Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice

Samantha L. Hocking; Rebecca L. Stewart; Amanda E. Brandon; Eurwin Suryana; Ella Stuart; Emily M. Baldwin; Ganesh A. Kolumam; Zora Modrusan; Jagath R. Junutula; Jenny E. Gunton; Michael Medynskyj; Sinead P. Blaber; Elisabeth Karsten; Benjamin R. Herbert; David E. James; Gregory J. Cooney; Michael M. Swarbrick

doi:10.1007/s00125-015-3583-y

Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice

Samantha L. Hocking, Rebecca L. Stewart, Amanda E. Brandon, Eurwin Suryana, Ella Stuart, Emily M. Baldwin, Ganesh A. Kolumam, Zora Modrusan, Jagath R. Junutula, Jenny E. Gunton, Michael Medynskyj, Sinead P. Blaber, Elisabeth Karsten, Benjamin R. Herbert, David E. James, Gregory J. Cooney, Michael M. Swarbrick^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

54 Citations (Scopus)

Abstract

Aims/hypothesis Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood.

Methods We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks.

Results Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [ΜIP-1β]), compared with sham-operated mice. Plasma IL-17 and MIP-1β concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n = 40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations.

Conclusions/interpretation Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice.

Original language	English
Pages (from-to)	1587-1600
Number of pages	14
Journal	Diabetologia
Volume	58
Issue number	7
DOIs	https://doi.org/10.1007/s00125-015-3583-y
Publication status	Published - Jul 2015

Keywords

Adipose tissue
Body fat distribution
Fatty liver
Glucose intolerance
Inflammation
Insulin resistance
Intra-abdominal fat
Obesity
Subcutaneous fat
Visceral

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10.1007/s00125-015-3583-y

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Hocking, S. L., Stewart, R. L., Brandon, A. E., Suryana, E., Stuart, E., Baldwin, E. M., Kolumam, G. A., Modrusan, Z., Junutula, J. R., Gunton, J. E., Medynskyj, M., Blaber, S. P., Karsten, E., Herbert, B. R., James, D. E., Cooney, G. J., & Swarbrick, M. M. (2015). Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice. Diabetologia, 58(7), 1587-1600. https://doi.org/10.1007/s00125-015-3583-y

Hocking, Samantha L. ; Stewart, Rebecca L. ; Brandon, Amanda E. ; Suryana, Eurwin ; Stuart, Ella ; Baldwin, Emily M. ; Kolumam, Ganesh A. ; Modrusan, Zora ; Junutula, Jagath R. ; Gunton, Jenny E. ; Medynskyj, Michael ; Blaber, Sinead P. ; Karsten, Elisabeth ; Herbert, Benjamin R. ; James, David E. ; Cooney, Gregory J. ; Swarbrick, Michael M. / Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice. In: Diabetologia. 2015 ; Vol. 58, No. 7. pp. 1587-1600.

@article{3673bdaed36048bd9eb21bc8352a858d,

title = "Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice",

abstract = "Aims/hypothesis Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood. Methods We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks. Results Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [ΜIP-1β]), compared with sham-operated mice. Plasma IL-17 and MIP-1β concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n = 40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations. Conclusions/interpretation Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice.",

keywords = "Adipose tissue, Body fat distribution, Fatty liver, Glucose intolerance, Inflammation, Insulin resistance, Intra-abdominal fat, Obesity, Subcutaneous fat, Visceral",

author = "Hocking, {Samantha L.} and Stewart, {Rebecca L.} and Brandon, {Amanda E.} and Eurwin Suryana and Ella Stuart and Baldwin, {Emily M.} and Kolumam, {Ganesh A.} and Zora Modrusan and Junutula, {Jagath R.} and Gunton, {Jenny E.} and Michael Medynskyj and Blaber, {Sinead P.} and Elisabeth Karsten and Herbert, {Benjamin R.} and James, {David E.} and Cooney, {Gregory J.} and Swarbrick, {Michael M.}",

year = "2015",

month = jul,

doi = "10.1007/s00125-015-3583-y",

language = "English",

volume = "58",

pages = "1587--1600",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer, Springer Nature",

number = "7",

}

Hocking, SL, Stewart, RL, Brandon, AE, Suryana, E, Stuart, E, Baldwin, EM, Kolumam, GA, Modrusan, Z, Junutula, JR, Gunton, JE, Medynskyj, M, Blaber, SP, Karsten, E, Herbert, BR, James, DE, Cooney, GJ & Swarbrick, MM 2015, 'Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice', Diabetologia, vol. 58, no. 7, pp. 1587-1600. https://doi.org/10.1007/s00125-015-3583-y

Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice. / Hocking, Samantha L.; Stewart, Rebecca L.; Brandon, Amanda E.; Suryana, Eurwin; Stuart, Ella; Baldwin, Emily M.; Kolumam, Ganesh A.; Modrusan, Zora; Junutula, Jagath R.; Gunton, Jenny E.; Medynskyj, Michael; Blaber, Sinead P.; Karsten, Elisabeth; Herbert, Benjamin R.; James, David E.; Cooney, Gregory J.; Swarbrick, Michael M.

In: Diabetologia, Vol. 58, No. 7, 07.2015, p. 1587-1600.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice

AU - Hocking, Samantha L.

AU - Stewart, Rebecca L.

AU - Brandon, Amanda E.

AU - Suryana, Eurwin

AU - Stuart, Ella

AU - Baldwin, Emily M.

AU - Kolumam, Ganesh A.

AU - Modrusan, Zora

AU - Junutula, Jagath R.

AU - Gunton, Jenny E.

AU - Medynskyj, Michael

AU - Blaber, Sinead P.

AU - Karsten, Elisabeth

AU - Herbert, Benjamin R.

AU - James, David E.

AU - Cooney, Gregory J.

AU - Swarbrick, Michael M.

PY - 2015/7

Y1 - 2015/7

N2 - Aims/hypothesis Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood. Methods We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks. Results Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [ΜIP-1β]), compared with sham-operated mice. Plasma IL-17 and MIP-1β concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n = 40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations. Conclusions/interpretation Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice.

AB - Aims/hypothesis Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood. Methods We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks. Results Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [ΜIP-1β]), compared with sham-operated mice. Plasma IL-17 and MIP-1β concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n = 40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations. Conclusions/interpretation Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice.

KW - Adipose tissue

KW - Body fat distribution

KW - Fatty liver

KW - Glucose intolerance

KW - Inflammation

KW - Insulin resistance

KW - Intra-abdominal fat

KW - Obesity

KW - Subcutaneous fat

KW - Visceral

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U2 - 10.1007/s00125-015-3583-y

DO - 10.1007/s00125-015-3583-y

M3 - Article

C2 - 25899451

AN - SCOPUS:84931577296

VL - 58

SP - 1587

EP - 1600

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 7

ER -

Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice

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