💉 Semaglutide Appetite Suppression Mechanism Simulator

The Arcuate Nucleus at Rest — Two Neuron Populations in Balance

Placeholder: baseline hunger and fullness signals held in dynamic equilibrium.

• ~30%: POMC/CART activity (placeholder baseline)
• ~68%: AgRP/NPY activity (placeholder baseline)
• ~2%: GLP-1R occupancy (placeholder, pre-dose)
• Elevated: Net appetite drive (placeholder fasting state)

POMC/CART neurons

Placeholder: anorexigenic neurons, low tonic activity at baseline.

AgRP/NPY neurons

Placeholder: orexigenic neurons dominate signaling before treatment.

Circuit balance

Placeholder: reciprocal inhibition sets the fasting appetite set point.

Semaglutide Crosses Into the Hypothalamus and Binds GLP-1 Receptors

Placeholder: circulating drug reaches arcuate nucleus receptors.

• ~38%: Receptor occupancy (placeholder mid-binding)
• yes: Circumventricular access (placeholder BBB-permeable zone)
• GLP-1R: Receptor type (placeholder class-B GPCR)
• minutes–hours: Binding onset (placeholder timescale)

Crossing the barrier

Placeholder: median eminence permeability allows central access.

Receptor docking

Placeholder: agonist occupies GLP-1 receptors on both neuron types.

Dose dependence

Placeholder: higher dose raises steady-state receptor occupancy.

POMC/CART Activated, AgRP/NPY Inhibited — the Circuit Flips

Placeholder: receptor activation drives opposite effects on each population.

• ~66%: POMC/CART activity (placeholder mid-shift)
• ~38%: AgRP/NPY activity (placeholder mid-shift)
• reciprocal: Signal direction (placeholder opposing shift)
• Neutral: Net appetite drive (placeholder transition point)

POMC excitation

Placeholder: alpha-MSH output rises as POMC neurons fire more.

AgRP inhibition

Placeholder: orexigenic firing rate drops under GLP-1R activation.

Cross-inhibition loosens

Placeholder: AgRP normally suppresses POMC; that brake eases.

Satiety Strengthens While Hunger Drive Weakens

Placeholder: combined neuron shift produces a stronger net fullness signal.

• ~80%: POMC/CART activity (placeholder strengthened)
• ~24%: AgRP/NPY activity (placeholder weakened)
• MC4R: Downstream target (placeholder melanocortin pathway)
• Suppressed: Net appetite drive (placeholder state)

Melanocortin output

Placeholder: alpha-MSH activates MC4R on second-order neurons.

Hunger drive decline

Placeholder: orexigenic tone falls well below baseline levels.

Signal integration

Placeholder: hypothalamus reads net balance as energy sufficiency.

Reduced Caloric Intake and a Weight-Loss Trajectory Over Weeks

Placeholder: sustained central suppression compounds into weight loss.

• 0–20: Weeks modeled (placeholder therapy window)
• declining: Caloric intake trend (placeholder trajectory)
• declining: Weight trajectory (placeholder cumulative)
• Suppressed: Net appetite drive (placeholder sustained state)

Weeks compound

Placeholder: cumulative weeks deepen the appetite-drive suppression.

Intake reduction

Placeholder: fewer daily calories consumed without deliberate restriction.

Weight trajectory

Placeholder: steady downward trend over the modeled 20 weeks.

Placeholder key insight: central hypothalamic shift, not gut alone, drives sustained suppression.