role of leptin in obesity
TRANSCRIPT
Role of Leptin in Obesity
Speaker:Rajat Chaudhary
Resource Faculty:Dr. Dilip ThakurAdditional ProfessorDept. 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 expenditureDecreases 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 changes2. 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• 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)
Centers for regulating food intake
Lateral NucleusFeeding Centre
Stimulation
Increased eating response
Destruction
Causes severe fatal anorexia
Ventromedial nucleusSatiety centerSatiety(sense of fullness)
Stimulation
Causes feeling of satiety and cessation of
eating
Destruction
Causes hyperphagia and may 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 obesityAlthough 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 nucleus2. Alterations during its formation3. 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.
ReferencesGuyton and Hall Textbook of Medical
PhysiologyGanong’s Review of Medical Physiologyhttp://
www.nature.com/nature/journal/v395/n6704/fig_tab/395763a0_F4.html