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Under basal homeostatic conditions, Nrf2 is sequestered in the cytoplasm through its interaction with the adaptor protein KEAP1 (Kelch-like ECH-associated protein 1), which targets Nrf2 for ubiquitination and subsequent proteasomal degradation

The four-pathway model therefore targets appetite (GLP-1 and amylin through separate neuronal circuits), fat metabolism (GIP and glucagon), energy expenditure (glucagon primarily), and glucose homeostasis (GLP-1, GIP, and amylin all contribute through different mechanisms)

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