Theranostics 2019; 9(3):721-733. doi:10.7150/thno.31562 This issue Cite

Research Paper

Fto Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice via Alterations in Gut Microbiota

Lijuan Sun1,2, Lanjing Ma1, Haohao Zhang1, Ying Cao1, Chenchen Wang1, Nannan Hou3, Niu Huang3, Karen M. von Deneen4, Changhai Zhao2, Yupeng Shi5, Yan Pan5, Meixia Wang5, Gang Ji5, Yongzhan Nie1,5✉

1. State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an 710032, China.
2. Department of Clinical Nutrition, Xijing Hospital, The Fourth Military Medical University, Xi׳an, 710032, China.
3. National Institute of Biological Sciences, Number 7 Science Park Road, Zhongguancun Life Science Park, Beijing, MI 102206, China.
4. Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710126, China
5. Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China.

Citation:
Sun L, Ma L, Zhang H, Cao Y, Wang C, Hou N, Huang N, von Deneen KM, Zhao C, Shi Y, Pan Y, Wang M, Ji G, Nie Y. Fto Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice via Alterations in Gut Microbiota. Theranostics 2019; 9(3):721-733. doi:10.7150/thno.31562. https://www.thno.org/v09p0721.htm
Other styles

File import instruction

Abstract

Graphic abstract

Depression and obesity have high concurrence within individuals, which may be explained by sharing the same risk factors, including disruption of the intestinal microbiota. However, evidence that delineated the causal connections is extremely scarce.

Methods: Mice lacking fat mass- and obesity-associated gene (Fto) were generated. Fto-deficient and wild-type control mice were subjected to novel conditions with or without chronic unpredictable mild stress (CUMS) for 6 weeks. Some mice were treated with antibiotics via their drinking water for 6 weeks in order to deplete their microbiota. Behavioral tests were performed to evaluate anxiety- and depression-like behaviors. 16S rRNA amplicon and metagenomic sequencing were employed to analyse fecal microbiota. Plasma levels of inflammatory cytokines and lipopolysaccharides (LPS) were also compared.

Results: Deletion of Fto led to lower body weight and decreased anxiety- and depression-like behaviors, Fto+/- mice were also less susceptible to stress stimulation, highlighting the essential role of Fto in pathogenesis of depression. With regard to gut microbiota, Fto deficiency mice harbored specific bacterial signature of suppressing inflammation, characterized with higher abundance of Lactobacillus, lower Porphyromonadaceae and Helicobacter. Critically, behavioral alterations of Fto+/- mice are mediated by shift in gut microbiota, as such changes can be partially attenuated using antibiotics. Exposure to CUMS increased serum IL-6 level while Fto deficiency reduced its level, which may be explained by a lower LPS concentration.

Conclusion: Together, our findings uncover the roles of Fto on depression and provide insights into microbiota-related biological mechanisms underlying the association between obesity and depression.

Keywords: Fto, Obesity, Depression, Microbiota, Lactobacillus


Citation styles

APA
Sun, L., Ma, L., Zhang, H., Cao, Y., Wang, C., Hou, N., Huang, N., von Deneen, K.M., Zhao, C., Shi, Y., Pan, Y., Wang, M., Ji, G., Nie, Y. (2019). Fto Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice via Alterations in Gut Microbiota. Theranostics, 9(3), 721-733. https://doi.org/10.7150/thno.31562.

ACS
Sun, L.; Ma, L.; Zhang, H.; Cao, Y.; Wang, C.; Hou, N.; Huang, N.; von Deneen, K.M.; Zhao, C.; Shi, Y.; Pan, Y.; Wang, M.; Ji, G.; Nie, Y. Fto Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice via Alterations in Gut Microbiota. Theranostics 2019, 9 (3), 721-733. DOI: 10.7150/thno.31562.

NLM
Sun L, Ma L, Zhang H, Cao Y, Wang C, Hou N, Huang N, von Deneen KM, Zhao C, Shi Y, Pan Y, Wang M, Ji G, Nie Y. Fto Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice via Alterations in Gut Microbiota. Theranostics 2019; 9(3):721-733. doi:10.7150/thno.31562. https://www.thno.org/v09p0721.htm

CSE
Sun L, Ma L, Zhang H, Cao Y, Wang C, Hou N, Huang N, von Deneen KM, Zhao C, Shi Y, Pan Y, Wang M, Ji G, Nie Y. 2019. Fto Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice via Alterations in Gut Microbiota. Theranostics. 9(3):721-733.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image