Role of Leptin in Obesity

Obesity has been found be linked mainly with genetics.

1. Role of Leptin in Obesity Speaker: Rajat C haudhary Resource Faculty: Dr. Dilip Thakur Additional Professor Dept. of Basic & clinical physiology

2. Main Objective -Hypothalamic regulation of food intake and its disorders with reference to obesity

3. Discovery of leptin 1950 Dr. Jeffrey Friedman’s team on 1994 - from the Greek word “ leptos ”, meaning thin. -Leptin is a 16-kilodalton adipocyte derived hormone that circulates in the serum in the free and bound form.

4. Sources of leptin - white adipose tissue It can also be produced by: Brown adipose tissue Placenta Ovaries Skeletal muscle Stomach Mammary epithelial cells Bone marrow Pituitary gland and Liver

5. What does Leptin do? Increases metabolic rate/energy expenditure Decreases food intake

6. How does it work?

7. Leptin stimulates POMC/CART neurons to produce anorexigenic neuropeptide: Melanocyte Stimulating Hormone that results in: Endocrine changes Increase sympathetic nerve activity This stimulates energy expenditure. Leptin inhibits NPY/ AgRP neurons that produce feeding-inducing ( orexigenic ) neuropeptide: Neuropeptide Y that results in inhibition of food intake.

8. Neurotransmitters and Hormones that influence feeding and satiety centers

9. Centers for regulating food intake

10. Lateral Nucleus Feeding Centre Stimulation Increased eating response Destruction Causes severe fatal anorexia

11. Ventromedial nucleus Satiety center Satiety(sense of fullness) Stimulation Causes feeling of satiety and cessation of eating Destruction Causes hyperphagia and may lead to Hypothalamic obesity

12. Other hypothalamic centres that regulate food intake Paraventricular nucleus(Satiety)- its lesion causes excessive eating behaviour Dorsomedial nucleus(GI Stimulation)- its lesion causes depressed eating behaviour Mammillary Body- partially control feeding reflexes such as licking the lips and swallowing

13. Feedback mechanism for control of food intake Feeding stage :-Peptide YY (PYY ), cholecystokinin (CCK ), and insulin are gastrointestinal hormones that are released - suppress further feeding. Excessive feeding: – Excess Fat –Increased leptin Production –Inhibition of food intake. Fasting stage :-Ghrelin is released by the stomach, stimulates appetite.

14. Defects in leptin leading to obesity

15. Leptin resistance and obesity Although leptin is a circulating signal that reduces appetite, in general, obese people have an unusually high circulating concentration of leptin. These people are said to be resistant to the effects of leptin. The high sustained concentrations of leptin from the enlarged adipose stores result in leptin desensitization. Causes of resistance: Changes to leptin receptor signaling particularly in arcuate nucleus Alterations during its formation Saturation of leptin transporters

16. Summary Leptin is peptide hormone secreted by adipose tissue that causes increase in metabolic rate and inhibition of food intake through hypothalamic signaling. Any lesion in hypothalamic centres may causes excessive eating behaviour resulting in obesity or fatal anorexia . Obese people have high amount of leptin but are resistant to its action due to leptin desensitization.

17. References Guyton and Hall Textbook of Medical Physiology Ganong’s Review of Medical Physiology http:// www.nature.com/nature/journal/v395/n6704/fig_tab/395763a0_F4.html