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Decrement in resting and insulin-stimulated soleus muscle mitochondrial respiration is an early event in diet-induced obesity in mice

Brunetta, Henver Simionato ; de Paula, Gabriela Cristina LU ; de Oliveira, Jade ; Martins, Eduarda Lopes ; dos Santos, Gustavo Jorge ; Galina, Antonio ; Rafacho, Alex ; de Bem, Andreza Fabro and Nunes, Everson Araújo (2019) In Experimental Physiology 104(3). p.306-321
Abstract

New Findings: What is the central question of this study? What are the temporal responses of mitochondrial respiration and mitochondrial responsivity to insulin in soleus muscle fibres from mice during the development of obesity and insulin resistance? What is the main finding and its importance? Short- and long-term feeding with a high-fat diet markedly reduced soleus mitochondrial respiration and mitochondrial responsivity to insulin before any change in glycogen synthesis. Muscle glycogen synthesis and whole-body insulin resistance were present after 14 and 28 days, respectively. Our findings highlight the plasticity of mitochondria during the development of obesity and insulin resistance. Abstract: Recently, significant attention... (More)

New Findings: What is the central question of this study? What are the temporal responses of mitochondrial respiration and mitochondrial responsivity to insulin in soleus muscle fibres from mice during the development of obesity and insulin resistance? What is the main finding and its importance? Short- and long-term feeding with a high-fat diet markedly reduced soleus mitochondrial respiration and mitochondrial responsivity to insulin before any change in glycogen synthesis. Muscle glycogen synthesis and whole-body insulin resistance were present after 14 and 28 days, respectively. Our findings highlight the plasticity of mitochondria during the development of obesity and insulin resistance. Abstract: Recently, significant attention has been given to the role of muscle mitochondrial function in the development of insulin resistance associated with obesity. Our aim was to investigate temporal alterations in mitochondrial respiration, H2O2 emission and mitochondrial responsivity to insulin in permeabilized skeletal muscle fibres during the development of obesity in mice. Male Swiss mice (5–6 weeks old) were fed with a high-fat diet (60% calories from fat) or standard diet for 7, 14 or 28 days to induce obesity and insulin resistance. Diet-induced obese (DIO) mice presented with reduced glucose tolerance and hyperinsulinaemia after 7 days of high-fat diet. After 14 days, the expected increase in muscle glycogen content after systemic injection of glucose and insulin was not observed in DIO mice. At 28 days, blood glucose decay after insulin injection was significantly impaired. Complex I (pyruvate + malate) and II (succinate)-linked respiration and oxidative phosphorylation (ADP) were decreased after 7 days of high-fat diet and remained low in DIO mice after 14 and 28 days of treatment. Moreover, mitochondria from DIO mice were incapable of increasing respiratory coupling and ADP responsivity after insulin stimulation in all observed periods. Markers of mitochondrial content were reduced only after 28 days of treatment. The mitochondrial H2O2 emission profile varied during the time course of DIO, with a reduction of H2O2 emission in the early stages of DIO and an increased emission after 28 days of treatment. Our data demonstrate that DIO promotes transitory alterations in mitochondrial physiology during the early and late stages of insulin resistance related to obesity.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
diet-induced obesity, insulin resistance, mitochondrial function
in
Experimental Physiology
volume
104
issue
3
pages
306 - 321
publisher
Wiley-Blackwell
external identifiers
  • scopus:85060652551
  • pmid:30578638
ISSN
0958-0670
DOI
10.1113/EP087317
language
English
LU publication?
no
additional info
Funding Information: National Council for Scientific and Technological Development (CNPq) grant numbers 304274/2014-3 and 302692/2016-9. A.F.B., A.G., A.R. and E.A.N. are CNPq Research Productivity Fellows. Publisher Copyright: © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society Copyright: Copyright 2019 Elsevier B.V., All rights reserved.
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8422b166-0bbb-451a-a225-a928f7b887a9
date added to LUP
2021-09-21 19:53:16
date last changed
2024-06-01 15:57:16
@article{8422b166-0bbb-451a-a225-a928f7b887a9,
  abstract     = {{<p>New Findings: What is the central question of this study? What are the temporal responses of mitochondrial respiration and mitochondrial responsivity to insulin in soleus muscle fibres from mice during the development of obesity and insulin resistance? What is the main finding and its importance? Short- and long-term feeding with a high-fat diet markedly reduced soleus mitochondrial respiration and mitochondrial responsivity to insulin before any change in glycogen synthesis. Muscle glycogen synthesis and whole-body insulin resistance were present after 14 and 28 days, respectively. Our findings highlight the plasticity of mitochondria during the development of obesity and insulin resistance. Abstract: Recently, significant attention has been given to the role of muscle mitochondrial function in the development of insulin resistance associated with obesity. Our aim was to investigate temporal alterations in mitochondrial respiration, H<sub>2</sub>O<sub>2</sub> emission and mitochondrial responsivity to insulin in permeabilized skeletal muscle fibres during the development of obesity in mice. Male Swiss mice (5–6 weeks old) were fed with a high-fat diet (60% calories from fat) or standard diet for 7, 14 or 28 days to induce obesity and insulin resistance. Diet-induced obese (DIO) mice presented with reduced glucose tolerance and hyperinsulinaemia after 7 days of high-fat diet. After 14 days, the expected increase in muscle glycogen content after systemic injection of glucose and insulin was not observed in DIO mice. At 28 days, blood glucose decay after insulin injection was significantly impaired. Complex I (pyruvate + malate) and II (succinate)-linked respiration and oxidative phosphorylation (ADP) were decreased after 7 days of high-fat diet and remained low in DIO mice after 14 and 28 days of treatment. Moreover, mitochondria from DIO mice were incapable of increasing respiratory coupling and ADP responsivity after insulin stimulation in all observed periods. Markers of mitochondrial content were reduced only after 28 days of treatment. The mitochondrial H<sub>2</sub>O<sub>2</sub> emission profile varied during the time course of DIO, with a reduction of H<sub>2</sub>O<sub>2</sub> emission in the early stages of DIO and an increased emission after 28 days of treatment. Our data demonstrate that DIO promotes transitory alterations in mitochondrial physiology during the early and late stages of insulin resistance related to obesity.</p>}},
  author       = {{Brunetta, Henver Simionato and de Paula, Gabriela Cristina and de Oliveira, Jade and Martins, Eduarda Lopes and dos Santos, Gustavo Jorge and Galina, Antonio and Rafacho, Alex and de Bem, Andreza Fabro and Nunes, Everson Araújo}},
  issn         = {{0958-0670}},
  keywords     = {{diet-induced obesity; insulin resistance; mitochondrial function}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  pages        = {{306--321}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Experimental Physiology}},
  title        = {{Decrement in resting and insulin-stimulated soleus muscle mitochondrial respiration is an early event in diet-induced obesity in mice}},
  url          = {{http://dx.doi.org/10.1113/EP087317}},
  doi          = {{10.1113/EP087317}},
  volume       = {{104}},
  year         = {{2019}},
}