Ando Adiponectin Presentation

8/19/2019 Ando Adiponectin Presentation

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Physiological Role andPhysiological Role and

Molecular MechanismMolecular Mechanismof Adiponectinof Adiponectin

Yumi AndoYumi Ando

Pomona CollegePomona College

Advanced Biochemistry Advanced Biochemistry


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What is Adiponectin??

hat is Adiponectin??

A signaling molecule that is secreted A signaling molecule that is secreted

from white and brown adipose tissue.from white and brown adipose tissue.

Composed of 247 amino acids.Composed of 247 amino acids.

Accounts for .! " of total serum Accounts for .! " of total serum

protein.protein.

Concentration#Concentration# 2$2 %g&m' in the blood2$2 %g&m' in the blood


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Aside: Adipose Tissue

side: Adipose Tissue

Adipose tissue stores ( releases energy in the Adipose tissue stores ( releases energy in theform of )A* and free fatty acids+ respectively.form of )A* and free fatty acids+ respectively.

,-/0/1+ it is also gaining recognition as an,-/0/1+ it is also gaining recognition as anendocrine organ that secretes proteins w&endocrine organ that secretes proteins w& proproinflammatory effects+ as well as metabolicinflammatory effects+ as well as metaboliceffects.effects.

)hese proteins are called 3adipocytoines5 or)hese proteins are called 3adipocytoines5 or3adipoines53adipoines5

/6amples# adiponectin+ leptin+ resistin./6amples# adiponectin+ leptin+ resistin.


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Structure of adiponectin

tructure of adiponectin

domains# Collagenlie domain+ globular domains# Collagenlie domain+ globular

domain+ and a signal se8uence.domain+ and a signal se8uence.

)aen from 9adowai

and Yamauchi+ 24


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:orm homomultimers:orm homomultimers

main oligomeric main oligomeric

forms# ';+ ;;+forms# ';+ ;;+

and ,;and ,;

-ligomeri


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Two forms, two different

wo forms, two different

functions?unctions?

Adiponectin can e6ist as a Adiponectin can e6ist as a fulllengthfulllength protein or as aprotein or as a globular globular form byform by

undergoing proteolytic cleavage+ whichundergoing proteolytic cleavage+ whichleaves only the globular head domainleaves only the globular head domainintact.intact.

)he globular form of adiponectin appears)he globular form of adiponectin appears

to stimulate > o6idation in muscle+ whileto stimulate > o6idation in muscle+ whilethe fulllength form appears to decreasethe fulllength form appears to decreaseglucose output by the liverglucose output by the liver


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Genetic actors

enetic actors

)he gene for adiponectin is located on)he gene for adiponectin is located on

chromosome 827.chromosome 827.

)his region of the chromosome has also been)his region of the chromosome has also beenlined to type 2 diabetes.lined to type 2 diabetes.

A ?@P located 27 base pairs downstream of A ?@P located 27 base pairs downstream of

the start site of the adiponectin gene wasthe start site of the adiponectin gene was

associated with increased insulin resistanceassociated with increased insulin resistanceand ris of developing type 2 diabetes.and ris of developing type 2 diabetes.


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Why is it important to

hy is it important to

study adiponectin?tudy adiponectin?

/vidence strongly suggests that adiponectin/vidence strongly suggests that adiponectinplays a role in the pathophysiology of type 2plays a role in the pathophysiology of type 2diabetes and other metabolic syndromediabetes and other metabolic syndromediseasesdiseases


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n a study conducted by ,otta et al.+n a study conducted by ,otta et al.+

D2EF+D2EF+ plasma adiponectin levelsplasma adiponectin levels

dropped in parallel to the observation ofdropped in parallel to the observation ofdecreased insulin sensitivity in rhesusdecreased insulin sensitivity in rhesus

moneys.moneys.

;oneys w& decreased insulin sensitivity;oneys w& decreased insulin sensitivity

developed type 2 diabetes.developed type 2 diabetes.


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Molecular Mec anism of

olecular Mec anism of

Adiponectin

diponectin

A study conducted by A study conducted byYamauchi et al.Yamauchi et al.D2EF showed thatD2EF showed thatadiponectinadiponectinstimulates glucosestimulates glucoseutili


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Adiponectin Receptors

diponectin Receptors

)here are two nown ones#)here are two nown ones# Adipo1E and Adipo12. Adipo1E and Adipo12.

