Bonfleur Maria Lúcia, Ribeiro Rosane Aparecida, Pavanello Audrei, Soster Raul, Lubaczeuski Camila, Cezar Faria Araujo Allan, Boschero Antonio Carlos, Balbo Sandra Lucinei
Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil, CEP: 858119-110,
Obes Surg. 2015 Apr;25(4):656-65. doi: 10.1007/s11695-014-1427-3.
Bariatric operations are frequently used to improve metabolic profile and comorbidities in obese subjects, but the effects of this procedure in hypothalamic-obese (HyO) patients are controversial. Here, using HyO rats, we investigate the effects of duodenal-jejunal bypass (DJB) upon obesity, serum lipid levels, glucose tolerance, and insulin action and secretion.
Hypothalamic obesity was induced in male rats by the administration of monosodium glutamate [4 g/kg body weight (BW), HyO group] during the first 5 days of life. Control (CTL) group received saline (1.25 g/kg BW). At 90 days of age, HyO rats were submitted to DJB (HyO DJB group) or sham surgery. After 2 months, lipid levels, glucose tolerance, obesity parameters, and insulin sensitivity and secretion were verified.
HyO rats displayed obesity, hypertriglyceridemia, hypercholesterolemia, glucose intolerance, and hyperinsulinemia. A higher HOMA-IR and no alteration in the ratio of phospho (p)-Akt related to Akt protein content in the liver, after insulin stimulus, demonstrated that HyO rats were insulin resistant. Islets isolated from HyO rats hypersecreted insulin in response to glucose and carbachol (Cch). At 2 months after DJB, HyO rats still displayed higher fat stores, but showed normal serum lipids and insulin levels. The HyO DJB group displayed better glucose tolerance, associated with a normal hepatic insulin activation of Akt. Normal glucose and Cch-induced insulin secretion was observed in HyO DJB islets.
DJB ameliorated glucose homeostasis, restored hepatic insulin action, and normalized islet function in HyO rats, indicating that this surgery may be useful for the treatment of hypothalamic obesity.
减肥手术常用于改善肥胖患者的代谢状况和合并症，但该手术对下丘脑性肥胖（HyO）患者的影响存在争议。在此，我们使用HyO大鼠，研究十二指肠-空肠旁路术（DJB）对肥胖、血脂水平、糖耐量以及胰岛素作用和分泌的影响。
在雄性大鼠出生后的前5天给予谷氨酸钠[4 g/kg体重（BW），HyO组]以诱导下丘脑性肥胖。对照组（CTL组）接受生理盐水（1.25 g/kg BW）。90日龄时，对HyO大鼠进行DJB手术（HyO DJB组）或假手术。2个月后，检测血脂水平、糖耐量、肥胖参数以及胰岛素敏感性和分泌情况。
HyO大鼠表现出肥胖、高甘油三酯血症、高胆固醇血症、糖耐量异常和高胰岛素血症。胰岛素刺激后，HyO大鼠的肝脏中胰岛素抵抗指数（HOMA-IR）较高，且磷酸化（p）-Akt与Akt蛋白含量的比值无变化，表明HyO大鼠存在胰岛素抵抗。从HyO大鼠分离的胰岛对葡萄糖和卡巴胆碱（Cch）刺激后胰岛素分泌过多。DJB术后2个月，HyO大鼠仍有较高的脂肪储备，但血清脂质和胰岛素水平正常。HyO DJB组糖耐量较好，肝脏中Akt的胰岛素激活正常。在HyO DJB组的胰岛中观察到葡萄糖和Cch诱导的胰岛素分泌正常。
DJB改善了HyO大鼠的葡萄糖稳态，恢复了肝脏胰岛素作用，并使胰岛功能正常化，表明该手术可能对下丘脑性肥胖的治疗有用。
