Oncotarget

Research Papers: Pathology:

Alpha-ketoglutarate (AKG) lowers body weight and affects intestinal innate immunity through influencing intestinal microbiota

Shuai Chen, Peng Bin, Wenkai Ren, Wei Gao, Gang Liu _, Jie Yin, Jielin Duan, Yinghui Li, Kang Yao, Ruilin Huang, Bie Tan and Yulong Yin

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Oncotarget. 2017; 8:38184-38192. https://doi.org/10.18632/oncotarget.17132

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Abstract

Shuai Chen1,2,3,4,5,6,*, Peng Bin1,2,3,4,5,6,*, Wenkai Ren1,2,3,4,5, Wei Gao1,2,3,4,5, Gang Liu1,2,3,4,5, Jie Yin1,2,3,4,5,6, Jielin Duan1,2,3,4,5,6, Yinghui Li1,2,3,4,5,6, Kang Yao1,2,3,4,5, Ruilin Huang1,2,3,4,5, Bie Tan1,2,3,4,5 and Yulong Yin1,2,3,4,5

1 Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China

2 National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan, China

3 Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Hunan, China

4 Scientific Observation and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan, China

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

6 University of Chinese Academy of Sciences, Beijing, China

* These authors have contributed equally to this work

Correspondence to:

Gang Liu, email:

Keywords: alpha-ketoglutarate; cryptdin; intestinal microbiota; intestinal immunity; Pathology Section

Received: October 24, 2016 Accepted: April 04, 2017 Published: April 16, 2017

Abstract

Alpha-ketoglutarate (AKG), a precursor of glutamate and a critical intermediate in the tricarboxylic acid cycle, shows beneficial effects on intestinal function. However, the influence of AKG on the intestinal innate immune system and intestinal microbiota is unknown. This study explores the effect of oral AKG administration in drinking water (10 g/L) on intestinal innate immunity and intestinal microbiota in a mouse model. Mouse water intake, feed intake and body weight were recorded throughout the entire experiment. The ileum was collected for detecting the expression of intestinal proinflammatory cytokines and innate immune factors by Real-time Polymerase Chain Reaction. Additionally, the ileal luminal contents and feces were collected for 16S rDNA sequencing to analyze the microbial composition. The intestinal microbiota in mice was disrupted with an antibiotic cocktail. The results revealed that AKG supplementation lowered body weight, promoted ileal expression of mammalian defensins of the alpha subfamily (such as cryptdins-1, cryptdins-4, and cryptdins-5) while influencing the intestinal microbial composition (i.e., lowering the Firmicutes to Bacteroidetes ratio). In the antibiotic-treated mouse model, AKG supplementation failed to affect mouse body weight and inhibited the expression of cryptdins-1 and cryptdins-5 in the ileum. We concluded that AKG might affect body weight and intestinal innate immunity through influencing intestinal microbiota.


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