PRKAA1 and obesity due to melanocortin 4 receptor deficiency: Interestingly, recent research indicates that AMPK not only indirectly affects OA through metabolic disorders, which contribute to obesity and subsequent biomechanical stress on joints, but also directly participates in OA-related pathways to protect cells and tissues of the joint from stress-induced damage while mitigating inflammation (Liu-Bryan, 2015).