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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Mitochondrial substrate availability and its role in lipid-induced insulin resistance and proinflammatory signaling in skeletal muscle.
Diabetes 62, 3426-3436 (2013)
The relationship between glucose and lipid metabolism has been of significant interest in understanding the pathogenesis of obesity-induced insulin resistance. To gain insight into this metabolic paradigm, we explored the potential interplay between cellular glucose flux and lipid-induced metabolic dysfunction within skeletal muscle. Here, we show that palmitate (PA)-induced insulin resistance and proinflammation in muscle cells, which is associated with reduced mitochondrial integrity and oxidative capacity, can be attenuated under conditions of glucose withdrawal or glycolytic inhibition using 2-deoxyglucose (2DG). Importantly, these glucopenic-driven improvements coincide with the preservation of mitochondrial function and are dependent on PA oxidation, which becomes markedly enhanced in the absence of glucose. Intriguingly, despite its ability to upregulate mitochondrial PA oxidation, glucose withdrawal did not attenuate PA-induced increases in total intramyocellular diacylglycerol and ceramide. Furthermore, consistent with our findings in cultured muscle cells, we also report enhanced insulin sensitivity and reduced proinflammatory tone in soleus muscle from obese Zucker rats fed a 2DG-supplemented diet. Notably, this improved metabolic status after 2DG dietary intervention is associated with markedly reduced plasma free fatty acids. Collectively, our data highlight the key role that mitochondrial substrate availability plays in lipid-induced metabolic dysregulation both in vitro and in vivo.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Fatty-acid Oxidation ; Factor-kappa-b ; Receptor Substrate-1 ; Calorie Restriction ; Ceramide Synthesis ; Cells ; Dysfunction ; Activation ; Expression ; Palmitate
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
Zeitschrift
Diabetes
Quellenangaben
Band: 62,
Heft: 10,
Seiten: 3426-3436
Verlag
American Diabetes Association
Verlagsort
Alexandria, VA.
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed