Vazquez Roque Maria I, Camilleri Michael, Clark Matthew M, Tepoel Debra A, Jensen Michael D, Graszer Karen M, Kalsy Sarah A, Burton Duane D, Baxter Kari L, Zinsmeister Alan R
Clinical Enteric Neuroscience Translational and Epidemiological Research Group, Gastroenterology Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Clin Gastroenterol Hepatol. 2007 Jul;5(7):829-37. doi: 10.1016/j.cgh.2007.02.037. Epub 2007 Jun 4.
BACKGROUND & AIMS: It is unclear whether weight loss with the noradrenergic (norepinephrine) and serotonergic (5-hydroxytryptamine) reuptake inhibitor, sibutramine, is associated with altered stomach functions and whether genetics influence treatment response.
Forty-eight overweight and obese but otherwise healthy participants were randomized to placebo or sibutramine (15 mg/day for 12 weeks). At baseline and posttreatment we measured the following: gastric emptying for solids and liquids by scintigraphy, gastric volumes by single-photon emission computed tomography, maximum tolerated volume and 30-minute postnutrient challenge symptoms, and selected gastrointestinal hormones. All participants received structured behavior therapy for weight management. The influence of candidate gene polymorphisms involved in norepinephrine and 5-hydroxytryptamine or receptor function (phenylethanolamine N-methyltransferase, guanine nucleotide binding protein beta polypeptide 3, alpha2A adrenoreceptor, and solute carrier family 6 [neurotransmitter transporter, serotonin] member 4 [homo sapiens] [SLC6A4]) on weight loss and gastric functions was evaluated.
The overall average weight loss posttreatment was 5.4 +/- 0.8 (SEM) kg with sibutramine and 0.9 +/- 0.9 kg with placebo (P < .001). The sibutramine group showed significant retardation in gastric emptying of solids (P = .03), reduced maximum tolerated volume (P = .03), and increased postprandial peptide YY compared with the placebo group. Obese females showed greater effects of sibutramine on weight loss and gastric emptying of solids and liquids. Gastric volumes and postchallenge symptoms were not significantly different in the 2 treatment groups. The LS/SS genotype of the promoter for SLC6A4 was associated with enhanced weight loss with sibutramine.
Weight reduction with sibutramine is associated with altered gastric functions and increased peptide YY and is significantly associated with SLC6A4 genotype. The role of genetic variation in SLC6A4 on weight loss in response to sibutramine deserves further study.
尚不清楚去甲肾上腺素能（去甲肾上腺素）和5-羟色胺能（5-羟色胺）再摄取抑制剂西布曲明引起的体重减轻是否与胃功能改变相关，以及基因是否影响治疗反应。
48名超重和肥胖但其他方面健康的参与者被随机分为安慰剂组或西布曲明组（15毫克/天，共12周）。在基线和治疗后，我们测量了以下指标：通过闪烁扫描法测量固体和液体的胃排空、通过单光子发射计算机断层扫描测量胃容积、最大耐受量和营养物激发后30分钟的症状，以及选定的胃肠激素。所有参与者均接受了体重管理的结构化行为疗法。评估了参与去甲肾上腺素和5-羟色胺或受体功能的候选基因多态性（苯乙醇胺N-甲基转移酶、鸟嘌呤核苷酸结合蛋白β多肽3、α2A肾上腺素能受体和溶质载体家族6 [神经递质转运体，5-羟色胺] 成员4 [智人] [SLC6A4]）对体重减轻和胃功能的影响。
治疗后，西布曲明组的总体平均体重减轻为5.4±0.8（标准误）千克，安慰剂组为0.9±0.9千克（P <.001）。与安慰剂组相比，西布曲明组的固体胃排空明显延迟（P =.03），最大耐受量降低（P =.03），餐后肽YY增加。肥胖女性中西布曲明对体重减轻以及固体和液体胃排空的影响更大。两个治疗组的胃容积和激发后症状无显著差异。SLC6A4启动子的LS/SS基因型与西布曲明引起的体重减轻增加相关。
西布曲明引起的体重减轻与胃功能改变和肽YY增加相关，并且与SLC6A4基因型显著相关。SLC6A4基因变异在西布曲明引起的体重减轻中的作用值得进一步研究。
