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Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice

Fryklund, Claes LU ; Neuhaus, Mathis LU orcid ; Morén, Björn LU orcid ; Borreguero-Muñoz, Andrea LU ; Lundmark, Richard and Stenkula, Karin G. LU (2022) In Frontiers in Cell and Developmental Biology 10.
Abstract

To accommodate surplus energy, the adipose tissue expands by increasing adipocyte size (hypertrophy) and number (hyperplasia). The presence of hypertrophic adipocytes is a key characteristic of adipose tissue dysfunction. High-fat diet (HFD) fed C57BL/6J mice are a commonly used model to study obesity and obesity-related complications. In the present study, we have characterized adipose plasticity, at both the cellular and tissue level, by examining the temporal development of systemic insulin resistance and adiposity in response to HFD-feeding for 4, 8, and 12 weeks (4w, 8w, and 12w). Within the same time frame, we examined systemic metabolic flexibility and adipose plasticity when switching from HFD- to chow-diet during the last 2... (More)

To accommodate surplus energy, the adipose tissue expands by increasing adipocyte size (hypertrophy) and number (hyperplasia). The presence of hypertrophic adipocytes is a key characteristic of adipose tissue dysfunction. High-fat diet (HFD) fed C57BL/6J mice are a commonly used model to study obesity and obesity-related complications. In the present study, we have characterized adipose plasticity, at both the cellular and tissue level, by examining the temporal development of systemic insulin resistance and adiposity in response to HFD-feeding for 4, 8, and 12 weeks (4w, 8w, and 12w). Within the same time frame, we examined systemic metabolic flexibility and adipose plasticity when switching from HFD- to chow-diet during the last 2 weeks of diet intervention (referred to as the reverse (REV) group: 4wREV (2w HFD+2w chow), 8wREV (6w HFD+2w chow), 12wREV (10w HFD+2w chow)). In response to HFD-feeding over time, the 12w group had impaired systemic insulin sensitivity compared to both the 4w and 8w groups, accompanied by an increase in hypertrophic inguinal adipocytes and liver triglycerides. After reversing from HFD- to chow-feeding, most parameters were completely restored to chow control levels for 4wREV and 8wREV groups. In contrast, the 12wREV group had a significantly increased number of hypertrophic adipocytes, liver triglycerides accumulation, and impaired systemic insulin sensitivity compared to chow-fed mice. Further, image analysis at the single-cell level revealed a cell-size dependent organization of actin filaments for all feeding conditions. Indeed, the impaired adipocyte size plasticity in the 12wREV group was accompanied by increased actin filamentation and reduced insulin-stimulated glucose uptake compared with chow-fed mice. In summary, these results demonstrate that the C57BL/6J HFD-feeding model has a large capacity to restore adipocyte cell size and systemic insulin sensitivity, and that a metabolic tipping point occurs between 8 and 12w of HFD-feeding where this plasticity deteriorates. We believe these findings provide substantial understanding of C57BL/6J mice as an obesity model, and that an increased pool of hypertrophic ING adipocytes could contribute to aggravated insulin resistance.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adipocytes, cell size, cytoskeleton, glucose transport, insulin, obesity
in
Frontiers in Cell and Developmental Biology
volume
10
article number
942374
publisher
Frontiers Media S. A.
external identifiers
  • pmid:36158197
  • scopus:85138356642
ISSN
2296-634X
DOI
10.3389/fcell.2022.942374
language
English
LU publication?
yes
additional info
Publisher Copyright: Copyright © 2022 Fryklund, Neuhaus, Morén, Borreguero-Muñoz, Lundmark and Stenkula.
id
b205abb4-fae1-4f72-b0ff-adc98cfd73e1
date added to LUP
2022-12-05 10:35:16
date last changed
2024-06-13 20:52:40
@article{b205abb4-fae1-4f72-b0ff-adc98cfd73e1,
  abstract     = {{<p>To accommodate surplus energy, the adipose tissue expands by increasing adipocyte size (hypertrophy) and number (hyperplasia). The presence of hypertrophic adipocytes is a key characteristic of adipose tissue dysfunction. High-fat diet (HFD) fed C57BL/6J mice are a commonly used model to study obesity and obesity-related complications. In the present study, we have characterized adipose plasticity, at both the cellular and tissue level, by examining the temporal development of systemic insulin resistance and adiposity in response to HFD-feeding for 4, 8, and 12 weeks (4w, 8w, and 12w). Within the same time frame, we examined systemic metabolic flexibility and adipose plasticity when switching from HFD- to chow-diet during the last 2 weeks of diet intervention (referred to as the reverse (REV) group: 4wREV (2w HFD+2w chow), 8wREV (6w HFD+2w chow), 12wREV (10w HFD+2w chow)). In response to HFD-feeding over time, the 12w group had impaired systemic insulin sensitivity compared to both the 4w and 8w groups, accompanied by an increase in hypertrophic inguinal adipocytes and liver triglycerides. After reversing from HFD- to chow-feeding, most parameters were completely restored to chow control levels for 4wREV and 8wREV groups. In contrast, the 12wREV group had a significantly increased number of hypertrophic adipocytes, liver triglycerides accumulation, and impaired systemic insulin sensitivity compared to chow-fed mice. Further, image analysis at the single-cell level revealed a cell-size dependent organization of actin filaments for all feeding conditions. Indeed, the impaired adipocyte size plasticity in the 12wREV group was accompanied by increased actin filamentation and reduced insulin-stimulated glucose uptake compared with chow-fed mice. In summary, these results demonstrate that the C57BL/6J HFD-feeding model has a large capacity to restore adipocyte cell size and systemic insulin sensitivity, and that a metabolic tipping point occurs between 8 and 12w of HFD-feeding where this plasticity deteriorates. We believe these findings provide substantial understanding of C57BL/6J mice as an obesity model, and that an increased pool of hypertrophic ING adipocytes could contribute to aggravated insulin resistance.</p>}},
  author       = {{Fryklund, Claes and Neuhaus, Mathis and Morén, Björn and Borreguero-Muñoz, Andrea and Lundmark, Richard and Stenkula, Karin G.}},
  issn         = {{2296-634X}},
  keywords     = {{adipocytes; cell size; cytoskeleton; glucose transport; insulin; obesity}},
  language     = {{eng}},
  month        = {{09}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Cell and Developmental Biology}},
  title        = {{Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice}},
  url          = {{http://dx.doi.org/10.3389/fcell.2022.942374}},
  doi          = {{10.3389/fcell.2022.942374}},
  volume       = {{10}},
  year         = {{2022}},
}