Bioactive compounds of Brazilian Regional fruits for treatment of metabolic diseases

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Bioactive compounds of Brazilian Regional fruits
for treatment of metabolic diseases
William Festuccia Institute of Biomedical
Sciences University of São Paulo,
Brazil william.festuccia_at_usp.br
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Presentation Outline

• Nutrient sensor mTOR as modulator of adiposity
  and inflammation

• Bioactive compounds of Brazilian and Quebec
  Regional fruits for treatment of metabolic
  diseases

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Disclosure

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

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First Law of Thermodynamics Energy can be
transformed, changed from one form to another,
but cannot be created or destroyed
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Diseases associated with Obesity
Idiopathic intracranial hypertension
Pulmonary disease abnormal function obstructive
sleep apnea hypoventilation syndrome
Stroke
Cataracts
Nonalcoholic fatty liver disease steatosis steatoh
epatitis 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
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Obesity over-supply of nutrients
Brain
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mTOR mechanistic target of rapamycin is the
catalytic core of 2 protein complexes
mTORC2
mTORC1
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GROWTH FACTORS
AMINO ACIDS GLUCOSE FATTY ACIDS
mTORC1
Protein Synthesis Lipid Synthesis Anaplerosis
Cell Size Proliferation Growth
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Leucine activates mTORC1 by inducing its
translocation to the lysosomes
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mTORC1 and 2 are activated by growth factors
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Adipose tissue mTORC1 is overactivated in obesity
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Is mTOR involved in the regulation of adiposity?
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Rapamycin inhibits mTORC1 and 2 in adipose tissue
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Chronic mTOR inhibition reduces adiposity
ADIPOCYTE DIAMETER
DNA CONTENT
RETRO MASS ( BW)
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Rapamycin reduces lipid incorporation and LPL
activity and expression in adipose tissue
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Rapamycin reduces mRNA levels of genes regulated
by PPARgamma
Rapamycin
Vehicle
PEPCK
FAT/CD36
FATP1
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Rapamycin reduces PPARgamma mRNA levels and DNA
binding activity
Rapamycin
Vehicle
DNA binding activity ( of control)
PPARgamma 1
PPARgamma 2
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mTORC1 modulates adiposity by affecting the
nuclear receptor PPARgamma
?
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Obesity chronic low-grade adipose tissue
inflammation
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Obesity induces macrophage polarization
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(No Transcript)
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Characterization of the macrophage mTORC2
deficiency mice model
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mTORC2 deficiency abolishes Akt activation by
Toll like receptor ligands in BMDM
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mTORC2 deficiency potentiates macrophage
polarization to M1 pro-inflammatory profile
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Myeloid cell mTORC2 deficiency decreases mice
survival upon acute LPS challenge
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Conclusion

• mTORC2 display anti-inflammatory actions on
  macrophages

Future Directions

• mTORC2 gain of function experiments
• mechanism underlying mTORC2 anti-inflammatory
  actions

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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
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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
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PHENOLIC COMPOUNDS POLYPHENOLS
Resveratrol
Naringenina
Elagic acid
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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

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Thank you!!!