This document discusses leptin, a hormone that regulates body weight. It describes how leptin is produced in fat cells and acts in the hypothalamus to reduce appetite. Leptin resistance, where the body becomes insensitive to leptin, is a major factor in obesity. The document also outlines the physiological effects of leptin, factors that influence its expression, and potential leptin-targeting drugs for treating obesity and related conditions.

1. A Concise Presentation
By
Mr. Deepak Sarangi M.Pharm.

2. 1. INTRODUCTION
2. LEPTIN RECEPTOR
3. ROLE OF LEPTIN IN DIFFERENT WAYS
4. PHYSIOLOGICAL EFFECTS OF LEPTIN
5. LEPTIN OR INSULIN MECHANISM IN WEIGHT LOSS OR GAIN
6. INFLAMMATORY RESPONSE
7. REGULATION OF LEPTIN EXPRESSION
8. FEED BACK LOOP DETERMINING THE FOOD INTAKE
9. OBESITY & LEPTIN RELATION
10. LEPTIN RESISTANCE ( LIKE INSULIN RESISTANCE )
11. RULES OF LEPTIN DIET
12. DRUGS OF LEPTIN
13. CONCLUSION
14. REFERENCES

3.  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.

4. 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’.

5.  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.

6.  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.

10.  Decrease hunger and food consumption – inhibition of
neuropeptide Y synthesis.
 Food intake linked to its ability to regulate the neuroendocrine
system.

11.  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.

12.  Fertility influenced by stored body fat.
 Leptin signals the onset of puberty.
 Regulates hypothalamic- pituitary- ovarian function.

13.  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.

14. 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.

16.  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.

17.  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.

18. 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

19.  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.

20.  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.

22.  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.

23. 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.

24. 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.

25.  Weight lost with mutated OB gene.
 Not effective without genetic defect ob gene.
 More obese less sensitive to high level leptin.

26.  More focus on leptin receptor and involvement in leptin
resistance.
 Relation to reproduction.
 Mechanisms involved in regulation of leptin.

27. 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.

28. METRELEPTIN
Generic Name:metreleptin ( MET re LEP tin )
Brand Name: Myalept

29.  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.

30.  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.

31. Greater than 40kg:
Males:
-initial dose: 2.5mg/day subcutaneously.
-Maximum dose:10mg/day.
Female:
-Initial dose:5mg/day subcutaneously.
-Maximum dose:10mg/day.

32. 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

33. 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.