Download - Leptin ppt
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LEPTIN(THE WONDER HORMONE)
A Concise Presentation
By
Mr. Deepak Sarangi M.Pharm.
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1. INTRODUCTION2. LEPTIN RECEPTOR3. ROLE OF LEPTIN IN DIFFERENT WAYS4. PHYSIOLOGICAL EFFECTS OF LEPTIN5. LEPTIN OR INSULIN MECHANISM IN WEIGHT LOSS OR GAIN6. INFLAMMATORY RESPONSE7. REGULATION OF LEPTIN EXPRESSION8. FEED BACK LOOP DETERMINING THE FOOD INTAKE9. OBESITY & LEPTIN RELATION10. LEPTIN RESISTANCE ( LIKE INSULIN RESISTANCE )11. RULES OF LEPTIN DIET12. DRUGS OF LEPTIN13. CONCLUSION14. REFERENCES
CONTENTS
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Leptin was discovered in 1994. Derived its name from leptos ( THIN ). Leptin is a hormone consist of 167 A.A. Leptin regulate body energy homeostasis, food intake, storage
and expenditure, fertility and immune functions.
INTRODUCTION
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Three theories evolved:1. Thermo regulation influenced the VMH.2. GLUCOSTATIC THEORY-Plasma glucose regulated over
all energy stores.3. LIPOSTATIC THEORY-Product of fat metabolism that
circulated in the blood and interacted with the VMH Factor was discovered in 1994 by Dr. JEFFREY
FRIEDMAN’S team. Factor was termed ‘LEPTIN’.
How Leptin Is Discovered
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It is16 KDa protein encoded by ob gene. Expressed & secreted by-adipocytes, placenta, gastric
epithelium. Leptin receptor is directly proportional to the total amount of
fat in the body. It has High degree of homology in sequence of amino acids.
LEPTIN (obesity gene coded)
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Folding pattern compatible with the helical cytokines
4 antiparallel helices each about 5-6 turn long.
Two long loops connecting helices A-B and C-D, shorter loop connecting helices B-C.
It Acts as binding protein. It has tail with 34 A.A residues-OB-Ra
form.
STRUCTURE OF LEPTIN
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ROLE OF LEPTIN IN THERMOGENESIS
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SIGNALLING PATHWAY OF LEPTIN ACTION
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Decrease hunger and food consumption – inhibition of neuropeptide Y synthesis.
Food intake linked to its ability to regulate the neuroendocrine system.
ROLE OF LEPTIN IN REGULATION OF FOOD INTAKE AND BOBY WEIGHT
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36 A.A residue produce in the arcuate nucleus of the hypothalamus. Rich in tyrosine residues.
It is a Appetite stimulating hypothalamic peptide. Found in many organ, high level of NPY are found in brain stem and
hypothalamus. Stimulates leptin production in adipose tissue by increasing food intake
and insulin secretion. It acts through the parasympathetic nervous system.
NEUROPEPTIDE Y
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Fertility influenced by stored body fat. Leptin signals the onset of puberty. Regulates hypothalamic- pituitary- ovarian function.
ROLE OF LEPTIN IN REPRODUCTION
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Inhibits intracellular lipid concentration. Activates 5-AMP- activated protein kinase ( AMPK ). Inhibits acetyl coenzyme-A carboxylase ( ACC ). Increase in fatty acid oxidation and reducing the fat tissue in
muscles and liver. Increase in insulin sensitivity.
ROLE OF LEPTIN IN LIPID METABOLISM
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1. Regulation of food intake, energy expenditure and body weight.
2. Thermogenesis.3. Reproductive function.4. Suppressed bone formation.5. Directly act on the cells of liver and muscles.6. Related to inflammatory response.7. Contribute to early haemotopoiesis.
PHYSIOLOGICAL EFFECTS OF LEPTIN
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LEPTIN / INSULIN MECHANISM IN WEIGHT LOSS OR GAIN
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Long form of leptin receptor is expressed by T-lymphocytes, bone marrow, spleen.
Leptin released in response to inflammatory cytokines attenuating its response and hence. Modulating inflammatory response.
Stimulates the expression of POMC-processed to α-MSH. Against the auto aggressive effects of the immune system.
INFLAMMATORY RESPONSE
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Two transcription factors PPAR and C/EBPα control the adipocyte differentiation.
C/EBPα promoted the leptin expression. PPAR decrease leptin expression.
Regulated by environmental and hormonal factors.
