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Knud Erik Bach Knudsen

Mice Fed a High-Fat Diet Supplemented with Resistant Starch Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Dorothy A. Kieffer, Univ Calif Davis, University of California Davis, University of California System, Grad Grp Nutr Biol, Univ Calif Davis, University of California Davis, University of California System, Dept Nutr, USDA ARS, United States Department of Agriculture (USDA), Obes & Metab Res Unit, Western Human Nutr Res Ctr
  • ,
  • Brian D. Piccolo, Univ Arkansas Med Sci, University of Arkansas Medical Sciences, University of Arkansas System, Arkansas Childrens Nutr Ctr, Univ Arkansas Med Sci, University of Arkansas Medical Sciences, University of Arkansas System, Dept Pediat
  • ,
  • Maria L. Marco, Univ Calif Davis, University of California Davis, University of California System, Food Sci & Technol Dept
  • ,
  • Eun Bae Kim, Univ Calif Davis, University of California Davis, University of California System, Food Sci & Technol Dept, Kangwon Natl Univ, Kangwon National University, Coll Anim Life Sci, Dept Anim Life Sci
  • ,
  • Michael L. Goodson, Univ Calif Davis, University of California Davis, University of California System, Dept Microbiol
  • ,
  • Michael J. Keenan, Louisiana State Univ, Louisiana State University, Louisiana State University System, AgCtr
  • ,
  • Tamara N. Dunn, Univ Calif Davis, University of California Davis, University of California System, Grad Grp Nutr Biol, Univ Calif Davis, University of California Davis, University of California System, Dept Nutr, USDA ARS, United States Department of Agriculture (USDA), Obes & Metab Res Unit, Western Human Nutr Res Ctr
  • ,
  • Knud Erik Bach Knudsen
  • Roy J. Martin, Univ Calif Davis, University of California Davis, University of California System, Grad Grp Nutr Biol, Univ Calif Davis, University of California Davis, University of California System, Dept Nutr, USDA ARS, United States Department of Agriculture (USDA), Obes & Metab Res Unit, Western Human Nutr Res Ctr
  • ,
  • Sean H. Adams, Univ Calif Davis, University of California Davis, University of California System, Grad Grp Nutr Biol, Univ Calif Davis, University of California Davis, University of California System, Dept Nutr, Univ Arkansas Med Sci, University of Arkansas Medical Sciences, University of Arkansas System, Arkansas Childrens Nutr Ctr, Univ Arkansas Med Sci, University of Arkansas Medical Sciences, University of Arkansas System, Dept Pediat

Background: High-amylose-maize resistant starch type 2 (HAMRS2) is a fermentable dietary fiber known to alter the gut milieu, including the gut microbiota, which may explain the reported effects of resistant starch to ameliorate obesity associated metabolic dysfunction.

Objective: Our working hypothesis was that HAMRS2-induced microbiome changes alter gut-derived signals (i.e., xenometabolites) reaching the liver via the portal circulation, in turn altering liver metabolism by regulating gene expression and other pathways.

Methods: We used a multi-omics systems biology approach to characterize HAMRS2-driven shifts to the cecal microbiome, liver metabolome, and transcriptome, identifying correlates between microbial changes and liver metabolites under obesogenic conditions that, to our knowledge, have not previously been recognized. Five-week-old male C57BL/6J mice were fed an energy-dense 45% lard-based-fat diet for 10 wk supplemented with either 20% HAMRS2 by weight (n = 14) or rapidly digestible starch (control diet; n = 15).

Results: Despite no differences in food intake, body weight, glucose tolerance, fasting plasma insulin, or liver triglycerides, the HAMRS2 mice showed a 15-58% reduction in all measured liver amino acids, except for Gln, compared with control mice. These metabolites were equivalent in the plasma of HAMRS2 mice compared with controls, and transcripts encoding key amino acid transporters were not different in the small intestine or liver, suggesting that HAMRS2 effects were not simply due to lower hepatocyte exposure to systemic amino acids. Instead, alterations in gut microbial metabolism could have affected host nitrogen and amino acid homeostasis: HAMRS2 mice showed a 62% increase (P <0.0001) in 48-h fecal output and a 41% increase (P <0.0001) in fecal nitrogen compared with control mice. Beyond amino acid metabolism, liver transcriptomics revealed pathways related to lipid and xenobiotic metabolism; and pathways related to cell proliferation, differentiation, and growth were affected by HAMRS2 feeding.

Conclusion: Together, these differences indicate that HAMRS2 dramatically alters hepatic metabolism and gene expression concurrent with shifts in specific gut bacteria in C57BL/6J mice.

OriginalsprogEngelsk
TidsskriftThe Journal of Nutrition
Vol/bind146
Nummer12
Sider (fra-til)2476-2490
Antal sider15
ISSN0022-3166
DOI
StatusUdgivet - dec. 2016

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