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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