1. Effects of Leptin on Exercise and Health in Human

2. Human Leptin A protein of 167 amino acids. A molecular weight of 16 kDa, peptide hormone secreted by adipose tissue. the level in circulation is directly proportional to the total amount of fat in the body. regulates body weight and energy homeostasis via its actions on specific hypothalamic nuclei

4. Biosynthesis the major source of leptin: –brown adipose tissue, –placenta (syncytiotrophoblasts), –ovaries, skeletal muscle, –stomach (lower part of fundic glands), –mammary epithelial cells, –bone marrow, –Pituitary –and liver Leptin has also been discovered to be synthesised from gastric chief cells and P/D1 cells in the stomach

5. Leptin Production and Adipocyte

6. Biosynthesis Leptin is the product of the obese (ob) gene that is synthesized predominantly, although not exclusively, by white adipose tissue The Ob(Lep) gene (Ob for obese, Lep for leptin) is located on chromosome 7 (q31.31- q32.1) in humans.

7. Function Leptin acts on receptors in the hypothalamus of the brain where it inhibits appetite by –(1) counteracting the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus); – (2) counteracting the effects of anandamide (another potent feeding stimulant that binds to the same receptors as THC, the primary active ingredient of marijuana); –(3) promoting the synthesis of α-MSH, an appetite suppressant

8. Satiety Leptin binds to neuropeptide Y (NPY) neurons in the arcuate nucleus, in such a way that decreases the activity of these neurons. Leptin signals to the brain that the body has had enough to eat, producing a feeling of satiety

10. Regulation of satiety signals Model for regulation of the hindbrain response to satiety signals by hormonal input from the ARC. Adiposity signals such as insulin and leptin circulate in proportion to body fat mass and act on hypothalamic ARC neurons that project to hypothalamic areas such as the PVN these “second order” neurons project to hindbrain autonomic centers such as the NTS that process afferent input from satiety signals such as CCK.

12. Input from descending, leptin-sensitive hypothalamic projections is integrated in the NTS with vagally mediated input from CCK, such that the timing of meal termination is regulated by changes in body fat content

14. Interaction with amylin Co-administration of two neurohormones known to have a role in body weight control, amylin (produced by beta cells in the pancreas) and leptin (produced by fat cells), results in sustained, fat-specific weight loss in a leptin- resistant animal model of obesity

16. Leptin and Obesity obese individuals generally exhibit an unusually high circulating concentration of leptin the high sustained concentrations of leptin from the enlarged adipose stores result in leptin desensitization The pathway of leptin control in obese people doesn't adequately receive the satiety feeling subsequent to eating The pathway of leptin control in obese people doesn't adequately receive the satiety feeling subsequent to eating

18. As it circulates through the cerebrovasculature, transporters for leptin carry it across the BBB to enter the interstitial fluid of the brain Leptin functions are thought to occur through the leptin receptors mainly in the hypothalamic nuclei

19. Model of leptin regulation of NPY/GABA and POMC neurons in the ARC

20. Function Leptin acts on receptors in the hypothalamus of the brain where it inhibits appetite by –(1) counteracting the effects of neuropeptide Y(a potent feeding stimulant secreted by cells in the gut and in the hypothalamus); –(2) counteracting the effects of anandamide (another potent feeding stimulant that binds to the same receptors as THC, the primary active ingredient of marijuana); –(3) promoting the synthesis of α-MSH, an appetite suppressant

22. This inhibition is long-term, in contrast to the rapid inhibition of eating by cholecystokinin (CCK) and the slower suppression of hunger between meals mediated by PYY3-36. Peptide YY3-36 (PYY3-36), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal

24. Presynaptic Inhibition

25. The absence of leptin (or its receptor) leads to uncontrolled food intake and resulting obesity. Several studies have shown that fasting or following a very-low-calorie diet (VLCD) lowers leptin levels Dynamics of leptin due to an acute change in energy balance are related to appetite and eventually to food intake

