Journal article
Skeletal muscle type-specific mitochondrial adaptation to high-fat diet relies on differential autophagy modulation
The FASEB journal, Vol.35(10), pp.e21933-n/a
10/01/2021
DOI: 10.1096/fj.202001593RR
PMID: 34555201
Abstract
In obesity, skeletal muscle mitochondrial activity changes to cope with increased nutrient availability. Autophagy has been proposed as an essential mechanism involved in the regulation of mitochondrial metabolism. Still, the contribution of autophagy to mitochondrial adaptations in skeletal muscle during obesity is unknown. Here, we show that in response to high-fat diet (HFD) feeding, distinct skeletal muscles in mice exhibit differentially regulated autophagy that may modulate mitochondrial activity. We observed that after 4 and 40 weeks of high-fat diet feeding, OXPHOS subunits and mitochondrial DNA content increased in the oxidative soleus muscle. However, in gastrocnemius muscle, which has a mixed fiber-type composition, the mitochondrial mass increased only after 40 weeks of HFD feeding. Interestingly, fatty acid-supported mitochondrial respiration was enhanced in gastrocnemius, but not in soleus muscle after a 4-week HFD feeding. This increased metabolic profile in gastrocnemius was paralleled by preserving autophagy flux, while autophagy flux in soleus was reduced. To determine the role of autophagy in this differential response, we used an autophagy-deficient mouse model with partial deletion of Atg7 specifically in skeletal muscle (SkM-Atg7(+/-) mice). We observed that Atg7 reduction resulted in diminished autophagic flux in skeletal muscle, alongside blunting the HFD-induced increase in fatty acid-supported mitochondrial respiration observed in gastrocnemius. Remarkably, SkM-Atg7(+/-) mice did not present increased mitochondria accumulation. Altogether, our results show that HFD triggers specific mitochondrial adaptations in skeletal muscles with different fiber type compositions, and that Atg7-mediated autophagy modulates mitochondrial respiratory capacity but not its content in response to an obesogenic diet.
Details
- Title: Subtitle
- Skeletal muscle type-specific mitochondrial adaptation to high-fat diet relies on differential autophagy modulation
- Creators
- Pablo E. Morales - University of ChileMatias Monsalves-Alvarez - University of ChileSatya Murthy Tadinada - University of IowaMatthew P. Harris - University of IowaAndrea Ramirez-Sagredo - University of ChileJafet Ortiz-Quintero - University of ChileMayarling Francisca Troncoso - University of ChileNicole De Gregorio - University of ChileXimena Calle - University of ChileRenata O. Pereira - University of IowaVitor A. Lira - University of IowaAlejandra Espinosa - University of ChileE. Dale Abel - University of IowaSergio Lavandero - University of Chile
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.35(10), pp.e21933-n/a
- Publisher
- Wiley
- DOI
- 10.1096/fj.202001593RR
- PMID
- 34555201
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 19
- Grant note
- FONDECYT 1161156; FONDECYT 1200490; FONDAP 15130011; FONDECYT 1181774 / Agencia Nacional de Investigacion y Desarrollo (ANID), Chile DK092065; R01HL108379 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/01/2021
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Endocrinology and Metabolism; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984259648002771
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