Hormonal
Excessive mitochondrial ROS production in obesity drives insulin resistance by activating stress kinases like JNK and NF-κB, whereas controlled, low-level ROS signaling is required for normal insulin sensitivity and secretion.
In obesity, high levels of mitochondrial reactive oxygen species (ROS) contribute to insulin resistance by activating stress pathways like JNK. However, low levels of ROS are necessary for normal insulin function. Therefore, simply taking high-dose antioxidants to 'fight oxidative stress' may not be effective and could potentially interfere with necessary metabolic signaling. Focus on interventions that improve mitochondrial efficiency rather than just scavenging ROS.
The excess supply of energy substrates in obesity is believed to lead to increased mitochondrial dysfunction and ROS signaling, which may underlie insulin resistance... In the presence of high ROS levels, JNK is activated through various mechanisms, which may partly underlie insulin resistance in individuals with obesity... other data demonstrate the opposite, that ROS is required for insulin secretion by b-cells as well as insulin sensitivity
Why this rating
The paper is a review citing multiple animal models and human studies, establishing strong mechanistic plausibility, though it notes paradoxes and measurement challenges.
Source
Reactive Oxygen Species and Oxidative Stress in Obesity—Recent Findings and Empirical Approaches
Fiona McMurray et al. · Obesity · 2016
DOI 10.1002/oby.21654
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