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Bioactive compounds of Brazilian Regional fruits for treatment of metabolic diseases

Bioactive compounds of Brazilian Regional fruits for treatment of metabolic diseases. William Festuccia Institute of Biomedical Sciences University of São Paulo, Brazil william.festuccia@usp.br. Presentation Outline. Nutrient sensor mTOR as modulator of adiposity and inflammation.

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Bioactive compounds of Brazilian Regional fruits for treatment of metabolic diseases

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  1. Bioactive compounds of Brazilian Regional fruits for treatment of metabolic diseases William Festuccia Institute of Biomedical Sciences University of São Paulo, Brazil william.festuccia@usp.br

  2. Presentation Outline • Nutrient sensor mTOR as modulator of adiposity and inflammation • Bioactive compounds of Brazilian and Quebec Regional fruits for treatment of metabolic diseases

  3. Disclosure • I have no actual or potential conflict of interest in relation to this presentation.

  4. First Law of Thermodynamics Energy can be transformed, changed from one form to another, but cannot be created or destroyed

  5. Diseases associated with Obesity Idiopathic intracranial hypertension Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Stroke Cataracts Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Coronary heart disease Diabetes Dyslipidemia Hypertension Severe pancreatitis Gall bladder disease Cancer breast, uterus, cervix colon, esophagus, pancreas kidney, prostate Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Osteoarthritis Phlebitis venous stasis Skin Gout

  6. Obesity: over-supply of nutrients Brain Adipose tissue Fatty acids Amino acids Glucose Muscle Pancreas Liver

  7. mTOR: mechanistic target of rapamycin is the catalytic core of 2 protein complexes mTORC2 mTORC1

  8. GROWTH FACTORS AMINO ACIDS GLUCOSE FATTY ACIDS mTORC1 Protein Synthesis Lipid Synthesis Anaplerosis Cell Size Proliferation Growth ? Obesity fat cell size & number

  9. Leucine activates mTORC1 by inducing its translocation to the lysosomes

  10. mTORC1 and 2 are activated by growth factors

  11. Adipose tissue mTORC1 is overactivated in obesity

  12. Is mTOR involved in the regulation of adiposity?

  13. Rapamycin inhibits mTORC1 and 2 in adipose tissue

  14. Chronic mTOR inhibition reduces adiposity ADIPOCYTE DIAMETER DNA CONTENT RETRO MASS (% BW)

  15. Rapamycin reduces lipid incorporation and LPL activity and expression in adipose tissue

  16. Rapamycin reduces mRNA levels of genes regulated by PPARgamma LIPIN 1 Rapamycin Vehicle PEPCK FAT/CD36 FATP1

  17. Rapamycin reduces PPARgamma mRNA levels and DNA binding activity Rapamycin Vehicle DNA binding activity (% of control) PPARgamma 1 PPARgamma 2

  18. PPARγ RXR mTORC1 modulates adiposity by affecting the nuclear receptor PPARgamma mTORC1 ? +

  19. Obesity: chronic low-grade adipose tissue inflammation

  20. Obesity induces macrophage polarization

  21. TNFα, LPS TLR4 X Cre-Lox System AKT/PKB

  22. Characterization of the macrophage mTORC2 deficiency mice model

  23. mTORC2 deficiency abolishes Akt activation by Toll like receptor ligands in BMDM

  24. mTORC2 deficiency potentiates macrophage polarization to M1 pro-inflammatory profile

  25. Myeloid cell mTORC2 deficiency decreases mice survival upon acute LPS challenge

  26. Conclusion • mTORC2 display anti-inflammatory actions on macrophages Future Directions • mTORC2 gain of function experiments • mechanism underlying mTORC2 anti-inflammatory actions

  27. Screening of Quebec and Brazilian fruits aiming to identify bioactive molecules to prevent and treat obesity and type 2 diabetes Quebec Institute of Cardiology School of Pharmacy Dr André Marette Dr Franco M Lajolo

  28. FRUITS AND VEGETABLES vs TYPE 2 DIABETES 90% of T2D cases are preventable by lifestyle modifications such as consuming a diet rich in fruits and vegetables. Willett WC, Science, 2002 Lindström J et al., Lancet, 2006 World Health Organization Consumption of fruits is inversely correlated with T2D prevalence Low fruit and vegetable intake is among the top 10 selected risk factors for global mortality A minimum of 400g of fruit and vegetables per day for the prevention of chronic diseases

  29. PHENOLIC COMPOUNDS: POLYPHENOLS Resveratrol Naringenina Elagic acid

  30. Acknowledgments Quebec Institute of Cardiology – Laval University • André Marette • Yves Deshaies • Fernando Forato Anhê • Genevieve Pilon • Mat Laplante • Pierre-Gilles Blanchard • Institute of Nutraceutical and Functional Food – Laval University • Yves Desjardins Institute of Biomedical Sciences, USP • Juliana Magdalon • Vivian Paschoal • Thiago Belchior • Patricia Chimin • Alex Shimura School of Pharmacy - USP • Franco Lajolo • Maria Inés Genovese • Marcela Roquim • Helena Barros

  31. Thank you!!!

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