Skip to main content Accessibility help
×
Home

Microbiome transfer between IL-1RI-/- and wild-type mice during high or low-fat feeding alters metabolic tissue functionality but not glucose homeostasis.

Published online by Cambridge University Press:  10 June 2020


Jessica C. Ralston
Affiliation:
Nutrigenomics Research Group and Institute of Food and Health, University College Dublin, Dublin, Ireland
Kathleen A.J. Mitchelson
Affiliation:
Nutrigenomics Research Group and Institute of Food and Health, University College Dublin, Dublin, Ireland
Gina M. Lynch
Affiliation:
Nutrigenomics Research Group and Institute of Food and Health, University College Dublin, Dublin, Ireland
Tam T.T. Tran
Affiliation:
APC Microbiome Ireland, University College Cork, Cork, Ireland School of Microbiology, University College Cork, Cork, Ireland
Conall R. Strain
Affiliation:
APC Microbiome Ireland, University College Cork, Cork, Ireland Teagasc Food Research Centre, Moorepark, Cork, Ireland
Yvonne M. Lenighan
Affiliation:
Nutrigenomics Research Group and Institute of Food and Health, University College Dublin, Dublin, Ireland
Elaine B. Kennedy
Affiliation:
Nutrigenomics Research Group and Institute of Food and Health, University College Dublin, Dublin, Ireland
Fiona C. McGillicuddy
Affiliation:
Nutrigenomics Research Group and Institute of Food and Health, University College Dublin, Dublin, Ireland Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland
Paul W. O'Toole
Affiliation:
APC Microbiome Ireland, University College Cork, Cork, Ireland School of Microbiology, University College Cork, Cork, Ireland
Helen M. Roche
Affiliation:
Nutrigenomics Research Group and Institute of Food and Health, University College Dublin, Dublin, Ireland Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland

Abstract

Reduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.


Type
Abstract
Copyright
Copyright © The Authors 2020

References

McGillicuddy, et al. (2011) Diabetes 60(6), 16881698.10.2337/db10-1278CrossRefGoogle Scholar
Henao-Mejia, et al. (2012) Nature 482, 179185.10.1038/nature10809CrossRefGoogle Scholar

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 0
Total number of PDF views: 49 *
View data table for this chart

* Views captured on Cambridge Core between 10th June 2020 - 3rd December 2020. This data will be updated every 24 hours.

Access
Hostname: page-component-79f79cbf67-cxk4b Total loading time: 0.423 Render date: 2020-12-03T02:47:34.615Z Query parameters: { "hasAccess": "1", "openAccess": "0", "isLogged": "0", "lang": "en" } Feature Flags last update: Thu Dec 03 2020 02:06:03 GMT+0000 (Coordinated Universal Time) Feature Flags: { "metrics": true, "metricsAbstractViews": false, "peerReview": true, "crossMark": true, "comments": true, "relatedCommentaries": true, "subject": true, "clr": false, "languageSwitch": true }

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Microbiome transfer between IL-1RI-/- and wild-type mice during high or low-fat feeding alters metabolic tissue functionality but not glucose homeostasis.
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Microbiome transfer between IL-1RI-/- and wild-type mice during high or low-fat feeding alters metabolic tissue functionality but not glucose homeostasis.
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Microbiome transfer between IL-1RI-/- and wild-type mice during high or low-fat feeding alters metabolic tissue functionality but not glucose homeostasis.
Available formats
×
×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *