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Metabolic Modifiers General Summary

Metabolic Modifiers General Summary. Lecture Outline. Somatotropin (bST, GH) What it is Mechanism  agonists What it is Mechanims Anabolic Steroids What are they How do the work CLA What it is Mechanism. Reasons for interest. Agriculture Maximize efficiency Feed the hungry

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Metabolic Modifiers General Summary

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  1. Metabolic ModifiersGeneral Summary

  2. Lecture Outline • Somatotropin (bST, GH) • What it is • Mechanism •  agonists • What it is • Mechanims • Anabolic Steroids • What are they • How do the work • CLA • What it is • Mechanism

  3. Reasons for interest • Agriculture • Maximize efficiency • Feed the hungry • Economic reasons • Dieting • Thin obsession • Athletics • Track and field • Baseball/football • Horseracing • Body Building

  4. Why Alter Metabolism? • Animal Agriculture • Leaner animal is more efficient • Consumers demand a leaner product • Improve energy balance •  Production,  Reproduction,  Metabolic Disorders • Design animal lipid with “healthy” fatty acid profile •  PUFA,  SFA,  Trans • Human Health • Obesity (60% of Americans are overweight or obese) • Hyperlipidemia • Atherosclerosis • High blood pressure • Diabetes • Cancer

  5. Somatotropin or Growth Hormone • Produced by the anterior pituitary • Protein hormone (~190 amino acids) • Approved in dairy cattle in 1994 • Causes: • During Growth • Increased protein synthesis • Decreased fat synthesis • During Lactation • Increased milk yield • Increase feed intake

  6. Somatotropin • Mechanism: Direct and indirect (mediated by IGF-1) • Lactation • Increases mammary cell activity • May increase mammary cell life span • Increase liver secretion of IGF-1 • Insulin like growth factor-1 (IGF-1): potent stimulator of cell growth • Growth: Depending upon EBAL • Increase protein synthesis • Decrease fat synthesis (lipogenesis) • Increase bone growth • Increase liver output of glucose (gluconeogenesis) • Increase liver secretion of IGF-I

  7. Pituitary Gland

  8. - HYPOTHALAMUS (Growth Hormone Releasing Factor, Somatostatin) Anterior Pituitary - GH Indirect Growth-Promoting Actions Direct Anti-Insulin Effects Liver and other organs Fat Carbohydrates (IGF) • Lipolysis ↓Lipogenesis ↓ Insulin Sensitivity Skeletal Extra-skeletal  chondrogenesis skeletal growth • protein synthesis  cell proliferation

  9. Somatotropin Problems

  10. Physiological Situation Circulating GH Milk kg ST-Treatment Up Up Genetically Superior Up Up Inadequate nutrition Up Down Poor Management Up Down Adequate Nutrition Moderate Undernutrition Severe Undernutrition Mammary Mammary Mammary IGF Complex IGF Complex Nutrient Pool Nutrient Pool Nutrient Pool ST ST ST + + + - - - Adipose Tissue Adipose Tissue Adipose Tissue *Adapted from Bauman and Vernon (1993)

  11. Somatotropin and Pig Growth Parameters

  12. Somatotropin Summary • Produced in Anterior pituitary gland • Protein hormone • Completely digested in GIT • Therefore must be injected • Causes increased growth and milk yield • Increase lean deposition and decrease fat • Most effects mediated by IGF-I • Commercially available (rbST) • Most intensely studied drug (human or animal) in the history of the pharmaceutical industry

  13. -agonists • Reasons for interest: • Human medicine • Branchodialators • Agriculture • Increase growth • Enhanced muscle • Decreased fat • Approved for pigs and cattle • Feed supplement • Orally active

  14. -agonists • Molecules that structurally resemble epinephrine • Caffeine, ephedrine, aspirin • Easily made in the lab • Muscle: • Increase in muscle synthesis • Decrease in muscle breakdown • Fat • Decrease in lipogenesis • Increase in lipolysis

  15. control 50 d/150.5 kg feed 100 kg /bw -agonist 46 d/132 kg feed 75 kg Ham 14.3 kg 13.3 kg Loin 11.2 10.7 Shoulders 11.9 11.2 Belly 10.2 10.3 Carcass lean 43.9 39.4 Moody et al., 2000

