Our study highlights the pivotal role of amino acid residues L261, W264, F265, L268, and V269 in helix 8 of human APOE in adipose tissue metabolic activity, providing new insights into potential therapeutic strategies for morbid obesity using APOE4mut1, where these five hydrophobic amino acid residues have been replaced by Alanine. The gene discussed is APOE; the disease is morbid obesity.