REGULATION OF LEPTIN EXPRESSION
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Inducers & Suppressers Effect Species
Feeding + Rodent + man
Glucocorticoids + Rodent + man
Insulin + Rodent
Cytokines + Rodent
Obesity + Rodent + man
Fasting - Rodent + man
Pertussis toxin - Rodent
Receptor antagonists - Rodent
Thiazolidinediones - Rodent
cAMP - Rodent
INDUCERS AND SUPPRESSERS OF LEPTIN EXPRESSION
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Food intake trigger the output of glucocorticoids and insulin. Favour fat accumulation & increase leptin. Leptin travels to hypothalamus. Regulates body mass & control body energy intake, energy
expenditure. NPY also regulate body fat mass.
FEED BACK LOOP DETERMINING THE FOOD INTAKE
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It is main focus of leptin research. Dramatic effects on obesity in mice. In human a body mass index over 27.3 for man & 27.8 for
women. Hypothalamic insensitivity to leptin-fundamental mechanism
of obesity.
OBESITY AND LEPTIN RELATION
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It is caused by mutation of the gene for leptin receptor in the brain.
Post receptor abnormalities in leptin signal transduction. Impaired leptin transport across blood brain barrier.
LEPTIN RESISTANCE ( LIKE INSULIN RESISTANCE )
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1) Human fat cells also manufacture leptin protein ( 167 A.A ).2) Mutation in gene for leptin or its receptor can also Leptin
resistance.3) High blood concentration leptin indicates leptin resistance.4) Extreme obesity in 5 members of 2 families that are
homozygous for mutation in their Leptin gene.
LEPTIN IN HUMANS
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7) Recombinant human leptin is available(Metreleptin).8) The 16 September 1999 issue the New England Journal of 9
Medicine reports-9 year old girl homozygous for frame shift mutation leptin gene.
9) Factor in obesity-3 adrenoreceptor.10) Defect contribute leptin resistance / leptin expression.11) A paradox exists-comparison between mouse & human
research cannot be made.
Contd…
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Weight lost with mutated OB gene. Not effective without genetic defect ob gene. More obese less sensitive to high level leptin.
LEPTIN RESEARCH RESULTS
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More focus on leptin receptor and involvement in leptin resistance.
Relation to reproduction. Mechanisms involved in regulation of leptin.
FUTURE PROSPECTS
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1. Never eat after dinner.2. Eat three meals a day.3. Do not eat large meals.4. Eat a break fast containing protein.5. Reduce the amount of carbohydrates eaten.
RULES OF LEPTIN DIET
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METRELEPTIN
Generic Name:metreleptin ( MET re LEP tin )
Brand Name: Myalept
DRUGS OF LEPTIN
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Metreleptin is used together with diet to treat complications caused by leptin deficiency in people who have lipodystrophy ( also called fat redistribution ). Lipodystrophy ( LIP-oh-DIS-tro-fee ) is a problem with the way the body stores fat.
But metreleptin is not used for people who have lipodystrophy caused by taking medicine to treat HIV or AIDS.
Metreleptin may also be used for purposes not listed in this medication guide.
METRELEPTIN (Drug)
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Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; rapid heart rate, feeling like you might pass out; swelling of your face, lips, tongue or throat.
In some people, metreleptin can trigger an immune response to the medicine, making it less effective or causing certain side effects. Call your doctor if u develop:
Any signs of a new infection ( fever, chills, night sweats, weight loss, swollen glands, flu symptoms ).
Changes in your blood sugar levels ( if you are diabetic ). or Worsening of your lipodystrophy symptoms.
SIDE EFFECTS OF METRELEPTIN
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Greater than 40kg: Males: -initial dose: 2.5mg/day subcutaneously. -Maximum dose:10mg/day.
Female: -Initial dose:5mg/day subcutaneously. -Maximum dose:10mg/day.
METRELEPTIN DOSING INFORMATION
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Much more research needs to be done to fully realize the potential of leptin in the body
When the medical community does learn more about leptin’s control & regulation, it will surely have a profound impact on the treatment of obesity , infertility
CONCLUSION
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1. Friedman JM, ( 1996 ). leptin & the control of body weight Proceeding of the nutrition society of Australia, vol-20,pg no: 1-2.
2. Friedman, J.M., HALAAS, J.L ( 1998 ) leptin and the regulation of body weight in body weight, British Journal of Nutrition vol-395, pg.no:763-770.
3. Anoja, S. Atele , leptin gut & food intake, Journal of clinical Pharmacol vol-63, ( 2002 ), pg.no:1579-1583.
4. Oral EA, Simha V, Ruiz E. Leptin-replacemant therapy for lipodystrophy, New Engld J Med. vol-346 ( 8 ) pg.no:570-578.
REFERENCES
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