Cargando…
Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice
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 obesi...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489915/ https://www.ncbi.nlm.nih.gov/pubmed/36158197 http://dx.doi.org/10.3389/fcell.2022.942374 |
_version_ | 1784792973056147456 |
---|---|
author | Fryklund, Claes Neuhaus, Mathis Morén, Björn Borreguero-Muñoz, Andrea Lundmark, Richard Stenkula, Karin G. |
author_facet | Fryklund, Claes Neuhaus, Mathis Morén, Björn Borreguero-Muñoz, Andrea Lundmark, Richard Stenkula, Karin G. |
author_sort | Fryklund, Claes |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9489915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94899152022-09-22 Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice Fryklund, Claes Neuhaus, Mathis Morén, Björn Borreguero-Muñoz, Andrea Lundmark, Richard Stenkula, Karin G. Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2022-09-07 /pmc/articles/PMC9489915/ /pubmed/36158197 http://dx.doi.org/10.3389/fcell.2022.942374 Text en Copyright © 2022 Fryklund, Neuhaus, Morén, Borreguero-Muñoz, Lundmark and Stenkula. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Fryklund, Claes Neuhaus, Mathis Morén, Björn Borreguero-Muñoz, Andrea Lundmark, Richard Stenkula, Karin G. Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice |
title | Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice |
title_full | Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice |
title_fullStr | Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice |
title_full_unstemmed | Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice |
title_short | Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice |
title_sort | expansion of the inguinal adipose tissue depot correlates with systemic insulin resistance in c57bl/6j mice |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489915/ https://www.ncbi.nlm.nih.gov/pubmed/36158197 http://dx.doi.org/10.3389/fcell.2022.942374 |
work_keys_str_mv | AT fryklundclaes expansionoftheinguinaladiposetissuedepotcorrelateswithsystemicinsulinresistanceinc57bl6jmice AT neuhausmathis expansionoftheinguinaladiposetissuedepotcorrelateswithsystemicinsulinresistanceinc57bl6jmice AT morenbjorn expansionoftheinguinaladiposetissuedepotcorrelateswithsystemicinsulinresistanceinc57bl6jmice AT borregueromunozandrea expansionoftheinguinaladiposetissuedepotcorrelateswithsystemicinsulinresistanceinc57bl6jmice AT lundmarkrichard expansionoftheinguinaladiposetissuedepotcorrelateswithsystemicinsulinresistanceinc57bl6jmice AT stenkulakaring expansionoftheinguinaladiposetissuedepotcorrelateswithsystemicinsulinresistanceinc57bl6jmice |