Glucose Intolerance and Lipid Metabolic Adaptations in Response to Intrauterine and Postnatal Calorie Restriction in Male Adult Rats
Glucose Intolerance and Lipid Metabolic Adaptations in Response to Intrauterine and Postnatal Calorie Restriction in Male Adult Rats
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DOI：
10.1210/en.2012-1640
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发表时间：
2013-01-01
期刊：
影响因子：
4.8
通讯作者：
Devaskar, Sherin U.
中科院分区：
文献类型：
--
作者：
Garg, Meena;Thamotharan, Manikkavasagar;Devaskar, Sherin U.
高碳水化合物或低脂饮食可增强肝脏新生脂肪生成（DNL），这是一种成人肝脏适应。我们假设产前热量限制后的随意摄入会导致成人发病的葡萄糖耐受不良，并通过改变脂质代谢基因表达谱增强DNL。在产前（IUGR）、产前和产后（IPGR）或产后（PNGR）热量限制与对照组（CON）的对比中，对15个月大的成年雄性大鼠后代使用了稳定同位素。IUGR组比CON组更重，肝肿大，但内脏白色脂肪组织（WAT）不变，葡萄糖不耐受，葡萄糖刺激胰岛素分泌（GSIS）减少，胰腺β细胞质量和总葡萄糖清除率，但未抑制肝葡萄糖生成。肝脏葡萄糖转运蛋白（Glut） 1和DNL随着肝脏乙酰辅酶a羧化酶（ACC）和脂肪酸合成酶的降低而升高，而WAT脂肪酸转运蛋白-1和过氧化物酶体增殖物激活受体、抵抗素和内脏素基因表达升高。相比之下，PNGR和IPGR更轻，内脏WAT减少，葡萄糖耐受性不变，肝脏葡萄糖产量不变，但GSIS， β细胞质量，葡萄糖清除率和WAT胰岛素受体增加。在瘦IPGR和PNGR中，肝脏Glut1和DNL也增加，肝脏ACC、磷酸化ACC和pAMPK增加，WAT脂肪酸转运蛋白-1、过氧化物酶体增殖物激活受体- γ和ACC α减少。我们得出以下结论：1)出生后热量限制可改善重度、葡萄糖不耐受和胰岛素抵抗的IUGR成人表型；2)与肝脏Glut1平行的DNL升高是早期热量限制暴露的生物标志物，而不是成年代谢状态的生物标志物；3)肝脂酶表达反映GSIS而非DNL；4) WAT基因表达反映了肥胖与瘦弱表型。（journal of Endocrinology）， 2013。
Enhanced de novo lipogenesis (DNL), an adult hepatic adaption, is seen with high carbohydrate or low-fat diets. We hypothesized that ad libitum intake after prenatal calorie restriction will result in adult-onset glucose intolerance and enhanced DNL with modified lipid metabolic gene expression profile. Stable isotopes were used in 15-month-old adult male rat offspring exposed to prenatal (IUGR), pre- and postnatal (IPGR), or postnatal (PNGR) caloric restriction vs. controls (CON). IUGR vs. CON were heavier with hepatomegaly but unchanged visceral white adipose tissue (WAT), glucose intolerant with reduced glucose-stimulated insulin secretion (GSIS), pancreatic beta-cell mass, and total glucose clearance rate but unsuppressed hepatic glucose production. Liver glucose transporter (Glut) 1 and DNL increased with decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase but increased WAT fatty acid transport protein-1 and peroxisomal proliferator-activated receptor-gamma, resistin, and visfatin gene expression. In contrast, PNGR and IPGR were lighter, had reduced visceral WAT, and were glucose tolerant with unchanged hepatic glucose production but with increased GSIS, beta-cell mass, glucose clearance rate, and WAT insulin receptor. Hepatic Glut1 and DNL were also increased in lean IPGR and PNGR with increased hepatic ACC, phosphorylated ACC, and pAMPK and reduced WAT fatty acid transport protein-1, peroxisomal proliferator-activated receptor-gamma, and ACC alpha. We conclude the following: 1) the heavy, glucose-intolerant and insulin-resistant IUGR adult phenotype is ameliorated by postnatal caloric restriction; 2) increased DNL paralleling hepatic Glut1 is a biomarker of exposure to early caloric restriction rather than the adult metabolic status; 3) hepatic lipid enzyme expression reflects GSIS rather than DNL; and 4) WAT gene expression reflects an obesogenic vs. lean phenotype. (Endocrinology 154: 102-113, 2013)