How does tesofensine burn fat?

    Tesofensine burns fat through a dual-action mechanism that combines appetite suppression with a slight increase in fat oxidation and energy expenditure.

    Its primary action is in the brain, where it works as a triple monoamine reuptake inhibitor. This means it blocks the reabsorption of three key neurotransmitters:

    ●Noradrenaline

    ●Dopamine

    ●Serotonin

    By increasing the levels of these neurotransmitters, tesofensine produces its weight-loss effects through several pathways:

    1. Appetite Suppression (Primary Mechanism)

    The increase in neurotransmitters, particularly serotonin and dopamine, signals the brain to reduce hunger and increase feelings of fullness (satiety). This is considered the primary mechanism by which tesofensine leads to weight loss. Research shows it also modulates the brain's pleasure response to food, which can reduce the desire to eat.

    A 2024 study provided new insight into this process, finding that tesofensine inhibits a specific subset of GABAergic neurons in the Lateral Hypothalamus (LH)-a brain region that promotes feeding behavior. Silencing these neurons further enhanced tesofensine's appetite-suppressing effects.

    2. Increased Fat Oxidation

    Beyond just reducing caloric intake, tesofensine has a direct effect on how the body uses energy. A clinical study showed that tesofensine increased 24-hour fat oxidation by 15% (an additional 18 grams of fat burned per day) compared to a placebo.

    3. Slight Increase in Energy Expenditure

    While the effect is modest, research indicates tesofensine can slightly boost metabolism. The same study found a 4.6% increase in energy expenditure during nighttime (resting) hours. Another source noted a 6% increase in resting energy expenditure.

    Summary of Effects

    The table below summarizes the key findings from a clinical study on tesofensine:

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