Targeting mitochondrial alterations to prevent type 2 diabetes—Evidence from studies of dietary redox‐active compounds

Abstract

As a growing epidemic, type 2 diabetes mellitus (T2DM) has significantly affected the individual's quality of life and economy of the society. Understanding the mechanisms of the disease and discovery of new therapeutic options has become more urgent than ever before. Mitochondrial alterations (e.g. functional alterations, and impaired biogenesis and dynamics) are strongly associated with the development of T2DM. Accumulation of reactive oxygen species or intermediates of incomplete fatty acid oxidation due to mitochondrial deficiency activates stress kinases and dampens insulin signaling. Redox-active compounds such as resveratrol, pyrroloquinoline quinone, and hydroxytyrosol can potently counteract reactive oxygen species, and improve mitochondrial function and biogenesis. Therefore, targeting the mitochondrial alterations with these redox-active compounds may lead to new therapeutic or preventive options for T2DM. In this article, we review the molecular mechanisms of mitochondrial alterations in T2DM, and the action of redox-active compounds to reverse mitochondrial changes and oxidative stress in T2DM. In addition, the current challenges and future directions are discussed and prospected.

Modulation of hepatic lipid metabolism by olive oil and its phenols in nonalcoholic fatty liver disease

“…The efficacy of mitochondria‐targeted therapy on NAFLD is provided by the administration of compounds that improve bioenergetics and reduce oxidative stress . For example, dietary curcumin, a phenolic compound of Curcuma longa largely used in the Indian cuisine, was effective in experimental NAFLD, by increasing mitochondrial antioxidants, lowering mitochondrial ROS and improving mitochondrial function .…”

Targeting FoxO1 with AS1842856 Suppresses Adipogenesis

“…[1][2][3] Characterized by excess adiposity, obese individuals show aberrant glucose and lipid metabolism. 4 The resultant glucotoxicity and lipoxicity have been found to impair endocrine (e.g., insulin secretion and signaling pathway) and cardiovascular functions, linking obesity to higher risks of type 2 diabetes mellitus (T2DM) and heart diseases.…”

Hydroxytyrosol and Cytoprotection: A Projection for Clinical Interventions

“…The antioxidant properties of HT are related to hydrogen-atom donation and the ability to improve radical stability by forming an intramolecular hydrogen bond between the free hydrogens of their hydroxyl groups and their phenoxyl radicals [22]. The beneficial effects of HT have been demonstrated in human, cellular and animal models, mainly consumed as EVOO [17,23] The HT from EVOO has also shown to increase insulin sensitivity and the secretory capacity of β-pancreatic cells, thus reducing the risk of developing metabolic syndrome. The phenolic content of olive oil depends on the place of cultivation, climate, variety of the olive, and its level of ripening at the time of harvest, reaching levels of 100–600 mg/kg, and approximately 50% of that phenolic content corresponds to HT and its derivatives [24,25].…”

“…Moreover, HT provides other beneficial benefits that may be of importance for human health [8], namely anti-inflammatory [9] and anticancer [10] effects, enhancement of endothelial and vascular function [11], anti-steatotic [7,12] properties, and improvement of endoplasmic reticulum stress [13], autophagy [14] and mitochondrial function [15]. Interestingly, HT is the only polyphenol recognized by the European Food Safety Authority as a protector of low density lipoproteins (LDL) from oxidative damage [16], considering the finding that HT reduces the expression of adhesion molecules in endothelial cells, preventing the oxidation of LDL [17]. In order to obtain this effect, 5 mg of HT and its derivatives should be consumed in the form of extra virgin olive oil (EVOO) per day, which can be easily achieved in a healthy diet [16,18].…”