeno-ileal Bypass with Sleeve gastrectomy (SADI-S), a recently described procedure with a high metabolic impact. This model allowed durable weight loss.
    The comparison between SADI-S and RYGB in Ob/Ob mice showed that the former induced a higher weight loss and metabolic benefits. The strong hypocholesterolemic impact of SADI-S was associated with decreased intestinal cholesterol absorption and an increased plasma cholesterol epuration.
    Finally, promising preliminary results suggest that the prevention of hypercholesterolemia induced by a cholesterol-enrichied diet in mice carriying a LDLR deficiency (prone to develop atherosclerosis) is associated with a reduced progression of the atherosclerotic plaques in male mice.