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Intact glucose uptake despite deteriorating signaling in adipocytes with high-fat feeding

Hansson, Björn LU ; Wasserstrom, Sebastian LU ; Morén, Björn LU ; Periwal, Vipul; Vikman, Petter LU ; Cushman, Samuel W.; Göransson, Olga LU ; Storm, Petter LU and Stenkula, Karin G. LU (2018) In Journal of Molecular Endocrinology 60(3). p.199-211
Abstract

To capture immediate cellular changes during diet-induced expansion of adipocyte cell volume and number, we characterized mature adipocytes during a short-term high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size distribution analysis using coulter counting. Insulin response in isolated adipocytes was monitored by glucose uptake assay and Western blotting, and confocal microscopy was used to assess autophagic activity. Switching to HFD was accompanied by an immediate adipocyte size expansion and onset of systemic insulin resistance already after two... (More)

To capture immediate cellular changes during diet-induced expansion of adipocyte cell volume and number, we characterized mature adipocytes during a short-term high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size distribution analysis using coulter counting. Insulin response in isolated adipocytes was monitored by glucose uptake assay and Western blotting, and confocal microscopy was used to assess autophagic activity. Switching to HFD was accompanied by an immediate adipocyte size expansion and onset of systemic insulin resistance already after two days, followed by recruitment of new adipocytes. Despite an initially increased non-stimulated and preserved insulin-stimulated glucose uptake, we observed a decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and protein kinase B (PKB). After 14 days of HFD, both the insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160) and glucose uptake was blunted. RNA-seq analysis of adipose tissue revealed transient changes in gene expression at day four, including highly significant upregulation of Trp53inp, previously demonstrated to be involved in autophagy. We confirmed increased autophagy, measured as an increased density of LC3-positive puncta and decreased p62 expression after 14 days of HFD. In conclusion, HFD rapidly induced systemic insulin resistance, whereas insulin-stimulated glucose uptake remained intact throughout 6 days of HFD feeding. We also identified autophagy as an early cellular process that potentially influences adipocyte function upon switching to HFD.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adipocytes, Autophagy, Glucose uptake, Insulin signaling
in
Journal of Molecular Endocrinology
volume
60
issue
3
pages
13 pages
publisher
Society for Endocrinology
external identifiers
  • scopus:85045746910
ISSN
0952-5041
DOI
10.1530/JME-17-0195
language
English
LU publication?
yes
id
d87e542a-d47d-430d-9772-a3ab749ba139
date added to LUP
2018-05-23 10:39:10
date last changed
2019-02-20 11:17:43
@article{d87e542a-d47d-430d-9772-a3ab749ba139,
  abstract     = {<p>To capture immediate cellular changes during diet-induced expansion of adipocyte cell volume and number, we characterized mature adipocytes during a short-term high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size distribution analysis using coulter counting. Insulin response in isolated adipocytes was monitored by glucose uptake assay and Western blotting, and confocal microscopy was used to assess autophagic activity. Switching to HFD was accompanied by an immediate adipocyte size expansion and onset of systemic insulin resistance already after two days, followed by recruitment of new adipocytes. Despite an initially increased non-stimulated and preserved insulin-stimulated glucose uptake, we observed a decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and protein kinase B (PKB). After 14 days of HFD, both the insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160) and glucose uptake was blunted. RNA-seq analysis of adipose tissue revealed transient changes in gene expression at day four, including highly significant upregulation of Trp53inp, previously demonstrated to be involved in autophagy. We confirmed increased autophagy, measured as an increased density of LC3-positive puncta and decreased p62 expression after 14 days of HFD. In conclusion, HFD rapidly induced systemic insulin resistance, whereas insulin-stimulated glucose uptake remained intact throughout 6 days of HFD feeding. We also identified autophagy as an early cellular process that potentially influences adipocyte function upon switching to HFD.</p>},
  author       = {Hansson, Björn and Wasserstrom, Sebastian and Morén, Björn and Periwal, Vipul and Vikman, Petter and Cushman, Samuel W. and Göransson, Olga and Storm, Petter and Stenkula, Karin G.},
  issn         = {0952-5041},
  keyword      = {Adipocytes,Autophagy,Glucose uptake,Insulin signaling},
  language     = {eng},
  month        = {04},
  number       = {3},
  pages        = {199--211},
  publisher    = {Society for Endocrinology},
  series       = {Journal of Molecular Endocrinology},
  title        = {Intact glucose uptake despite deteriorating signaling in adipocytes with high-fat feeding},
  url          = {http://dx.doi.org/10.1530/JME-17-0195},
  volume       = {60},
  year         = {2018},
}