Adipocyte-specific deletion of IL-6 does not attenuate obesity-induced weight gain or glucose intolerance in mice

Martin Whitham, Martin Pal, Tim Petzold, Marit Hjorth, Casey L. Egan, Julia S. Brunner, Emma Estevez, Peter Iliades, Borivoj Zivanovic, Saskia Reibe, William E. Hughes, Maria Findeisen, Juan Hidalgo, Mark A. Febbraio

Research output: Contribution to journalArticleResearchpeer-review

Abstract

It has been suggested that interleukin-6 (IL-6) produced by adipocytes in obesity leads to liver insulin resistance, although this hypothesis has never been definitively tested. Accordingly, we did so by generating adipocyte-specific IL-6-deficient (AdipoIL-6-/-) mice and studying them in the context of diet-induced and genetic obesity. Mice carrying two floxed alleles of IL-6 (C57Bl/6J) were crossed with Cre recombinase-overexpressing mice driven by the adiponectin promoter to generate AdipoIL-6-/- mice. AdipoIL-6-/- and floxed littermate controls were fed a standard chow or high-fat diet (HFD) for 16 wk and comprehensively metabolically phenotyped. In addition to a diet-induced obesity model, we also examined the role of adipocyte-derived IL-6 in a genetic model of obesity and insulin resistance by crossing the AdipoIL-6-/- mice with leptin-deficient (ob/ob) mice. As expected, mice on HFD and ob/ob mice displayed marked weight gain and increased fat mass compared with chow-fed and ob/+ (littermate control) animals, respectively. However, deletion of IL-6 from adipocytes in either model had no effect on glucose tolerance or fasting hyperinsulinemia. We concluded that adipocyte-specific IL-6 does not contribute to whole body glucose intolerance in obese mice.

Original languageEnglish
Pages (from-to)E597-E604
Number of pages8
JournalAmerican journal of physiology. Endocrinology and metabolism
Volume317
Issue number4
DOIs
Publication statusPublished - 30 Sep 2019

Keywords

  • adiposity
  • floxed
  • glucose tolerance
  • IL-6
  • obesity

Cite this

Whitham, Martin ; Pal, Martin ; Petzold, Tim ; Hjorth, Marit ; Egan, Casey L. ; Brunner, Julia S. ; Estevez, Emma ; Iliades, Peter ; Zivanovic, Borivoj ; Reibe, Saskia ; Hughes, William E. ; Findeisen, Maria ; Hidalgo, Juan ; Febbraio, Mark A. / Adipocyte-specific deletion of IL-6 does not attenuate obesity-induced weight gain or glucose intolerance in mice. In: American journal of physiology. Endocrinology and metabolism. 2019 ; Vol. 317, No. 4. pp. E597-E604.
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abstract = "It has been suggested that interleukin-6 (IL-6) produced by adipocytes in obesity leads to liver insulin resistance, although this hypothesis has never been definitively tested. Accordingly, we did so by generating adipocyte-specific IL-6-deficient (AdipoIL-6-/-) mice and studying them in the context of diet-induced and genetic obesity. Mice carrying two floxed alleles of IL-6 (C57Bl/6J) were crossed with Cre recombinase-overexpressing mice driven by the adiponectin promoter to generate AdipoIL-6-/- mice. AdipoIL-6-/- and floxed littermate controls were fed a standard chow or high-fat diet (HFD) for 16 wk and comprehensively metabolically phenotyped. In addition to a diet-induced obesity model, we also examined the role of adipocyte-derived IL-6 in a genetic model of obesity and insulin resistance by crossing the AdipoIL-6-/- mice with leptin-deficient (ob/ob) mice. As expected, mice on HFD and ob/ob mice displayed marked weight gain and increased fat mass compared with chow-fed and ob/+ (littermate control) animals, respectively. However, deletion of IL-6 from adipocytes in either model had no effect on glucose tolerance or fasting hyperinsulinemia. We concluded that adipocyte-specific IL-6 does not contribute to whole body glucose intolerance in obese mice.",
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author = "Martin Whitham and Martin Pal and Tim Petzold and Marit Hjorth and Egan, {Casey L.} and Brunner, {Julia S.} and Emma Estevez and Peter Iliades and Borivoj Zivanovic and Saskia Reibe and Hughes, {William E.} and Maria Findeisen and Juan Hidalgo and Febbraio, {Mark A.}",
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Whitham, M, Pal, M, Petzold, T, Hjorth, M, Egan, CL, Brunner, JS, Estevez, E, Iliades, P, Zivanovic, B, Reibe, S, Hughes, WE, Findeisen, M, Hidalgo, J & Febbraio, MA 2019, 'Adipocyte-specific deletion of IL-6 does not attenuate obesity-induced weight gain or glucose intolerance in mice', American journal of physiology. Endocrinology and metabolism, vol. 317, no. 4, pp. E597-E604. https://doi.org/10.1152/ajpendo.00206.2019

Adipocyte-specific deletion of IL-6 does not attenuate obesity-induced weight gain or glucose intolerance in mice. / Whitham, Martin; Pal, Martin; Petzold, Tim; Hjorth, Marit; Egan, Casey L.; Brunner, Julia S.; Estevez, Emma; Iliades, Peter; Zivanovic, Borivoj; Reibe, Saskia; Hughes, William E.; Findeisen, Maria; Hidalgo, Juan; Febbraio, Mark A.

In: American journal of physiology. Endocrinology and metabolism, Vol. 317, No. 4, 30.09.2019, p. E597-E604.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Adipocyte-specific deletion of IL-6 does not attenuate obesity-induced weight gain or glucose intolerance in mice

AU - Whitham, Martin

AU - Pal, Martin

AU - Petzold, Tim

AU - Hjorth, Marit

AU - Egan, Casey L.

AU - Brunner, Julia S.

AU - Estevez, Emma

AU - Iliades, Peter

AU - Zivanovic, Borivoj

AU - Reibe, Saskia

AU - Hughes, William E.

AU - Findeisen, Maria

AU - Hidalgo, Juan

AU - Febbraio, Mark A.

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AB - It has been suggested that interleukin-6 (IL-6) produced by adipocytes in obesity leads to liver insulin resistance, although this hypothesis has never been definitively tested. Accordingly, we did so by generating adipocyte-specific IL-6-deficient (AdipoIL-6-/-) mice and studying them in the context of diet-induced and genetic obesity. Mice carrying two floxed alleles of IL-6 (C57Bl/6J) were crossed with Cre recombinase-overexpressing mice driven by the adiponectin promoter to generate AdipoIL-6-/- mice. AdipoIL-6-/- and floxed littermate controls were fed a standard chow or high-fat diet (HFD) for 16 wk and comprehensively metabolically phenotyped. In addition to a diet-induced obesity model, we also examined the role of adipocyte-derived IL-6 in a genetic model of obesity and insulin resistance by crossing the AdipoIL-6-/- mice with leptin-deficient (ob/ob) mice. As expected, mice on HFD and ob/ob mice displayed marked weight gain and increased fat mass compared with chow-fed and ob/+ (littermate control) animals, respectively. However, deletion of IL-6 from adipocytes in either model had no effect on glucose tolerance or fasting hyperinsulinemia. We concluded that adipocyte-specific IL-6 does not contribute to whole body glucose intolerance in obese mice.

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