靶向代谢组学分析揭示，膳食超营养硒调节猪肝脏中糖和酰基辅酶 A 代谢稳态。

Targeted Metabolomics Analysis Reveals that Dietary Supranutritional Selenium Regulates Sugar and Acylcarnitine Metabolism Homeostasis in Pig Liver.

机构信息

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, China.

Scientific Observing and Experiment Station of Animal Genetic Resources and Nutrition in North China of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, China.

出版信息

J Nutr. 2020 Apr 1;150(4):704-711. doi: 10.1093/jn/nxz317.

DOI:10.1093/jn/nxz317

PMID:32060554

Abstract

BACKGROUND

The association between high selenium (Se) intake and metabolic disorders such as type 2 diabetes has raised great concern, but the underlying mechanism remains unclear.

OBJECTIVE

Through targeted metabolomics analysis, we examined the liver sugar and acylcarnitine metabolism responses to supranutritional selenomethionine (SeMet) supplementation in pigs.

METHODS

Thirty-six castrated male pigs (Duroc-Landrace-Yorkshire, 62.0 ± 3.3 kg) were fed SeMet adequate (Se-A, 0.25 mg Se/kg) or SeMet supranutritional (Se-S, 2.5 mg Se/kg) diets for 60 d. The Se concentration, biochemical, gene expression, enzyme activity, and energy-targeted metabolite profiles were analyzed.

RESULTS

The Se-S group had greater fasting serum concentrations of glucose (1.9-fold), insulin (1.4-fold), and free fatty acids (FFAs,1.3-fold) relative to the Se-A group (P < 0.05). The liver total Se concentration was 4.2-fold that of the Se-A group in the Se-S group (P < 0.05), but expression of most selenoprotein genes and selenoenzyme activity did not differ between the 2 groups. Seven of 27 targeted sugar metabolites and 4 of 21 acylcarnitine metabolites significantly changed in response to high SeMet (P < 0.05). High SeMet supplementation significantly upregulated phosphoenolpyruvate carboxy kinase (PEPCK) activity by 64.4% and decreased hexokinase and succinate dehydrogenase (SDH) activity by 46.5-56.7% (P < 0.05). The relative contents of glucose, dihydroxyacetone phosphate, α-ketoglutarate, fumarate, malate, erythrose-4-phosphate, and sedoheptulose-7-phosphate in the Se-S group were 21.1-360% greater than those in the Se-A group (P < 0.05). The expression of fatty acid synthase (FASN) and the relative contents of carnitine, hexanoyl-carnitine, decanoyl-carnitine, and tetradecanoyl-carnitine in the Se-S group were 35-97% higher than those in the Se-A group (P < 0.05).

CONCLUSIONS

Dietary high SeMet-induced hyperglycemia and hyperinsulinemia were associated with suppression of sugar metabolism and elevation of lipid synthesis in pig livers. Our research provides novel insights into high SeMet intake-induced type 2 diabetes.

摘要

背景

高硒（Se）摄入与 2 型糖尿病等代谢紊乱之间的关联引起了极大关注，但潜在机制尚不清楚。

目的

通过靶向代谢组学分析，我们研究了超营养硒蛋氨酸（SeMet）补充对猪肝脏糖和酰基辅酶 A 代谢的影响。

方法

36 头去势雄性猪（杜洛克-长白-约克夏，62.0±3.3kg）分别饲喂 SeMet 适宜（Se-A，0.25mg Se/kg）或 SeMet 超营养（Se-S，2.5mg Se/kg）日粮 60d。分析 Se 浓度、生化指标、基因表达、酶活性和能量靶向代谢物谱。

结果

与 Se-A 组相比，Se-S 组空腹血清葡萄糖（1.9 倍）、胰岛素（1.4 倍）和游离脂肪酸（FFAs，1.3 倍）浓度更高（P<0.05）。Se-S 组肝脏总 Se 浓度是 Se-A 组的 4.2 倍（P<0.05），但两组大多数硒蛋白基因的表达和硒酶活性没有差异。27 种靶向糖代谢物中有 7 种和 21 种酰基辅酶 A 代谢物中有 4 种对高 SeMet 有显著变化（P<0.05）。高 SeMet 补充使磷酸烯醇丙酮酸羧激酶（PEPCK）活性显著升高 64.4%，而使己糖激酶和琥珀酸脱氢酶（SDH）活性降低 46.5-56.7%（P<0.05）。Se-S 组葡萄糖、二羟丙酮磷酸、α-酮戊二酸、延胡索酸、苹果酸、赤藓糖-4-磷酸和景天庚酮糖-7-磷酸的相对含量比 Se-A 组高 21.1-360%（P<0.05）。脂肪酸合成酶（FASN）的表达和肉碱、己酰肉碱、癸酰肉碱和肉豆蔻酰肉碱的相对含量在 Se-S 组分别比 Se-A 组高 35-97%（P<0.05）。