Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil.
Universidade Federal do Rio de Janeiro (UFRJ), Campus UFRJ-Macaé, Macaé, RJ, Brazil.
Life Sci. 2017 Nov 1;188:68-75. doi: 10.1016/j.lfs.2017.08.035. Epub 2017 Sep 1.
Hypothalamic obesity is a severe condition without any effective therapy. Bariatric operations appear as an alternative treatment, but the effects of this procedure are controversial. We, herein, investigated the effects of duodeno-jejunal bypass (DJB) surgery upon the lipid profile and expression of genes and proteins, involved in the regulation of hepatic lipid metabolism, in hypothalamic obese (HyO) rats.
During the first 5days of life, male newborn Wistar rats received subcutaneous injections of monosodium glutamate [4g/kg body weight, HyO group] or saline (control, CTL group). At 90days of life, HyO rats were randomly submitted to DJB (HyO DJB) or Sham-operations (HyO Sham group). Six months after DJB, adiposity, hepatic steatosis and lipid metabolism were verified.
HyO Sham rats were obese, hyperinsulinemic, insulin resistant and dyslipidemic. These rats had higher liver contents of trygliceride (TG) and presented disorganization of the hepatocyte structures, in association with higher hepatic contents of acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), and stearoyl-CoA desaturase-1 mRNAs and protein. DJB surgery normalized insulinemia, insulin resistance, and dyslipidemia in HyO rats. TG content in the liver and the hepatic microscopic structures were also normalized in HyO DJB rats, while the expressions of ACC and FASN proteins were decreased in the liver of these rodents.
The DJB-induced amelioration in hepatic steatosis manifested as a late effect in HyO rats, and was partly associated with a downregulation in hepatic de novo lipogenesis processes, indicating that DJB protects against liver steatosis in hypothalamic obesity.
下丘脑性肥胖是一种没有任何有效治疗方法的严重疾病。减重手术似乎是一种替代治疗方法，但这种手术的效果存在争议。在此，我们研究了十二指肠空肠旁路（DJB）手术对下丘脑肥胖（HyO）大鼠肝脏脂质代谢调节相关基因和蛋白表达及血脂谱的影响。
新生雄性 Wistar 大鼠在出生后第 5 天接受谷氨酸单钠[4g/kg 体重，HyO 组]或生理盐水（对照，CTL 组）皮下注射。90 天后，HyO 大鼠随机接受 DJB（HyO DJB）或假手术（HyO Sham 组）。DJB 术后 6 个月，验证肥胖、肝脂肪变性和脂质代谢。
HyO Sham 大鼠肥胖、高胰岛素血症、胰岛素抵抗和血脂异常。这些大鼠肝组织甘油三酯（TG）含量升高，肝细胞结构紊乱，乙酰辅酶 A 羧化酶（ACC）、脂肪酸合酶（FASN）和硬脂酰辅酶 A 去饱和酶-1 mRNA 和蛋白含量升高。DJB 手术使 HyO 大鼠的胰岛素血症、胰岛素抵抗和血脂异常正常化。HyO DJB 大鼠肝 TG 含量和肝微观结构也正常化，而这些啮齿动物肝组织中 ACC 和 FASN 蛋白的表达降低。
DJB 诱导的 HyO 大鼠肝脂肪变性改善表现为晚期效应，部分与肝从头合成脂质过程下调有关，表明 DJB 可预防下丘脑肥胖性肝脂肪变性。
