The Vicious Circle of the Metabolic Cycle

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 The Vicious Circle of theMetabolic Cycle

Ian R. Lanza, Ph.D.

Associate Professor of MedicineDivision of ndocrinolo!y

Mayo Clinic Colle!e of Medicine

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2014 Prevalence of Self-ReportedObesity Among U.S. Adlts

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"u#an Po$ulation Mi!ration

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ner!y %alance

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&hen en!ineerin! fails us

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"e$atic vein

to !eneralcirculation

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Adi Cohen, Colu#bia'niversity

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(at inside #uscles

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(at inside #uscles

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(at inside #uscles

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ner!etically)de#andin!$rocesses in s*eletal #uscle

• Re$olarization +a-/ - ATPase0

• Calciu# trans$ort +Ca1-

ATPase0• Crossbrid!e cyclin! +Myosin

ATPase0

2334

increase inATP de#and

5yet a#azin!ly, ATP concentrations

re#ain constant in #uscle durin! hi!h)

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"o6 to $revent e7uilibriu#8

!acrontrients"

Carbohydrate(at

Protein

(atty acidsA#ino acids

Monosaccharides

Digestion

#omple$ componds9lyco!en

 Tri!lyceridesProteins

 Anabolism(requiresenergy)

Catabolism(releasesenergy)

Simple compondsC:1"1:

";

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 The Mitochondrion

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Cardiac #uscle

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:4idativePhos$horylation

+Cellular Res$iration0• 9enerates =>? of our ATP• ADP $hos$horylated as electrons

#ove fro# fuels to o4y!en

%lectronsorces

C":

(atty acids/etones

A#ino Acids

:4y!en

"1:

C@"21:@ - @:1 @C:1 - @"1: - ;@ ATP RR@@2 P:;@

+@B10;.3

C2@";1:1 - 1;:1 2@C:1 - 2@"1: - 21 ATP RR2@1;3.P:21 2@B1 1.=

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Pal#itate+2@E30

Linoleic acid+2=E10

icosa$entaenoic acid

+13E>0

Li$id Metabolis#

 Tri!lyceride

!lycerol esteriFed fattyacids

(ree fatty acids

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(at stora!e

Adi$ocytesin adi$ose

tissue

Dro$lets inliver

+ecto$ic0

Dro$lets in#uscle

+ecto$ic0

9ood$aster et al., JCEM, 1Mohl*e, Nature Genetics, 133=

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Li$olysisE brea*in! do6n tri!lycerides

 Tri!lycerides Di!lycerides Mono!lycerides 9lycerol

"

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 The Vicious Cycleutritional

e4cess

:4idative

stress

Protein GDA

da#a!e

Decrease$rotein7uality

Cell death

Dysfunctional

#itochondria

I#$aired

#uscle function

4erciseintolerance

Physical

inactivity

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ner!y %alance

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%ody fat Hset $oint

Le$ti

n

Decreased

a$$etite

IncreasedR

obob#ice

dbdb#ice

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"einonen et al.,

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