Effect of short-term free Fatty acids elevation on mitochondrial function in skeletal muscle of healthy individuals.
BACKGROUND
Mitochondrial dysfunction has been proposed as an underlying mechanism in the pathogenesis of insulin resistance and type 2 diabetes mellitus.


OBJECTIVE
To determine whether mitochondrial dysfunction plays a role in the free fatty acid (FFA)-induced impairment in insulin action in skeletal muscle of healthy subjects.


METHODS
Eleven lean normal glucose tolerant individuals received 8 h lipid and saline infusion on separate days with a euglycemic insulin clamp during the last 2 h. Vastus lateralis muscle biopsies were performed at baseline and after 6 h lipid or saline infusion. Inner mitochondrial membrane potential (Psi(m)) and mitochondrial mass were determined ex vivo by confocal microscopy.


RESULTS
Compared with saline infusion, lipid infusion reduced whole-body glucose uptake by 22% (P < 0.05). Psi(m) decreased by 33% (P < 0.005) after lipid infusion and the decrement in Psi(m) correlated with change in plasma FFA after lipid infusion (r = 0.753; P < 0.005). Mitochondrial content and morphology did not change after lipid infusion. No significant changes in genes expression, citrate synthase activity, and total ATP content were observed after either lipid or saline infusion.


CONCLUSIONS
Short-term physiological increase in plasma FFA concentration in lean normal glucose tolerant subjects induces insulin resistance and impairs mitochondrial membrane potential but has no significant effects on mitochondrial content, gene expression, ATP content, or citrate synthase activity.
Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, Texas 78229, USA.
Alberto O
AO
Chavez
Subhash
S
Kamath
Rucha
R
Jani
Lokendra K
LK
Sharma
Adriana
A
Monroy
Muhammad A
MA
Abdul-Ghani
Victoria E
VE
Centonze
Padma
P
Sathyanarayana
Dawn K
DK
Coletta
Cristopher P
CP
Jenkinson
Yidong
Y
Bai
Franco
F
Folli
Ralph A
RA
Defronzo
Devjit
D
Tripathy
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006262:Health; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids; D000255:Adenosine Triphosphate; D002950:Citrate (si)-Synthase; D005947:Glucose