Makindo Medical Notes

🧬 Leptin is a hormone (adipokine) secreted mainly by adipocytes. It plays a central role in regulating satiety, energy expenditure, and neuroendocrine function. In obesity, high circulating leptin levels often fail to suppress appetite → a phenomenon known as leptin resistance.

📌 About

• Leptin acts as the body’s “energy thermostat” by signalling to the brain about fat storage levels.
• Plasma leptin levels rise with increasing adiposity and fall during weight loss.
• Leptin receptors are concentrated in the hypothalamus and brainstem, where they influence hunger, energy expenditure, and hormonal balance.
• Most obese individuals show elevated leptin without appetite suppression → “leptin resistance.”
• This resistance is thought to be a key driver of obesity pathophysiology.

🧠 Mechanisms of Action

• Acts on hypothalamic nuclei (ventromedial, dorsomedial, and arcuate nucleus) to reduce appetite and increase energy use.
• Stimulates the sympathetic nervous system (SNS), particularly renal sympathetic nerves.
• Leptin is both a vasodilator (via nitric oxide) and a pressor agent (via SNS activation) → complex cardiovascular effects.

⚡ Cardiovascular Effects

• High leptin levels correlate strongly with blood pressure elevation in obesity.
• Leptin-driven sympathetic activation increases renal sodium retention and vascular tone.
• Hyperleptinaemia is considered an independent cardiovascular risk factor.
• Paradoxically, leptin also promotes vasodilation through NO release → creating a balance of opposing forces.

📊 Clinical & Research Relevance

• Obesity: High leptin but reduced response → appetite persists despite energy surplus.
• Cardiovascular disease: Hyperleptinaemia linked with hypertension, LV hypertrophy, and metabolic syndrome.
• Genetic leptin deficiency: Rare cause of severe early-onset obesity; responds dramatically to leptin replacement therapy.
• Therapeutics: Trials with leptin replacement or leptin-sensitising drugs have had limited success in common obesity due to resistance.

📚 References

• Friedman JM, Halaas JL. “Leptin and the regulation of body weight.” Nature, 1998.
• Mark AL. “Selective leptin resistance: a new concept in leptin physiology.” Hypertension, 2008.
• Leptin – StatPearls (NCBI)