27. Two neurohormones known to have a role in body weight control, amylin (produced by beta cells in the pancreas) and leptin (produced by fat cells),

28. Resting leptin responses to acute and chronic resistance training in type 2 diabetic men and women. Kanaley JA, Fenicchia LM, Miller CS, Ploutz-Synder LL, Weinstock RS, Carhart R, Azevedo JL Jr.Int J Obes Relat Metab Disord. 2001 Oct;25(10):1474-80. 17 controls and 13 type 2, obese diabetics, age 40-55 y resting blood samples drawn at 08:00 h (12 h postprandial) at the beginning of the study (pre-training) 24 h after a three repetition maximal weight lifting bout (acute) and 72 h after their last training bout of 6 weeks of resistance training (chronic) 24 h after a three repetition maximal weight lifting bout (acute) and 72 h after their last training bout of 6 weeks of resistance training (chronic)

29. Serum leptin concentrations were significantly higher in the type 2 diabetics than in the control group at pre-training Compared to pre-training, the leptin levels decreased after acute exercise in the diabetics but not in the control subjects The decreased resting leptin concentrations approximately 24 h post-acute exercise may be due to reduced glucose availability to the adipose tissue

31. Ten men completed an acute heavy-resistance exercise protocol (AHREP;50 total sets comprised of the squat, bench press, leg press, and lat pull-down) from 1500 to 1700 h. Blood was sampled hourly postexercise until 0600 h the next morning and also during a time-matched control period. Leptin concentrations were measured by an immunoradiometric assay. Resting energy expenditure (REE) was measured via indirect calorimetry using a ventilated hood beginning approximately 0600 h after both overnight conditions. Leptin concentrations experience a delayed reduction after resistance exercise in men. Nindl BC, Kraemer WJ, Arciero PJ, Samatallee N, Leone CD, Mayo MF, Hafeman D

32. The estimated caloric expenditure from the AHREP was 856 +/- 114 kcal. No differences between the control and exercise conditions were observed for serum leptin concentrations until 9 h postexercise. Significant interaction effects indicated lower serum leptin concentrations postexercise at hours 9, 10, 12, and 13. Significant interaction effects indicated lower serum leptin concentrations postexercise at hours 9, 10, 12, and 13. This delayed reduction was accompanied by a 12% elevation in morning-after REE

34. Leptin concentrations experience a delayed ( approximately 9 h) reduction in the systemic circulation after acute resistance exercise. This decline is likely associated with the disruption in metabolic homeostasis created by the high- intensity, long-duration, energy expenditure

36. Summary Leptin circulates at levels proportional to body fat. It enters the central nervous system (CNS) in proportion to its plasma concentration. Its receptors are found in brain neurons involved in regulating energy intake and expenditure. It controls food intake and energy expenditure by acting on receptors in the mediobasal hypothalamus

37. Response of leptin to muscular exercise. Physical exercise and or training can reduce fat mass Changes in energy expenditure and affect hormonal concentrations (insulin, cortisol, growth hormone, catecholamines, testosterone etc.) and metabolites (free fatty acids, lactic acid, triglycerides etc.).

38. Discussion What is your thinking about the relation between the human leptin and athletic performance? Could you draw a diagram to denote the leptid’s effect on POMC/CART and NPY/AgRP and Arcuate nucleus to change an eating behavior.

41. gut peptide cholecystokinin (CCK) hypothalamic arcuate nucleus (ARC) a key forebrain site of leptin action agouti-related peptide (AgRP), α-melanocyte-stimulating hormone (α-MSH). Pro-opiomelanocortin (POMC) Cocaine-and amphetamine-regulating transcrip (CART) Ghrelin, a hormone secreted when stomach is empty Peptide YY 3-36 (PYY3-36) is produced by the gut and is released into the circulation in response to food ingestion Y2R agonist is peptide YY3 36 (PYY3 36),