Research Papers:

Administration of alpha-ketoglutarate improves epithelial restitution under stress injury in early-weaning piglets

Liuqin He, Xihong Zhou, Niu Huang, Huan Li, Zhijie Cui, Junquan Tian, Qian Jiang, Shaojuan Liu, Jian Wu, Tiejun Li, Kang Yao and Yulong Yin _

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Oncotarget. 2017; 8:91965-91978. https://doi.org/10.18632/oncotarget.20555

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Liuqin He1,2,*, Xihong Zhou1,*, Niu Huang3, Huan Li3, Zhijie Cui4, Junquan Tian1,2, Qian Jiang1,2, Shaojuan Liu1,2, Jian Wu1,2, Tiejun Li1,5, Kang Yao1,5 and Yulong Yin1,5,6

1Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, Hunan 410125, China

2University of Chinese Academy of Sciences, Beijing, 10039, China

3College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China

4Xiangtan University, Xiangtan, Hunan 411105, China

5Hunan Co-Innovation Center of Animal Production Safety, Changsha, Hunan, 410128, China

6Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410006, China

*These authors have contributed equally to this work

Corresponding to:

Yulong Yin, email: [email protected]

Kang Yao, email: [email protected]

Keywords: AKG, inflammatory cytokines, nutrient-sensing transporters, tight-junction proteins, epithelial restitution

Received: May 10, 2017    Accepted: August 07, 2017    Published: August 24, 2017


Alpha-ketoglutarate (AKG) is an important cellular metabolite that participates in energy production and amino acid metabolism. However, the protective effects and mechanism of AKG on mucosal lesions have not been well understood. This study was conducted to investigate the effects of dietary AKG supplementation on epithelial restitution in early-weaning piglets under Escherichia coli lipopolysaccharide (LPS) induction. A total of 32 weaned piglets were used in a 2 × 2 factorial design; the major factors were dietary treatment (basal diet or AKG diet) and inflammatory challenge (LPS or saline). The results showed that AKG supplementation improved the growth performance and intestinal morphology in the LPS-induced early-weaning piglets. Compared with the basal diet, the AKG diet remarkably decreased the concentration and mRNA expression of intestinal inflammatory cytokines (IL-1β, IL-6, and IL-12) in the LPS-induced piglets. Moreover, AKG administration upregulated the mRNA expression of nutrient-sensing transporters (GLUT-2, SGLT-1, PEPT-1, I-FABP2) in the small intestine of both saline- and LPS-treated piglets, and improved the distribution and expression of tight-junction genes andproteins (ZO-1, Occludin, Claudins, E-cadherin). Collectively, our findings indicate that AKG has the potential to alleviate intestinal inflammatory response and improve epithelial restitution and nutrient-sensing ability under stress injury in early-weaning piglets, and it also provides an experimental basis for enteral use of AKG in swine production and clinical application to prevent intestinal epithelial damage.

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