The development of diet-induced obesity and glucose intolerance in C57BL/6 mice on a high-fat diet consists of distinct phases

Lynda M Williams, Fiona M Campbell, Janice E Drew, Christiane Koch, Nigel Hoggard, William D Rees, Torkamol Kamolrat, Ha Thi Ngo, Inger-Lise Steffensen, Stuart R Gray, Alexander Tups

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Abstract

High-fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.

Original languageEnglish
Article numbere106159
Number of pages19
JournalPloS ONE
Volume9
Issue number8
DOIs
Publication statusPublished - 29 Aug 2014

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Glucose Intolerance
High Fat Diet
high fat diet
Nutrition
Inbred C57BL Mouse
white adipose tissue
obesity
Obesity
Fats
White Adipose Tissue
Diet
Glucose
inflammation
glucose
mice
Acute-Phase Reaction
Inflammation
diet
lipids
adiposity

Keywords

  • induced insulin-resistance
  • apolipoprotein-a-IV
  • metabolic syndrome
  • adipose-tissue
  • IKK-beta
  • inflammation
  • sensitivity
  • homeostasis
  • activation
  • term

Cite this

The development of diet-induced obesity and glucose intolerance in C57BL/6 mice on a high-fat diet consists of distinct phases. / Williams, Lynda M; Campbell, Fiona M; Drew, Janice E; Koch, Christiane; Hoggard, Nigel; Rees, William D; Kamolrat, Torkamol; Thi Ngo, Ha; Steffensen, Inger-Lise; Gray, Stuart R; Tups, Alexander.

In: PloS ONE, Vol. 9, No. 8, e106159, 29.08.2014.

Research output: Contribution to journalArticle

Williams, Lynda M ; Campbell, Fiona M ; Drew, Janice E ; Koch, Christiane ; Hoggard, Nigel ; Rees, William D ; Kamolrat, Torkamol ; Thi Ngo, Ha ; Steffensen, Inger-Lise ; Gray, Stuart R ; Tups, Alexander. / The development of diet-induced obesity and glucose intolerance in C57BL/6 mice on a high-fat diet consists of distinct phases. In: PloS ONE. 2014 ; Vol. 9, No. 8.
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abstract = "High-fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50{\%} increase in area under the curve (AUC) for HF and PF mice, which improved to 30{\%} after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60{\%}, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.",
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note = "Acknowledgments Christine Grant, Gail Hempseed, Amanda C. Morris, Phyllis Nicol, Andrew J. Farquharson and Susan M. Hay, RINH University of Aberdeen are acknowledged for their expert and invaluable technical input. We would also like to thank Biomathematics and Statistics Scotland (BioSS) for expert advice on statistical analysis.",
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T1 - The development of diet-induced obesity and glucose intolerance in C57BL/6 mice on a high-fat diet consists of distinct phases

AU - Williams, Lynda M

AU - Campbell, Fiona M

AU - Drew, Janice E

AU - Koch, Christiane

AU - Hoggard, Nigel

AU - Rees, William D

AU - Kamolrat, Torkamol

AU - Thi Ngo, Ha

AU - Steffensen, Inger-Lise

AU - Gray, Stuart R

AU - Tups, Alexander

N1 - Acknowledgments Christine Grant, Gail Hempseed, Amanda C. Morris, Phyllis Nicol, Andrew J. Farquharson and Susan M. Hay, RINH University of Aberdeen are acknowledged for their expert and invaluable technical input. We would also like to thank Biomathematics and Statistics Scotland (BioSS) for expert advice on statistical analysis.

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Y1 - 2014/8/29

N2 - High-fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.

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KW - induced insulin-resistance

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KW - adipose-tissue

KW - IKK-beta

KW - inflammation

KW - sensitivity

KW - homeostasis

KW - activation

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