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High-fat diet-induced obesity displays altered adipocyte differentiation in the absence of Interleukin-1 Receptor I (IL-1RI)

Published online by Cambridge University Press:  05 October 2018

K.A.J. Mitchelson ,
J.C. Ralston ,
C.R. Strain ,
Y.M. Lenighan ,
E.B. Kennedy ,
G.M. Lynch ,
F.C. McGillicuddy ,
P.W. O'Toole  and
H.M. Roche
K.A.J. Mitchelson
Affiliation:
Conway Institute of Biomedical and Biomolecular Research and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland
J.C. Ralston
Affiliation:
Conway Institute of Biomedical and Biomolecular Research and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland
C.R. Strain
Affiliation:
Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
Y.M. Lenighan
Affiliation:
Conway Institute of Biomedical and Biomolecular Research and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland
E.B. Kennedy
Affiliation:
Conway Institute of Biomedical and Biomolecular Research and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland
G.M. Lynch
Affiliation:
Conway Institute of Biomedical and Biomolecular Research and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland
F.C. McGillicuddy
Affiliation:
Conway Institute of Biomedical and Biomolecular Research and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland
P.W. O'Toole
Affiliation:
School of Microbiology, University College Cork, Cork, Ireland.
H.M. Roche
Affiliation:
Conway Institute of Biomedical and Biomolecular Research and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland
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Abstract

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Abstract
Information
Proceedings of the Nutrition Society , Volume 77 , Issue OCE4: Summer Meeting, 10–12 July 2018, Getting energy balance right , 2018 , E234
Copyright
Copyright © The Authors 2018 

High-fat diet (HFD)-induced obesity is associated with chronic low grade inflammation within adipose tissue where proinflammatory interleukin 1β (IL1β) expression is present(Reference Herder, Dalmas and Böni-Schnetzler1). Absence of IL-1 Receptor (IL-1RI-/-) protects against high-fat diet (HFD)-induced insulin resistance after 3 months HFD(Reference McGillicuddy, Harford and Reynolds2), but this protection was lost after 6 months HFD(Reference McGillicuddy, Reynolds and Finucane3). Wildtype (WT) mice were more glucose tolerant and insulin sensitive then IL-1RI-/- mice following 6 months HFD. Also, IL-1RI-/- mice showed a loss in adipose functionality, increased adipocyte hypertrophy and reduction in TNFα and IL-6 secretion from stromal vascular fraction (SVF). It was unknown if/how lack of IL-1RI disrupted pre-adipocyte differentiation. Additionally, it has been suggested that microbiome transfer can affect weight gain and phenotype in in mice with inflammation-induced disease. The purpose of this study was to determine how lack of IL-1RI altered adipogenetic potential and adipokine secretion in adipose tissue.

WT and IL-1R-/- mice were fed a HFD for 6 months (45 % kcal). A subset of cages cohoused WT and IL-1R-/- mice to determine whether microbiome transfer can affect phenotype. Glucose tolerance (1·5 g/kg) and insulin tolerance (0·5 U/kg) were tested. We investigated PPAR-γ and FASN gene expression in preadipocytes and differentiated adipocytes, lipogenesis in preadipocytes and differentiated adipocytes and IL-6 secretion in adipose tissue organ culture in wildtype versus IL-1RI-/-. Pre-adipocytes were isolated and differentiated from adipose tissue. Adipogenic marker expression was measured by real time PCR. Oil Red O absorbance measured triacylglycerol (TAG) accumulation. IL-6 secretion from adipose tissue (AT) explants following IL-1β/TNFα stimulation was measured by ELISA. Statistical significance was determined through one – and two-way ANOVA for PCR and GTT/ ITT respectively and unpaired t-test for TAG accumulation.

IL-1RI-/- mice had increased body weight (P ⩽ 0·05) and AT weight compared to WT but both groups had similar glucose tolerance. IL-1RI-/- had higher insulin resistance but this was not statistically significant. Higher glucose tolerance was seen in both IL-1RI-/- and WT mice when they were cohoused together. Analysis of adipogenesis showed Fasn expression was 11- fold higher in differentiated adipocytes from IL-1RI-/- mice compared to WT mice. Conversely, Ppar- γ expression was 37- fold higher in differentiated adipocytes from WT mice compared to IL-1RI-/- mice. TAG accumulation was 50 % lower in differentiated adipocytes from IL-1RI-/- compared to WT. Adipose tissue explants had higher IL-6 secretion from WT then IL-1RI-/-. The microbiomes impact was determined and will be presented. IL-1RI-/- mice may have an increase in AT weight but adipocyte differentiation is impaired and Il-6 secretion is lower. The number of mature adipocytes and their affiliated inflammation is decreased. IL-1RI-/- may protect from HFD induced inflammation through disruption of adipogenesis. Co-housed mice total weight gain indicates a microbiome transfer which could provide a mechanism linking the beneficial alteration to adipogenesis and reduction of inflammation with a decrease in amount of adipose tissue.

This programme was primarily supported by the Irish Department of Agriculture, Food and Marine ‘ImmunoMet’ (Grant number: 14/F/828) programme. HMR is also the recipient of SFI principal investigator award (11/PI/1119) and the Joint Programming Healthy Life for a Healthy Diet (JPI HDHL) funded EU Food Biomarkers Alliance ‘FOODBALL’ (14/JP-HDHL/B3076).

References

1.Herder, C, Dalmas, E, Böni-Schnetzler, M et al. (2015) Trends in Endocrinology & Meabolism 26, 551–563.Google Scholar
2.McGillicuddy, FC, Harford, KA, Reynolds, CM et al. (2011) Diabetes 60, 1688–1698.Google Scholar
3.McGillicuddy, FC, Reynolds, CM, Finucane, et al. (2013) Am J Physiol Endocrinol Metab 305, E834–E844.Google Scholar