Summary of Study ST001743

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001116. The data can be accessed directly via it's Project DOI: 10.21228/M8FM51 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001743
Study TitleThe Role of Intestinal-derived FGF15 and Vertical Sleeve Gastrectomy on Plasma Bile Acid Composition in Mice
Study TypeMS analysis
Study SummaryBariatric surgeries such as the Vertical Sleeve Gastrectomy (VSG) are invasive but provide the most effective long-term metabolic improvements in individuals with obesity and/or Type 2 diabetes. These powerful effects of manipulating the gastrointestinal tract point to an important role of gastrointestinal signals in regulating both energy balance and metabolism. To that end, we have used mouse models of VSG to identify key gut signals that mediate these beneficial effects. Previous data from our rodent model of VSG led us to hypothesize a potential role for the hormone Fibroblast-Growth Factor15/19 (mouse/human ortholog) which pharmacologically can regulate many aspects of energy homeostasis and glucose handling. FGF15 is expressed in ileal enterocytes of the small intestine and is released postprandially. Like many other gut hormones, postprandial plasma concentrations of the human ortholog FGF19 and ileal FGF15 expression in mice increase after VSG. We generated intestinal-specific FGF15 knock out (VilCreERT2; Fgf15f/f) mice and controls, which were maintained on 60% high-fat diet. VSG resulted in increased plasma bile acid levels. However, intestinal-specific FGF15 knock out mice had considerably higher levels of circulating total and hydrophobic bile acids after VSG. Unlike what we had predicted, intestinal-specific FGF15 knock out mice lost more weight after VSG as a result of increased lean tissue loss compared to control mice. Further, the loss of bone mineral density and bone marrow adipose tissue observed after VSG in control mice was even greater in intestinal-specific FGF15 knock out mice, perhaps secondary to anemia and elevated erythropoietin/FGF23. Finally the effect of VSG to improve glucose tolerance and to reduce hepatic cholesterol was also absent in intestinal-specific FGF15 knock out mice. These data point to an important role for intestinal FGF15 to protect the organism from deleterious effects of bile acid toxicity after VSG.
Institute
University of Michigan
DepartmentSurgery
LaboratorySeeley Lab
Last NameSeeley
First NameRandy
AddressAnn Arbor, MI, 48105, USA
Emailseeleyrj@umich.edu
Phone734-615-2880
Submit Date2021-04-13
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2021-04-29
Release Version1
Randy Seeley Randy Seeley
https://dx.doi.org/10.21228/M8FM51
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001116
Project DOI:doi: 10.21228/M8FM51
Project Title:The Role of Intestinal-derived FGF15 and Vertical Sleeve Gastrectomy on Plasma Bile Acid Composition in Mice
Project Summary:Bariatric surgeries such as the Vertical Sleeve Gastrectomy (VSG) are invasive but provide the most effective long-term metabolic improvements in individuals with obesity and/or Type 2 diabetes. These powerful effects of manipulating the gastrointestinal tract point to an important role of gastrointestinal signals in regulating both energy balance and metabolism. To that end, we have used mouse models of VSG to identify key gut signals that mediate these beneficial effects. Previous data from our rodent model of VSG led us to hypothesize a potential role for the hormone Fibroblast-Growth Factor15/19 (mouse/human ortholog) which pharmacologically can regulate many aspects of energy homeostasis and glucose handling. FGF15 is expressed in ileal enterocytes of the small intestine and is released postprandially. Like many other gut hormones, postprandial plasma concentrations of the human ortholog FGF19 and ileal FGF15 expression in mice increase after VSG. We generated intestinal-specific FGF15 knock out (VilCreERT2; Fgf15f/f) mice and controls, which were maintained on 60% high-fat diet. VSG resulted in increased plasma bile acid levels. However, intestinal-specific FGF15 knock out mice had considerably higher levels of circulating total and hydrophobic bile acids after VSG. Unlike what we had predicted, intestinal-specific FGF15 knock out mice lost more weight after VSG as a result of increased lean tissue loss compared to control mice. Further, the loss of bone mineral density and bone marrow adipose tissue observed after VSG in control mice was even greater in intestinal-specific FGF15 knock out mice, perhaps secondary to anemia and elevated erythropoietin/FGF23. Finally the effect of VSG to improve glucose tolerance and to reduce hepatic cholesterol was also absent in intestinal-specific FGF15 knock out mice. These data point to an important role for intestinal FGF15 to protect the organism from deleterious effects of bile acid toxicity after VSG.
Institute:University of Michigan
Department:MRC2
Laboratory:Metabolomics core
Last Name:Kachman
First Name:Maureen
Address:1000 Wall St., 5458
Email:mkachman@med.umich.edu
Phone:734-232-0842
Funding Source:NIH: 1U2CDK110678-01, P30-AR069620, P30 DK089503, DK097153, 5T32DK108740, 5T32DK071212-12, UL1TR002240, DK020572, DK089503, DK107282, DK121995, RO1 DK62876 , R24 DK092759, American Diabetes Association grants 1-19-IBS-252 and 1-18-PDF-087

Subject:

Subject ID:SU001820
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Male

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype Surgery
SA163266S00046252CTRL Sham
SA163267S00046233CTRL Sham
SA163268S00046245CTRL Sham
SA163269S00046240CTRL Sham
SA163270S00046248CTRL Sham
SA163271S00046241CTRL VSG
SA163272S00046242CTRL VSG
SA163273S00046239CTRL VSG
SA163274S00046234CTRL VSG
SA163275S00046250CTRL VSG
SA163276S00046237CTRL VSG
SA163277S00046254CTRL VSG
SA163278S00046251FGF15INT-KO Sham
SA163279S00046257FGF15INT-KO Sham
SA163280S00046244FGF15INT-KO Sham
SA163281S00046238FGF15INT-KO Sham
SA163282S00046247FGF15INT-KO Sham
SA163283S00046236FGF15INT-KO Sham
SA163284S00046235FGF15INT-KO VSG
SA163285S00046256FGF15INT-KO VSG
SA163286S00046253FGF15INT-KO VSG
SA163287S00046232FGF15INT-KO VSG
SA163288S00046249FGF15INT-KO VSG
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Collection:

Collection ID:CO001813
Collection Summary:Mouse blood collection
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR001833
Treatment Summary:HFD diet after sham or VSG surgery

Sample Preparation:

Sampleprep ID:SP001826
Sampleprep Summary:Standard bile acid analysis sample prep
Sampleprep Protocol Filename:Bile_Acids_Assay.pdf

Combined analysis:

Analysis ID AN002836
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 6410
Column Waters XBridge C18 (150mm x 2.1mm,3.5um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Agilent 6410 QQQ
Ion Mode NEGATIVE
Units nM

Chromatography:

Chromatography ID:CH002099
Instrument Name:Agilent 6410
Column Name:Waters XBridge C18 (150mm x 2.1mm,3.5um)
Chromatography Type:Reversed phase

MS:

MS ID:MS002629
Analysis ID:AN002836
Instrument Name:Agilent 6410 QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Agilent Data Acquisition/Agilent Quant
Ion Mode:NEGATIVE
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