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62 Moreover, small molecule inhibitors of LDHA, such as GSK2837808A, FX-11, galloflavin, and N-hydroxyindole-based compounds, inhibit pyruvate-to-lactate conversion, and may possess the potential to regulate lactylation

VPA is a branched chain carboxylic acid (2-propylpentanoic acid or di-n-propylacetic acid), with a chemical structure very similar to that of short chain fatty acids (Fig

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]

Taken together, current evidence supports three balanced conclusions