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

doi:10.1152/ajpendo.00206.2019

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

Sport, Exercise and Rehabilitation Sciences

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Abstract

OBJECTIVES: 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.

METHODS: Mice carrying 2 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 (FL) were fed a standard chow (CHOW) or high fat diet (HFD) for 16 weeks and comprehensively metabolically phenotyped. In addition to a diet-induced obesity (DIO) 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.

RESULTS: As expected, mice on a 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.

CONCLUSION: Adipocyte specific IL-6 does not contribute to whole body glucose intolerance in obese mice.

Original language	English
Pages (from-to)	E597-E604
Number of pages	8
Journal	American Journal of Physiology - Endocrinology and Metabolism
Volume	317
Issue number	4
Early online date	6 Aug 2019
DOIs	https://doi.org/10.1152/ajpendo.00206.2019
Publication status	Published - 1 Oct 2019

Keywords

Glucose tolerance
Adiposity
Floxed
IL6
Obesity
adiposity
floxed
glucose tolerance
IL-6
obesity

ASJC Scopus subject areas

Physiology (medical)
Physiology
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1152/ajpendo.00206.2019Licence: None: All rights reserved

Whitham_et_al_Adipocyte_specific_deletion_of_IL-6_American_Journal_of_Physiology-_Endocrinology_and_Metabolism_2019
Whitham et al (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 https://doi.org/10.1152/ajpendo.00206.2019
Accepted author manuscript, 6.22 MBLicence: None: All rights reserved

https://www.physiology.org/doi/abs/10.1152/ajpendo.00206.2019Licence: None: All rights reserved

Cite this

Whitham, M., Pal, M., Petzold, T., Hjorth, M., Egan, C. L., Brunner, J. S., Estevez, E., Iliades, P., Zivanovic, B., Reibe, S., Hughes, W. E., Findeisen, M., Hidalgo, J., & Febbraio, M. A. (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, 317(4), E597-E604. Advance online publication. https://doi.org/10.1152/ajpendo.00206.2019

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

abstract = "OBJECTIVES: 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.METHODS: Mice carrying 2 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 (FL) were fed a standard chow (CHOW) or high fat diet (HFD) for 16 weeks and comprehensively metabolically phenotyped. In addition to a diet-induced obesity (DIO) 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.RESULTS: As expected, mice on a 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.CONCLUSION: Adipocyte specific IL-6 does not contribute to whole body glucose intolerance in obese mice.",

keywords = "Glucose tolerance, Adiposity, Floxed, IL6, Obesity, adiposity, floxed, glucose tolerance, IL-6, obesity",

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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language = "English",

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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

TY - JOUR

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

PY - 2019/10/1

Y1 - 2019/10/1

N2 - OBJECTIVES: 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.METHODS: Mice carrying 2 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 (FL) were fed a standard chow (CHOW) or high fat diet (HFD) for 16 weeks and comprehensively metabolically phenotyped. In addition to a diet-induced obesity (DIO) 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.RESULTS: As expected, mice on a 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.CONCLUSION: Adipocyte specific IL-6 does not contribute to whole body glucose intolerance in obese mice.

AB - OBJECTIVES: 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.METHODS: Mice carrying 2 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 (FL) were fed a standard chow (CHOW) or high fat diet (HFD) for 16 weeks and comprehensively metabolically phenotyped. In addition to a diet-induced obesity (DIO) 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.RESULTS: As expected, mice on a 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.CONCLUSION: Adipocyte specific IL-6 does not contribute to whole body glucose intolerance in obese mice.

KW - Glucose tolerance

KW - Adiposity

KW - Floxed

KW - IL6

KW - Obesity

KW - adiposity

KW - floxed

KW - glucose tolerance

KW - IL-6

KW - obesity

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U2 - 10.1152/ajpendo.00206.2019

DO - 10.1152/ajpendo.00206.2019

M3 - Article

C2 - 31386565

SN - 0193-1849

VL - 317

SP - E597-E604

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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