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Alterations to the microbiota–colon–brain axis in high-fat-diet-induced obese mice compared to diet-resistant mice

Journal Article


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Abstract


  • Obesity is underpinned by both genetic and environmental factors, including a high-saturated-fat diet. Some mice develop diet-induced obesity (DIO), but others remain diet resistant (DR) despite intake of the same high-saturated-fat diet, a phenomenon that mimics characteristics of the human obese phenotype. Microbiota–colon–brain axis regulation is important for energy metabolism and cognition. Using DIO and DR mouse models, this study aimed to examine gut microbiota, colonic inflammation and cognitive function to elucidate the role of microbiota–gut–brain regulation in DIO. C57Bl6/J mice fed a chronic saturated-palmitic-acid diet for 22 weeks showed significant body weight gain differences, with the top one third gaining 48% heavier body weight than the lower one third. There was significant reduction in gut microbiota richness and diversity in DIO mice but not in DR mice. At the phylum level, DIO mice had increased abundance of Firmicutes and Antinobacteria, and decreased abundance of Bacterioides and Proteobacteria in gut microbiota. DIO mice exhibited reduced tight junction proteins, increased plasma endotoxin lipopolysaccharide (LPS) and increased inflammation in the colon and liver. Recognition memory and spatial memory were impaired in DIO mice, associated with decreased Bacteroidetes. Further examination showed that hippocampal brain-derived neurotrophic factor was significantly decreased in DIO mice (vs. DR). Conversely, DR mice showed no changes in the above parameters measured. Therefore, gut microbiota, colon inflammation and circulating LPS may play a major role in the development of the obese phenotype and cognitive decline associated with a chronic high-saturated-palmitic-acid diet.

Authors


  •   Zhang, Peng (external author)
  •   Yu, Yinghua
  •   Qin, Yanfang (external author)
  •   Zhou, Yuan (external author)
  •   Tang, Renxian (external author)
  •   Wang, Qingling (external author)
  •   Li, Xiangyang (external author)
  •   Wang, Hongqin
  •   Green, Katrina (Weston-Green)
  •   Huang, Xu-Feng
  •   Zheng, Kuiyang (external author)

Publication Date


  • 2019

Citation


  • Zhang, P., Yu, Y., Qin, Y., Zhou, Y., Tang, R., Wang, Q., Li, X., Wang, H., Weston-Green, K., Huang, X. & Zheng, K. (2019). Alterations to the microbiota–colon–brain axis in high-fat-diet-induced obese mice compared to diet-resistant mice. Journal of Nutritional Biochemistry, 65 54-65.

Scopus Eid


  • 2-s2.0-85059523145

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=2369&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1342

Number Of Pages


  • 11

Start Page


  • 54

End Page


  • 65

Volume


  • 65

Place Of Publication


  • United States

Abstract


  • Obesity is underpinned by both genetic and environmental factors, including a high-saturated-fat diet. Some mice develop diet-induced obesity (DIO), but others remain diet resistant (DR) despite intake of the same high-saturated-fat diet, a phenomenon that mimics characteristics of the human obese phenotype. Microbiota–colon–brain axis regulation is important for energy metabolism and cognition. Using DIO and DR mouse models, this study aimed to examine gut microbiota, colonic inflammation and cognitive function to elucidate the role of microbiota–gut–brain regulation in DIO. C57Bl6/J mice fed a chronic saturated-palmitic-acid diet for 22 weeks showed significant body weight gain differences, with the top one third gaining 48% heavier body weight than the lower one third. There was significant reduction in gut microbiota richness and diversity in DIO mice but not in DR mice. At the phylum level, DIO mice had increased abundance of Firmicutes and Antinobacteria, and decreased abundance of Bacterioides and Proteobacteria in gut microbiota. DIO mice exhibited reduced tight junction proteins, increased plasma endotoxin lipopolysaccharide (LPS) and increased inflammation in the colon and liver. Recognition memory and spatial memory were impaired in DIO mice, associated with decreased Bacteroidetes. Further examination showed that hippocampal brain-derived neurotrophic factor was significantly decreased in DIO mice (vs. DR). Conversely, DR mice showed no changes in the above parameters measured. Therefore, gut microbiota, colon inflammation and circulating LPS may play a major role in the development of the obese phenotype and cognitive decline associated with a chronic high-saturated-palmitic-acid diet.

Authors


  •   Zhang, Peng (external author)
  •   Yu, Yinghua
  •   Qin, Yanfang (external author)
  •   Zhou, Yuan (external author)
  •   Tang, Renxian (external author)
  •   Wang, Qingling (external author)
  •   Li, Xiangyang (external author)
  •   Wang, Hongqin
  •   Green, Katrina (Weston-Green)
  •   Huang, Xu-Feng
  •   Zheng, Kuiyang (external author)

Publication Date


  • 2019

Citation


  • Zhang, P., Yu, Y., Qin, Y., Zhou, Y., Tang, R., Wang, Q., Li, X., Wang, H., Weston-Green, K., Huang, X. & Zheng, K. (2019). Alterations to the microbiota–colon–brain axis in high-fat-diet-induced obese mice compared to diet-resistant mice. Journal of Nutritional Biochemistry, 65 54-65.

Scopus Eid


  • 2-s2.0-85059523145

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=2369&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1342

Number Of Pages


  • 11

Start Page


  • 54

End Page


  • 65

Volume


  • 65

Place Of Publication


  • United States