Effects of visceral adiposity on glycerol pathways in gluconeogenesis.
Effects of visceral adiposity on glycerol pathways in gluconeogenesis.
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内脏肥胖对糖异生中甘油途径的影响。
DOI：
10.1016/j.metabol.2016.11.008
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发表时间：
2017-02
期刊：
影响因子：
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通讯作者：
Jin ES
中科院分区：
文献类型：
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作者：
Neeland IJ;Hughes C;Ayers CR;Malloy CR;Jin ES
目的：确定口服13C标记甘油用于评估内脏肥胖对肥胖人群糖异生途径的影响的可行性。无2型糖尿病的肥胖(BMI≥30 kg/m2)受试者接受内脏脂肪组织评估，并按增值税中位数将其分层为高增值税空腹(n=3)、低增值税空腹(n=4)和高增值税补足(n=2)组。摄入[U-13C3]甘油和血液样本的参与者随后在3小时内的多个时间点进行了核磁共振波谱分析。[U-13C3]甘油通过肝脏糖异生、磷酸戊糖途径(PPP)和三羧酸(TCA)循环获得的血糖浓缩部分通过葡萄糖的~(13)C核磁共振分析得到。使用混合线性模型来比较不同组之间的葡萄糖13C浓集。平均年龄为49岁，体重指数为40.1 kg/m2，基线血糖为98 mg/dl。在糖异生之前，高达20%的甘油在TCA循环中代谢，所有参与者的PPP活性都很小(占总葡萄糖的1%)。与低VAT空腹组相比，高VAT空腹组血糖13C浓集降低21%(p=0.03)，提示内源性甘油稀释。与高增值税空腹相比，高增值税受试者的葡萄糖13C浓缩率低37%(p=0.02)。与低VAT组相比，高VAT组有降低[1，2-13C2](通过PPP)和[5，6-13C2]/[4，5，6-13C3](通过TCA循环)的趋势。我们应用了一种简单的方法来检测肥胖者甘油的糖异生作用。我们的发现提供了初步证据，证明过多的内脏脂肪扰乱了甘油引起的肝脏糖异生的多条途径。
To determine the feasibility of using oral 13C labeled glycerol at assess effects of visceral adiposity on gluconeogenic pathways in obese humans. Obese (BMI ≥30 kg/m2) participants without type 2 diabetes underwent visceral adipose tissue (VAT) assessment and stratification by median VAT into high VAT-fasting (n=3), low VAT-fasting (n=4), and high VAT-refed (n=2) groups. Participants ingested [U-13C3] glycerol and blood samples were subsequently analyzed at multiple time points over 3 hours by NMR spectroscopy. The fractions of plasma glucose (enrichment) derived from [U-13C3] glycerol via hepatic gluconeogenesis, pentose phosphate pathway (PPP), and tricarboxylic acid (TCA) cycle were assessed using 13C NMR analysis of glucose. Mixed linear models were used to compare 13C enrichment in glucose between groups. Mean age, BMI, and baseline glucose were 49 years, 40.1 kg/m2, and 98 mg/dl, respectively. Up to 20% of glycerol was metabolized in the TCA cycle prior to gluconeogenesis and PPP activity was minor (<1% of total glucose) in all participants. There was a 21% decrease in 13C enrichment in plasma glucose in the high VAT-fasting compared with low VAT-fasting group (p=0.03), suggesting dilution by endogenous glycerol. High VAT-refed participants had 37% less 13C enrichment in glucose compared with high VAT-fasting (p=0.02). There was a trend toward lower [1,2-13C2] (via PPP) and [5,6-13C2]/[4,5,6-13C3] (via TCA cycle) glucose in high VAT versus low VAT groups. We applied a simple method to detect gluconeogenesis from glycerol in obese humans. Our findings provide preliminary evidence that excess visceral fat disrupts multiple pathways in hepatic gluconeogenesis from glycerol.