Obesity has been found be linked mainly with genetics.

1. Speaker:
Rajat Chaudhary
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?
It works through two distinct types of
neurons in arcuate nucleus of Hypothalamus:
POMC/CART (Pro-opiomelanocortin/Cocaine
and Amphetamine regulated
transcripts)neurons
NPY/AgRP (Neuropeptide Y/Agouti-related
peptide)neurons

7.  Leptin stimulates POMC/CART neurons to produce
anorexigenic neuropeptide: Melanocyte Stimulating
Hormone that results in:
1. Endocrine changes
2. 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.

10. Neurotransmitters and Hormones that influence
feeding and satiety centers
Anorexins
• Leptin
• α- MSH
• CART (Cocaine and Amphetamine-
regulated Transcript)
• Insulin
• Cholecystokinin
• Peptide YY
• CRH
• CGRP(Calcitonin gene-related
peptide)
• Glucagon
• Oxytocin
• Somatostatin
Orexins
• Ghrelin
• AGRP (Agouti Related
Proteins)
• Neuropeptide Y
• Orexin A
• Orexin B
• β-Endorphins
• Galanin
• MCH (Melanin-Concentrating
Hormone)

12. Centers for regulating food intake

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

14. 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

15. 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

16. 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.

17. Defects in leptin leading to obesity

18. 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:
1. Changes to leptin receptor signaling particularly in arcuate
nucleus
2. Alterations during its formation
3. Saturation of leptin transporters

19. 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.

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