Arachidonic Acid Protects Skeletal Muscle Against Hyperglycaemia-Induced Muscle Atrophy by Modulating Myogenesis and Regulating KLF15 Expression in C57Bl/6 Mice
Akash Mitra, Debajit Chaudhury, Akhila Balakrishna Rai, Undurti N. Das, Thottethodi Subrahmanya Keshava Prasad, Bipasha Bose, Sudheer Shenoy P
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Abstract
Glucotoxicity or hyperglycemia as a consequence of Type 1 diabetes affects numerous tissues, including skeletal muscles, and translates to muscle wasting or atrophy. Since 40% of the total body weight comprises skeletal muscles, and because this tissue plays an essential role in voluntary movement, protecting its integrity is crucial for maintaining whole-body homeostasis. Although different studies have investigated the role of arachidonic acid (AA) in salvaging skeletal muscle atrophy, the underlying mechanisms concerning the activation of muscle stem cells and the regenerative process need further elucidation. In this study, we use a streptozotocin-induced Type 1 diabetes mouse model to study the effects of AA in mitigating the reduction in the myogenesis process and also try to elaborate on the anti-atrophic and anti-inflammatory properties of AA, which help to rescue the levels of sarcomeric protein. To carry out this study, male C57BL/6 mice (5-week-old) were divided into Control, diabetic (STZ) and AA-administered diabetic (STZ + AA) groups (n = 6 mice per group). The study involved a short-term treatment regime of 5 days. Muscle stem cell activation, inflammation, and muscle fiber integrity were assessed using molecular techniques. A global proteomic study provided insights into differential protein expression status. Histological analysis revealed the rescue of muscle cells at different stages of myogenesis and fiber integrity upon AA administration in diabetic mice. Moreover, the proteomic results supported the upregulation of stemness upon AA treatment as well. Additionally, it also showed the rescue of the sarcomeric protein repertoire. The findings suggest that AA holds myogenic properties, which stem from its role in activating the muscle stem cells, and this can be used as a potential therapeutic supplement for diabetic patients.
期刊介绍：
The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
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