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

• Published in: The Journal of nutrition Vol. 150; no. 4; pp. 704 - 711
• Main Authors: Zhang, Kai, Han, Yunsheng, Zhao, Qingyu, Zhan, Tengfei, Li, Ying, Sun, Wenjuan, Li, Shuang, Sun, Dandan, Si, Xueyang, Yu, Xiaonan, Qin, Yuchang, Tang, Chaohua, Zhang, Junmin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2020; Oxford University Press; American Institute of Nutrition
• Subjects: Animals; Carnitine; Carnitine - analogs & derivatives; Carnitine - metabolism; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - chemically induced; Diet; Dietary Supplements; Dihydroxyacetone; Dihydroxyacetone phosphate; Dose-Response Relationship, Drug; Enzymatic activity; Enzyme activity; Fatty acids; Fatty-acid synthase; Gene expression; Glucose; Hexokinase; Homeostasis; Homeostasis - drug effects; Hyperglycemia; Hyperglycemia - chemically induced; Hyperinsulinemia; Hyperinsulinism - chemically induced; Insulin; Kinases; Lipid metabolism; Lipids; Lipids - biosynthesis; Liver; Liver - chemistry; Liver - enzymology; Liver - metabolism; Malate; Male; Metabolic disorders; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; Models, Animal; Oxidation-Reduction; pig; RNA, Messenger - analysis; Selenium; Selenium - administration & dosage; Selenium - adverse effects; Selenium - analysis; Selenomethionine; Selenomethionine - administration & dosage; Selenomethionine - adverse effects; Selenoproteins - genetics; SeMet; Succinate dehydrogenase; Sugar; sugar and acylcarnitine metabolism; Sugars - metabolism; supranutritional supplementation; Sus scrofa; Se-A; ACSS2; PEPCK; sugar and acylcarnitine metabolism; liver; SeMet; IS; supranutritional supplementation; GPX; pig; TC; MDH; LDH; TXNRD; FASN; SDH; SELENOW; SREBF; Se-S
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/nxz317

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