Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding

Nigel Turner, Grzegorz Kowalski, Simon J Leslie, Steve Risis, Christine Yang, Robert S Lee-Young, Joanne R Babb, Peter J Meikle, Graeme I Lancaster, Darren Colin Henstridge, Phillip J White, Edward W Kraegen, A Marette, Gregory J Cooney, Mark Anthony Febbraio, Clinton Bruce

Research output: Contribution to journalArticleResearchpeer-review

182 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: While it is well known that diet-induced obesity causes insulin resistance, the precise mechanisms underpinning the initiation of insulin resistance are unclear. To determine factors that may cause insulin resistance, we have performed a detailed time-course study in mice fed a high-fat diet (HFD). METHODS: C57Bl/6 mice were fed chow or an HFD from 3 days to 16 weeks and glucose tolerance and tissue-specific insulin action were determined. Tissue lipid profiles were analysed by mass spectrometry and inflammatory markers were measured in adipose tissue, liver and skeletal muscle. RESULTS: Glucose intolerance developed within 3 days of the HFD and did not deteriorate further in the period to 12 weeks. Whole-body insulin resistance, measured by hyperinsulinaemic-euglycaemic clamp, was detected after 1 week of HFD and was due to hepatic insulin resistance. Adipose tissue was insulin resistant after 1 week, while skeletal muscle displayed insulin resistance at 3 weeks, coinciding with a defect in glucose disposal. Interestingly, no further deterioration in insulin sensitivity was observed in any tissue after this initial defect. Diacylglycerol content was increased in liver and muscle when insulin resistance first developed, while the onset of insulin resistance in adipose tissue was associated with increases in ceramide and sphingomyelin. Adipose tissue inflammation was only detected at 16 weeks of HFD and did not correlate with the induction of insulin resistance. CONCLUSIONS/INTERPRETATION: HFD-induced whole-body insulin resistance is initiated by impaired hepatic insulin action and exacerbated by skeletal muscle insulin resistance and is associated with the accumulation of specific bioactive lipid species.
Original languageEnglish
Pages (from-to)1638 - 1648
Number of pages11
JournalDiabetologia
Volume56
Issue number7
DOIs
Publication statusPublished - 2013

Cite this

Turner, N., Kowalski, G., Leslie, S. J., Risis, S., Yang, C., Lee-Young, R. S., ... Bruce, C. (2013). Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding. Diabetologia, 56(7), 1638 - 1648. https://doi.org/10.1007/s00125-013-2913-1
Turner, Nigel ; Kowalski, Grzegorz ; Leslie, Simon J ; Risis, Steve ; Yang, Christine ; Lee-Young, Robert S ; Babb, Joanne R ; Meikle, Peter J ; Lancaster, Graeme I ; Henstridge, Darren Colin ; White, Phillip J ; Kraegen, Edward W ; Marette, A ; Cooney, Gregory J ; Febbraio, Mark Anthony ; Bruce, Clinton. / Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding. In: Diabetologia. 2013 ; Vol. 56, No. 7. pp. 1638 - 1648.
@article{ea6d0d0be47b4b9ba4c84427e1bb6810,
title = "Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding",
abstract = "AIMS/HYPOTHESIS: While it is well known that diet-induced obesity causes insulin resistance, the precise mechanisms underpinning the initiation of insulin resistance are unclear. To determine factors that may cause insulin resistance, we have performed a detailed time-course study in mice fed a high-fat diet (HFD). METHODS: C57Bl/6 mice were fed chow or an HFD from 3 days to 16 weeks and glucose tolerance and tissue-specific insulin action were determined. Tissue lipid profiles were analysed by mass spectrometry and inflammatory markers were measured in adipose tissue, liver and skeletal muscle. RESULTS: Glucose intolerance developed within 3 days of the HFD and did not deteriorate further in the period to 12 weeks. Whole-body insulin resistance, measured by hyperinsulinaemic-euglycaemic clamp, was detected after 1 week of HFD and was due to hepatic insulin resistance. Adipose tissue was insulin resistant after 1 week, while skeletal muscle displayed insulin resistance at 3 weeks, coinciding with a defect in glucose disposal. Interestingly, no further deterioration in insulin sensitivity was observed in any tissue after this initial defect. Diacylglycerol content was increased in liver and muscle when insulin resistance first developed, while the onset of insulin resistance in adipose tissue was associated with increases in ceramide and sphingomyelin. Adipose tissue inflammation was only detected at 16 weeks of HFD and did not correlate with the induction of insulin resistance. CONCLUSIONS/INTERPRETATION: HFD-induced whole-body insulin resistance is initiated by impaired hepatic insulin action and exacerbated by skeletal muscle insulin resistance and is associated with the accumulation of specific bioactive lipid species.",
author = "Nigel Turner and Grzegorz Kowalski and Leslie, {Simon J} and Steve Risis and Christine Yang and Lee-Young, {Robert S} and Babb, {Joanne R} and Meikle, {Peter J} and Lancaster, {Graeme I} and Henstridge, {Darren Colin} and White, {Phillip J} and Kraegen, {Edward W} and A Marette and Cooney, {Gregory J} and Febbraio, {Mark Anthony} and Clinton Bruce",
year = "2013",
doi = "10.1007/s00125-013-2913-1",
language = "English",
volume = "56",
pages = "1638 -- 1648",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer-Verlag London Ltd.",
number = "7",

