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WEBINAR Nutrition, metabolism , and bone remodeling

WEBINAR Nutrition, metabolism , and bone remodeling. Gérard Friedlander , MD, PhD. Adipokines. How does leptin affect bone mass?. Pre-osteoblasts. Monocytes. Osteoblasts. Osteoclasts. Osteocytes. Adipocyte. Pre-osteoblasts. Monocytes. Osteoblasts. Osteoclasts. Osteocytes.

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WEBINAR Nutrition, metabolism , and bone remodeling

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  1. WEBINARNutrition, metabolism, and boneremodeling Gérard Friedlander, MD, PhD

  2. Adipokines

  3. How doesleptin affect bone mass?

  4. Pre-osteoblasts Monocytes Osteoblasts Osteoclasts Osteocytes Adipocyte

  5. Pre-osteoblasts Monocytes Osteoblasts Osteoclasts Osteocytes Adipocyte Leptin

  6. Adipocyte Leptin Osteoblasts Pre-osteoblasts Monocytes Osteoclasts Osteocytes

  7. Pre-osteoblasts Monocytes Osteoblasts Osteoclasts Osteocytes Adipocyte Leptin ? ?

  8. Pre-osteoblasts Monocytes Osteoblasts Osteoclasts Osteocytes Adipocyte Leptin

  9. Pre-osteoblasts Monocytes Osteoblasts Osteoclasts Osteocytes Adipocyte Leptin

  10. Pre-osteoblasts Monocytes Osteoblasts Osteoclasts Osteocytes Adipocyte Leptin

  11. Leptinmodulatesbone resorption

  12. Adipocyte Leptin Hypothalamus Sympathetic nervous system Osteoblast Adrenergic receptor

  13. Adipocyte Leptin Hypothalamus Sympathetic nervous system Osteoblast Adrenergic receptor RANKL

  14. Adipocyte Leptin Hypothalamus Sympathetic nervous system Osteoblast Adrenergic receptor RANK RANKL Osteoclast Osteoclast precursor

  15. Adipocyte Leptin CART Hypothalamus Sympathetic nervous system Osteoblast Adrenergic receptor RANK - RANKL Osteoclast Osteoclast precursor

  16. Adipocyte Leptin CART Hypothalamus Sympathetic nervous system Osteoblast Adrenergic receptor RANK - + - RANKL Osteoclast Osteoclast precursor

  17. Adiponectin is associated with lower bone mass in childhood

  18. Adiponectin Adipocytes

  19. Adiponectin Osteoblast Adipocytes

  20. Adiponectin Osteoblast Adipocytes

  21. Adiponectin Osteoblast Adipocytes

  22. Adipokines and the risk of fracture in older adults

  23. Bone marrow stem cell Adiponectin Leptin Osteoblasts differentiation Osteoclasts differentiation Bone formation Bone resorption

  24. Bone marrow stem cell Adiponectin Leptin Osteoblasts differentiation Osteoclasts differentiation Bone formation Bone resorption Low serum leptin High serum adiponectin Associated with fracture risk ?

  25. Bone marrow stem cell Adiponectin Leptin Osteoblasts differentiation Osteoclasts differentiation Bone formation Bone resorption Low serum leptin High serum adiponectin Associated with fracture risk ? Women : N =1478 Age : 73,5 Men : N =1568 Age : 73,8 No associated risk increase No associated risk increase Low serum leptin No associated risk increase 94% risk increase compare to low serum concentration High serum adiponectin

  26. Influence of Adipokines and Ghrelin on bone mineral density and fracture risk

  27. Adiponectin Regulate inflammatory pathways, promote bone resorbption Leptin Regulate appetite, weight, promote bone proliferation Ghrelin Increase fat mass and appetite

  28. Adiponectin Regulate inflammatory pathways, promote bone resorbption Leptin Regulate appetite, weight, promote bone proliferation Ghrelin Increase fat mass and appetite (independent of gender, menopausal status and fat mass) High Adiponectin serum concetration No association withGhrelinserum concentration Low Bone Mineral Density High Bone Mineral Density Particularly significant for post menopausal women) High Leptin serum concentration

  29. Adiponectin Regulate inflammatory pathways, promote bone resorbption Leptin Regulate appetite, weight, promote bone proliferation Ghrelin Increase fat mass and appetite (independent of gender, menopausal status and fat mass) High Adiponectin serum concetration No association withGhrelinserum concentration Low Bone Mineral Density High Bone Mineral Density Particularly significant for post menopausal women) High Leptin serum concentration Potentially for vertebral fracture in man only High Adiponectin serum concetration

  30. Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation

  31. Adipocytes bFGF Fat tissue FGFR1 + PI3K Pre-osteoblast

  32. Adipocytes Pre-osteoblasts bFGF Pre-osteoblast proliferation Fat tissue + FGFR1 + PI3K Osteoblast differentiation Osteoblasts Pre-osteoblast

  33. Adipocytes Pre-osteoblasts bFGF Pre-osteoblast proliferation Fat tissue + FGFR1 + PI3K Osteoblast differentiation + OPG - Osteoblasts RANKL Pre-osteoblast

  34. Adipocytes Pre-osteoblasts bFGF Pre-osteoblast proliferation Fat tissue + FGFR1 + PI3K Osteoblast differentiation + OPG - Osteoblasts RANKL Pre-osteoblast OPG RANKL - Osteoclasts Osteoclast differentiation Pre-osteoclast

  35. High serum adiponectin predicts incident fractures in elderly men

  36. Pre-Osteoblasts Osteoclast progenitor + Osteoblasts RANKL + Osteoclasts Adiponectin Bone resorption Bone formation Adipocyte N = 999 Average age : 75 years old Average follow-up : 5,2 years No fracture N=849 At least one fracture N=150 Hip BMD : 0,97 g/cm2 0,90 g/cm2

  37. Pre-Osteoblasts Osteoclast progenitor + Osteoblasts RANKL + Osteoclasts Adiponectin Bone resorption Bone formation

  38. Pre-Osteoblasts Osteoclast progenitor + Osteoblasts RANKL + Osteoclasts Adiponectin Bone resorption Bone formation Adipocyte N = 999 Average age : 75 years old Average follow-up : 5,2 years No fracture N=849 At least one fracture N=150 Hip BMD : 0,97 g/cm2 0,90 g/cm2 + 30% increase risk of fracture Serum adiponectin 11,5 mg/mL 14,2 mg/mL

  39. Dietary fat

  40. Short-term exposure to low-carbohydrate, high-fat diet induces low bone mineral density and reduces bone formation in rats

  41. IGF-I

  42. Modulation of osteoclastogenesis by fatty acids

  43. Osteoclasts Saturated fatty acid

  44. Osteoclasts Saturated fatty acid

  45. Metabolic syndrome and bone health in older men and women

  46. Abdominal Obesity High Triglycerides Low HDL Cholesterol Hypertension Hyperglycemia Metabolic syndrome

  47. Abdominal Obesity High Triglycerides Low HDL Cholesterol Hypertension Hyperglycemia Aging Genetics Metabolic syndrome Lifestyle Release of cytokines Insulin resistance

  48. Abdominal Obesity High Triglycerides Low HDL Cholesterol Hypertension Hyperglycemia Aging Genetics Metabolic syndrome Lifestyle Release of cytokines Insulin resistance

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