Muscle Oxidative Stress Plays a Role in Hyperthyroidism-Linked Insulin Resistance
Gianluca Fasciolo1, Gaetana Napolitano2,3, Marianna Aprile4
1Dipartimento di Biologia, Università di Napoli Federico II, 80126 Naples, Italy.
Abstract:
While a low level of ROS plays a role in cellular regulatory processes, a high level can lead to oxidative stress and cellular dysfunction. Insulin resistance (IR) is one of the dysfunctions in which oxidative stress occurs and, until now, the factors underlying the correlation between oxidative stress and IR were unclear and incomplete. This study aims to explore this correlation in skeletal muscle, a tissue relevant to insulin-mediated glucose disposal, using the hyperthyroid rat as a model of oxidative stress. The development of IR in the liver from hyperthyroid animals has been widely reported, whereas data concerning the muscle are quite controversial. Thus, we investigated whether hyperthyroidism induces IR in skeletal muscle and the role of oxidative stress in this process. Particularly, we compared the effects of hyperthyroidism on IR both in the absence and presence of vitamin E (Vit E), acting as an antioxidant. Putative correlations between ROS production, oxidative stress markers, antioxidant capacity and changes in intracellular signalling pathways related to insulin action (AKT) and cellular stress response (EIF2α; JNK; PGC1α; BIP; and NRF1) were investigated. Moreover, we assessed the effects of hyperthyroidism and Vit E on the expression levels of genes encoding for glucose transporters (Slc2a1; Slc2a4), factors involved in lipid homeostasis and insulin signalling (Pparg; Ppara, Cd36), as well as for one of the IR-related inflammatory factors, i.e., interleukin 1b (Il1b). Our results suggest that hyperthyroidism-linked oxidative stress plays a role in IR development in muscle and that an adequate antioxidant status, obtained by vitamin E supplementation, that mitigates oxidative stress, may prevent IR development.
Insights
Hyperthyroidism-induced oxidative stress contributes to insulin resistance in skeletal muscle. Vitamin E supplementation mitigates this oxidative stress, potentially preventing insulin resistance development.
Area of Science:
- Biochemistry
- Cellular Biology
- Endocrinology
Background:
- High levels of reactive oxygen species (ROS) cause oxidative stress and cellular dysfunction, including insulin resistance (IR).
- The link between oxidative stress and IR in skeletal muscle, crucial for glucose disposal, remains incompletely understood.
- Hyperthyroidism is a known inducer of oxidative stress, but its effect on skeletal muscle IR is controversial.
Purpose of the Study:
- To investigate if hyperthyroidism induces IR in skeletal muscle.
- To elucidate the role of oxidative stress in hyperthyroidism-induced skeletal muscle IR.
- To assess the protective effect of vitamin E (Vit E) against hyperthyroidism-induced skeletal muscle IR.
Main Methods:
- Utilized a hyperthyroid rat model to study oxidative stress and IR in skeletal muscle.
- Compared the effects of hyperthyroidism on IR with and without vitamin E supplementation.
- Analyzed ROS production, oxidative stress markers, antioxidant capacity, and intracellular signaling pathways (AKT, EIF2α, JNK, PGC1α, BIP, NRF1).
- Assessed gene expression of glucose transporters (Slc2a1, Slc2a4), lipid homeostasis factors (Pparg, Ppara, Cd36), and inflammatory factors (Il1b).
Main Results:
- Hyperthyroidism induced IR in skeletal muscle, correlating with increased ROS production and oxidative stress markers.
- Vitamin E supplementation reduced oxidative stress and ameliorated IR development in hyperthyroid rats.
- Changes in key signaling pathways and gene expression related to glucose transport, lipid metabolism, and inflammation were observed.
Conclusions:
- Hyperthyroidism-associated oxidative stress plays a significant role in the development of skeletal muscle IR.
- Maintaining adequate antioxidant status through vitamin E supplementation can mitigate oxidative stress and potentially prevent IR.
- These findings highlight the importance of antioxidant interventions in managing metabolic dysfunction associated with oxidative stress.
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