}

Turner, N, Kowalski, G, Leslie, SJ, Risis, S, Yang, C, Lee-Young, RS, Babb, JR, Meikle, PJ, Lancaster, GI, Henstridge, DC, White, PJ, Kraegen, EW, Marette, A, Cooney, GJ, Febbraio, MA & Bruce, C 2013, 'Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding', Diabetologia, vol. 56, no. 7, pp. 1638 - 1648. https://doi.org/10.1007/s00125-013-2913-1

Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding. / Turner, Nigel; Kowalski, Grzegorz; Leslie, Simon J; Risis, Steve; Yang, Christine; Lee-Young, Robert S; Babb, Joanne R; Meikle, Peter J; Lancaster, Graeme I; Henstridge, Darren Colin; White, Phillip J; Kraegen, Edward W; Marette, A; Cooney, Gregory J; Febbraio, Mark Anthony; Bruce, Clinton.

In: Diabetologia, Vol. 56, No. 7, 2013, p. 1638 - 1648.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding

AU - Turner, Nigel

AU - Kowalski, Grzegorz

AU - Leslie, Simon J

AU - Risis, Steve

AU - Yang, Christine

AU - Lee-Young, Robert S

AU - Babb, Joanne R

AU - Meikle, Peter J

AU - Lancaster, Graeme I

AU - Henstridge, Darren Colin

AU - White, Phillip J

AU - Kraegen, Edward W

AU - Marette, A

AU - Cooney, Gregory J

AU - Febbraio, Mark Anthony

AU - Bruce, Clinton

PY - 2013

Y1 - 2013

N2 - AIMS/HYPOTHESIS: While it is well known that diet-induced obesity causes insulin resistance, the precise mechanisms underpinning the initiation of insulin resistance are unclear. To determine factors that may cause insulin resistance, we have performed a detailed time-course study in mice fed a high-fat diet (HFD). METHODS: C57Bl/6 mice were fed chow or an HFD from 3 days to 16 weeks and glucose tolerance and tissue-specific insulin action were determined. Tissue lipid profiles were analysed by mass spectrometry and inflammatory markers were measured in adipose tissue, liver and skeletal muscle. RESULTS: Glucose intolerance developed within 3 days of the HFD and did not deteriorate further in the period to 12 weeks. Whole-body insulin resistance, measured by hyperinsulinaemic-euglycaemic clamp, was detected after 1 week of HFD and was due to hepatic insulin resistance. Adipose tissue was insulin resistant after 1 week, while skeletal muscle displayed insulin resistance at 3 weeks, coinciding with a defect in glucose disposal. Interestingly, no further deterioration in insulin sensitivity was observed in any tissue after this initial defect. Diacylglycerol content was increased in liver and muscle when insulin resistance first developed, while the onset of insulin resistance in adipose tissue was associated with increases in ceramide and sphingomyelin. Adipose tissue inflammation was only detected at 16 weeks of HFD and did not correlate with the induction of insulin resistance. CONCLUSIONS/INTERPRETATION: HFD-induced whole-body insulin resistance is initiated by impaired hepatic insulin action and exacerbated by skeletal muscle insulin resistance and is associated with the accumulation of specific bioactive lipid species.

AB - AIMS/HYPOTHESIS: While it is well known that diet-induced obesity causes insulin resistance, the precise mechanisms underpinning the initiation of insulin resistance are unclear. To determine factors that may cause insulin resistance, we have performed a detailed time-course study in mice fed a high-fat diet (HFD). METHODS: C57Bl/6 mice were fed chow or an HFD from 3 days to 16 weeks and glucose tolerance and tissue-specific insulin action were determined. Tissue lipid profiles were analysed by mass spectrometry and inflammatory markers were measured in adipose tissue, liver and skeletal muscle. RESULTS: Glucose intolerance developed within 3 days of the HFD and did not deteriorate further in the period to 12 weeks. Whole-body insulin resistance, measured by hyperinsulinaemic-euglycaemic clamp, was detected after 1 week of HFD and was due to hepatic insulin resistance. Adipose tissue was insulin resistant after 1 week, while skeletal muscle displayed insulin resistance at 3 weeks, coinciding with a defect in glucose disposal. Interestingly, no further deterioration in insulin sensitivity was observed in any tissue after this initial defect. Diacylglycerol content was increased in liver and muscle when insulin resistance first developed, while the onset of insulin resistance in adipose tissue was associated with increases in ceramide and sphingomyelin. Adipose tissue inflammation was only detected at 16 weeks of HFD and did not correlate with the induction of insulin resistance. CONCLUSIONS/INTERPRETATION: HFD-induced whole-body insulin resistance is initiated by impaired hepatic insulin action and exacerbated by skeletal muscle insulin resistance and is associated with the accumulation of specific bioactive lipid species.

UR - http://goo.gl/nDTVnH

U2 - 10.1007/s00125-013-2913-1

DO - 10.1007/s00125-013-2913-1

M3 - Article

VL - 56

SP - 1638

EP - 1648

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 7

ER -