  16.  Agonist summary • Structurally resembles epinephrine • Increases muscle synthesis • Need to increase the protein % of diet • Decreases fat content • Orally active • Desensitization • Recently approved for pigs

  17. Steroids (Estrogens and Androgens) • Classification • Estrogenic • Androgenic • Predominate illegal steroid in humans • Progestin • Non-steroidal

  18. Steroids (Estrogens and Androgens) • Animal agriculture • Approved for beef • Not as effective in pigs • Effects • Increased protein accretion • Decreased fat accretion • Increased average daily gain • Increased feed efficiency

  19. Steroids (Estrogens and Androgens) • Mechanisms: not well understood • Mediated via somatotropin? • Increase ST/GH • Increase ST/GH receptors • Increase IGF-1 • Increase thyroid hormones

  20. Negative side effects (humans) • Both Genders • Increased heart disease, liver cancer, acne, male pattern baldness • Females: • Decreased breast size, deepening of voice, increase in body hair • Males: • reduced sperm production, shrinking of the testicles, impotence, difficulty or pain in urinating, baldness, and irreversible breast enlargement, testicular shrinking

  21. Steroid summary • Improves animal performance • Approved for beef cattle • Taken illegally by body builders • Used legally for many health reasons • Mechanism • Via ST/GH system

  22. Conjugated Linoleic Acid (CLA) • Many isomers (n=24) found in ruminant food products • C18:2cis-9, trans- 11 • C18:2trans-7, cis-9 • C18:2trans-10, cis-12 • C18:2cis-8, trans-10 • CLA has been shown to: • Anti-carcinogenic • Anti-atherogenic • Anti-diabetic • Enhanced immune system • Reduces severity of cachexia • Alleviates symptoms of lupus • Improved bone mineralization • Alters lipid metabolism t10, c12 CLA c9, t11 CLA c9, c12 C18:2

  23. CLA Effect During Growth • Adipose tissue metabolism • CLA supplement decreased body fat of mice by > 50 % (Park et al., 1997). • CLA supplements reduce body fat content of growing • Rats • Mice • Hamsters • Pigs • Dogs

  24. Effect of CLA on Body Fat in Growing Mice Adapted from Park et al., 1999

  25. Effect of Dietary CLA on Body Fat of Growing Gilts Dietary CLA, %Backfat Thickness, mm 0 21.0 0.125 17.1 0.250 16.1 0.500 16.9 0.750 15.4 1.000 14.6 White x Landrace gilts received dietary supplement of CLA for 8 weeks (final body weight 100-105 kg). Significant at P<0.024. Adapted from Ostrowska et al. 1999.

  26. CLA Effect During Growth • Lean tissue metabolism • CLA supplements increase protein percentage • Mice • Rats • Pigs

  27. Effect of CLA on Body Protein in Mice Adapted from Park et al., 1999

  28. Effects of CLA on Body Composition of Mice *Calculated by LHB 1Park et al 1997 2DeLany et al 1999

  29. CLA Products Available in “Health Stores”

  30. CLA Effect on Human Body Composition • No indication of increase in body lean • Studies showing decrease in body fat • Blankson et al., 2000 • Riserus et al., 2001 • Smedman et al., 2001 • Thom et al., 2001 • Studies showing no effect on body fat • Medina et al., 2000 • Zambell et al., 2000 • Atkins et al., 1999 Minor (3-6%)

  31. Potential Mechanisms •  Lipolysis •  Hormone sensitive lipase • Results are inconsistent with most showing no effect on plasma NEFA concentrations •  Lipogenesis • LPL activity; observed in many studies

  32. Conjugated linoleic acid summary • Naturally found in diet • Meat and milk • Decreases fat accretion • Decreases lipogenesis and increases lipolysis • No effect on protein metabolism • In experimental phase, not yet approved for animal agriculture

  33. Metabolic modifiers • Improve production • Increase protein synthesis • Decrease fat synthesis • Increase milk yield • Improve farm economics • Increased feed efficiency • Enhance human performance • Most studied molecules in pharmaceutical history • Animals supplemented with modifiers are completely safe to eat • Improving the efficiency of food (animal and plant) production is essential to feed the worlds growing population

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