Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning agains
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Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes Kanwal Rehman 1
&
Kamran Haider 1 & Komal Jabeen 1,2 & Muhammad Sajid Hamid Akash 3
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) is a leading cause of deaths due to metabolic disorders in recent years. Molecular mechanisms involved in the initiation and development of IR and T2DM are multiples. The major factors include mitochondrial dysfunction which may cause incomplete fatty acid oxidation (FAO). Oleic acid upregulates the expression of genes causing FAO by deacetylation of PGC1α by PKA-dependent activation of SIRT1-PGC1α complex. Another potent factor for the development of IR and T2DM is endothelial dysfunction as damaged endothelium causes increased release of inflammatory mediators such as TNF-α, IL-6, IL-1β, sVCAM, sICAM, E-selectin and other proinflammatory cytokines. While, on the other hand, oleic acid has the ability to regulate E-selectin, and sICAM expression. Rest of the risk factors may include inflammation, β-cell dysfunction, oxidative stress, hormonal imbalance, apoptosis, and enzyme dysregulation. Here, we have highlighted how oleic acid regulates underlying causatives factors and hence, keeps surpassing effect in prevention and treatment of IR and T2DM. However, the percentage contribution of these factors in combating IR and ultimately averting T2DM is still debatable. Thus, because of its exceptional protective effect, it can be considered as an improved therapeutic agent in prophylaxis and/or treatment of IR and T2DM. Keywords Oleic acid . Insulin resistance . Inflammatory responses . Mitochondrial dysfunction
1 Introduction Type 2 diabetes mellitus (T2DM) is one of the global health problems, constituting the prevalence of 8.8% worldwide. Undoubtedly, the incidence of DM is increasing promptly, predominantly due to remarkable changes in the modern human lifestyle. Recently, DM is one of the most accelerated metabolic disorder, leading towards disruption in metabolic
Kanwal Rehman and Kamran Haider contributed equally to this work. * Kanwal Rehman [email protected] * Muhammad Sajid Hamid Akash [email protected] 1
Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan
2
Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan
3
Department of Pharmaceutical Chemistry, Government College University, Faisalabad, Pakistan
pathways, ultimately giving rise to the synthesis of hazardous metabolites and finally ending up in total organ failure [1, 2]. Regardless of recent advances in pharmaceutical along with technologic treatment options, DM still remains a major health epidemic. However, it was initially identified as an incurable chronic disease but now, healthy outcomes are expected in the amendment of DM symptoms and eventually its progression [3]. Insulin resistance (IR), which is
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