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Evidence indicates that chronic hyperglycemia and elevated free fatty acids (FFAs) levels trigger persistent ER stress, specifically by activating the PERK-eIF2-ATF4 pathway (Lemmer et al., 2021)

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These changes occur due to both reduced calorie intake and early metabolic effects

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That qualitative convergence, achieved through a different binding mode and signaling bias, is the central scientific point of the whole comparison