Animal model metabolomics studies reveal that HFD-induced NAFLD is characterized by hepatic saturated fatty acid (myristic acid, palmitic acid) and monounsaturated fatty acid (oleic acid) accumulation, accompanied by decreased gluconeogenic amino acid (glycine, alanine, aspartic acid, glutamic acid, proline) levels (95)
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Third, most inhibitors of NLRP3, NF-B, autophagy, ferroptosis, or senescence remain preclinical and lack regulatory approval, and there is a paucity of validated pharmacodynamic biomarkers in humans (e.g., CSF IL-1/IL-18, GSDMD-N, ex vivo NLRP3 assays) to confirm target engagement
Furthermore, AMPK agonists promote FAO and natural Treg differentiation via 1-adrenergic receptor signaling
