Abstract

Introduction: Bariatric surgery (BS) is considered the most effective intervention for severe obesity (BMI ≥40 kg/m2 or ≥35 kg/m2 with comorbidities) to maintain long-term weight loss and glycemic control, and remission of comorbidities. Objective: To analyze factors associated with BC results: Eating behavior, and genetic polymorphisms rs1800497 ANKK1, rs1799732 DRD2, rs9939609, rs9930506 and rs1421085 of the FTO gene and rs17782313 of the MC4R gene with total weight loss (TBWL), weight and post-surgical BMI.

Methods: We retrospectively selected 101 patients who underwent Roux-en-Y gastric bypass (RYGB) to register their body mass index (BMI), blood pressure, biochemistry characteristics and comorbidities. Post-surgery, Patients were summoned to record anthropometry, blood pressure and apply the questionnaire (eating behavior (TFEQ-R18). Metabolic and hormonal parameters were measured, and the polymorphisms were genotyped.

Results: After 6 (4 – 8) years post-surgery, the total weight loss was 34.7 kg, the BMI post-surgery was 33.8 kg/m2. Bariatric surgery induced an 82% remission of T2DM and a remission of hypertension in 78% of post-surgery patients. We found that current weight negatively correlated with schooling (r=-0.29, p=0.02). Eating behavior (TFEQ-R18) was associated with the total weight lost (p=0.006), and with the polymorphism rs1800497 ANKK1 [OR = 1.13 (1.02–1.25; p=0.009)], while rs1799732 DRD2 and rs17782313 MC4R were not associated with any variable. Post-surgery weight was higher in carriers of the risk genotypes rs9939609 and rs1421085 polymorphisms. The total weight loss was lower in carriers of the risk haplotype rs9939609 and rs9930506. The FTO genotypes influence the insulin levels and HOMA-IR.

Conclusions: The rs1800497 polymorphism of the ANKK1 gene was associated with eating behavior and education was negatively correlated with BMI, which could be considered predictors of the outcome of bariatric surgery. An interaction effect of the risk genotypes rs9930506 and rs1421085 on weight and BMI in response to bariatric surgery was observed.

Abstract:

Progesterone is a female sex hormone that is essential for successful establishment of pregnancy. Its level rises sharply following ovulation and is sustainably high during the uterine receptivity period, a time when the blastocyst implant. Under progesterone influence, several changes occur in the endometrium to ensure successful blastocyst implantation. These include changes to the uterine fluid microenvironment including reduce fluid volume as well as changes to its ionic composition. Studies have shown that these changes are mediated through the effect of progesterone on expression of ion transporters’ genes and proteins including its effect in upregulating the epithelial sodium channel (ENaC), sodium-potassium ATPase pump (Na⁺/K⁺-ATPase) and sodium-calcium exchanger (NCX), as well as in downregulating the expression of Cystic Fibrosis transmembrane regulator (CFTR), a chloride channel that is known to suppress the ENaC activity in endometrial luminal and glandular epithelium. Progesterone has also been found to upregulate the expression of gene and protein for aquaporin channel subunits AQP-5 and AQP-7 in the uterine luminal epithelium. This hormone might also increase the ENaC open channel probability which directly increases ENaC activity. The consequence of ENaC upregulation and increased ENaC activity would be increased Na⁺ reabsorption followed by water reabsorption from the uterine lumen, thus reduces the uterine fluid volume which will subsequently help to bring the blastocyst closer to the uterine luminal epithelium, initiating the attachment phase of blastocyst implantation. Meanwhile, increased Na⁺ reabsorption will also create a net positive charge in the uterine luminal epithelium that will attract the negatively charged blastocyst towards the uterine wall. Additionally, the efflux of Na⁺ from the uterine epithelium will trigger the influx of Ca²⁺ and subsequently will stimulate the intracellular Ca²⁺ release. Apart from this, progesterone has been found to trigger the release of Ca²⁺ from the intracellular stores, directly. Increased intracellular Ca²⁺ levels will activate the intracellular signalling pathways that initiate decidualization. In conclusion, progesterone is an essential hormone in early phase of blastocyst implantation and its deficiency would results in failure to establish clinical pregnancy.