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Also, hyperactivation of the hypothalamus-pituitary-adrenal axis, altered metabolic clearance of cortisol, coupled with changes in corticosteroid-binding globulin and corticosteroid receptor sensitivity may contribute to increasing cortisol availability [79, 84,85,86,87,88,89] Together, these processes create a state of tissue-specific cortisol excess, promoting visceral adiposity, insulin resistance, and metabolic dysfunction [79, 84,85,86,87,88,89] It is however noteworthy that the relationship between cortisol levels and obesity are inconsistent, as some investigators have documented positive, null, or even inverse associations, likely reflecting complexities in glucocorticoid production, variable cortisol clearance, and metabolic regulation [84, 90,91,92,93,94,95]

35 were preclinical (animal studies)

British Journal of Nutrition, 108 (S1), S66S73

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This highlights how dysregulated JNK activity can impair oxidative stress defense mechanisms, potentially contributing to pathologic conditions like vitiligo 70