Role of Leptin in Obesity

Speaker: Resource Faculty:

Rajat Chaudhary Dr. Dilip Thakur
Additional Professor
Dept. of Basic & clinical physiology
Main Objective
-Hypothalamic regulation of food intake and its
disorders with reference to obesity
 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.
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
What does Leptin do?

Increases metabolic rate/energy expenditure

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

Stimulation Destruction

Increased eating response Causes severe fatal anorexia

Ventromedial nucleus
Satiety center
Satiety(sense of fullness)

Stimulation Destruction

Causes feeling of satiety and Causes hyperphagia and may

cessation of eating lead to Hypothalamic obesity
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
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.
Defects in leptin leading to obesity
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
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.
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