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Given that these positions are primarily located in the hydrophobic environment of the lipid bilayer, the mutation range for these amino acids was restricted to 11 non-polar amino acids: ACFGILMPVWY

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Metabolic rate increase and thermogenesis How tesofensine boosts metabolism: Norepinephrine stimulates beta-adrenergic receptors Activates thermogenesis in brown and white fat Increases basal metabolic rate 5-10% Enhanced fat oxidation (preferential fat burning) Similar to ephedrine effects but stronger Energy expenditure studies: Clinical trials showed increased resting energy expenditure 24-hour metabolic rate elevated 5-10% Translates to ~100-200 extra calories burned daily Combined with appetite suppression = larger deficit Thermogenesis mechanism: Why metabolism boost matters: Creates deficit even without appetite changes Counteracts metabolic adaptation Preserves lean mass better Enhanced fat loss vs muscle loss Different advantage vs GLP-1 agonists Cardiovascular cost: Increased metabolism = increased heart rate Blood pressure elevation Cardiac workload increased Major safety concern Why FDA rejected despite efficacy See best peptides for energy and fat loss peptides

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One is the classic issue of "causation versus correlation": Is food consumption going down because of the GLP-1 medication (a reasonable hypothesis given what the medication does), or is the decrease in food purchases a conscious switch to healthier eating that went hand in hand with a decision to start taking medication to control diabetes or lose weight