)hey are integral membrane proteins that have seven)hey are integral membrane proteins that have seventransmembrane domains where the @ terminus istransmembrane domains where the @ terminus is

located within the cell+ and the C terminus is e6ternal.located within the cell+ and the C terminus is e6ternal. Adipo1E is a receptor that mainly binds globular Adipo1E is a receptor that mainly binds globular

adiponectin+ while Adipo12 binds to fulllengthadiponectin+ while Adipo12 binds to fulllengthadiponectinadiponectin

Adipo1E is abundant in seletal muscle. -n the other Adipo1E is abundant in seletal muscle. -n the otherhand+ Adipo12 is most e6pressed in the liver.hand+ Adipo12 is most e6pressed in the liver.


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ossi"le therapeutic

ossi"le therapeutic

strategies#

trategies#

methods have been studied. methods have been studied.

Gpregulation of adiponectinGpregulation of adiponectin

Gpregulation of adiponectin receptorsGpregulation of adiponectin receptors

Hevelopment of adiponectin receptorHevelopment of adiponectin receptor

agonistsagonists


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$smotin

smotin

potential agonist for adiponectinpotential agonist for adiponectin

t is a plant protein that is implicated int is a plant protein that is implicated in

the plant defense system. Causesthe plant defense system. Causesapoptosis in yeast.apoptosis in yeast.

adiponectin and osmotin were able toadiponectin and osmotin were able to

induce phosphorylation of A;P inase ininduce phosphorylation of A;P inase inC2CE2 myocytes.C2CE2 myocytes.


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% things to remem"er#

things to remem"er#

adiponectin is a potent insulin sensiti


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References

eferences

Cnop ;. et al. D2F 1elationship of adiponectin to body fat distribution+ insulin sensitivity and plasma lipoproteins# evidence forCnop ;. et al. D2F 1elationship of adiponectin to body fat distribution+ insulin sensitivity and plasma lipoproteins# evidence forindependent roles of age and se6.independent roles of age and se6. Diabetologia.Diabetologia. 4# 4!=I4=.4# 4!=I4=.

:asshauer ;.+ Pasche 1.+ and ?tumvoll+ ;. D24F Adiponectin+ obesity+ and cardiovascular disease.:asshauer ;.+ Pasche 1.+ and ?tumvoll+ ;. D24F Adiponectin+ obesity+ and cardiovascular disease. Biochimie.Biochimie. J# 77=7J4.J# 77=7J4. 'ihn A.?.+ Pedersen ?.B.+ and 1ichelsen B. D24F Adiponectin# action+ regulation+ and association to insulin sensitivity.'ihn A.?.+ Pedersen ?.B.+ and 1ichelsen B. D24F Adiponectin# action+ regulation+ and association to insulin sensitivity. ObesityObesity

Reviews.Reviews. # E2E.# E2E. :ruebis K. et al. D2EF:ruebis K. et al. D2EF Proteolytic cleavage product of Ha adipocyte complementrelated protein increases fatty acid o6idation inProteolytic cleavage product of Ha adipocyte complementrelated protein increases fatty acid o6idation in

muscle and causes weight loss in mice.muscle and causes weight loss in mice. Proc Natl Acad Sci USA.Proc Natl Acad Sci USA. =J# 2!2E.=J# 2!2E. ,ara 9.+ et al. D22F *enetic variation in the gene encoding adiponectin is associated with an increased ris of type 2 diabetes in the,ara 9.+ et al. D22F *enetic variation in the gene encoding adiponectin is associated with an increased ris of type 2 diabetes in the

Kapanese population.Kapanese population. DiabetesDiabetes. !E#!I!4.. !E#!I!4. ,otta 9.+ et al. D2EF Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin,otta 9.+ et al. D2EF Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin

sensitivity during the progression to type 2 diabetes in rhesus moneys.sensitivity during the progression to type 2 diabetes in rhesus moneys. DiabetesDiabetes. !#EE2IEE. !#EE2IEE 9adowai ).+ and Yamauchi ). D2!F Adiponectin and Adiponectin 1eceptors.9adowai ).+ and Yamauchi ). D2!F Adiponectin and Adiponectin 1eceptors. Endocrine Reviews.Endocrine Reviews. 2DF# 4=4!E.2DF# 4=4!E. 9adowai ). et al.D2F Adiponectin and adiponectin receptors in insulin resistance+ diabetes+ and the metabolic syndrome.9adowai ). et al.D2F Adiponectin and adiponectin receptors in insulin resistance+ diabetes+ and the metabolic syndrome. JornalJornal

o! "linical #nvestigation.o! "linical #nvestigation. EED7F# E7J4E7=2.EED7F# E7J4E7=2. 9ubota @.+ et al. D2F Pioglita

Ando Adiponectin Presentation

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