PMID- 20876761
OWN - NLM
STAT- MEDLINE
DCOM- 20101228
LR  - 20220311
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 299
IP  - 6
DP  - 2010 Dec
TI  - Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, 
      and insulin signaling in L6 skeletal muscle cells: role of oxidative stress.
PG  - E1096-105
LID - 10.1152/ajpendo.00238.2010 [doi]
AB  - The type of free fatty acids (FFAs), saturated or unsaturated, is critical in the 
      development of insulin resistance (IR), since the degree of saturation correlates 
      with IR. We compared the effects of the saturated FFA palmitate, the unsaturated 
      FFA oleate, and a mixture of each on the production of mitochondrial reactive 
      oxygen species (mtROS), mitochondrial DNA (mtDNA) damage, mitochondrial function, 
      apoptosis, and insulin-signaling pathway in skeletal muscle cells. Only palmitate 
      caused a significant increase of mtROS production, which correlated with 
      concomitant mtDNA damage, mitochondrial dysfunction, induction of JNK, apoptosis, 
      and inhibition of insulin signaling. Blocking de novo synthesis of ceramide 
      abolished the effects of palmitate on mtROS production, viability, and insulin 
      signaling. Oleate alone did not cause mtROS generation and mtDNA damage, and its 
      addition to palmitate prevented palmitate-induced mtDNA damage, increased total 
      ATP levels and cell viability, and prevented palmitate-induced apoptosis and 
      inhibition of insulin-stimulated Akt (Ser(473)) phosphorylation. The peroxisome 
      proliferator activator receptor-gamma coactivator 1alpha (PGC-1alpha) protein level and 
      promoter activity were decreased at concentrations of palmitate >/=0.5 mM, whereas 
      addition of oleate increased both PGC-1alpha level and promoter activity. Expression 
      of the mitochondrial transcription factor (TFAM) was significantly diminished 
      after palmitate but not oleate treatment. Addition of the ROS scavenger, 
      N-acetylcystein (NAC), to palmitate restored both the expression and promoter 
      activity of PGC-1alpha as well as TFAM expression. We propose that 1) mtROS 
      generation is the initial event in the induction of mitochondrial dysfunction and 
      consequent apoptosis and the inhibition of insulin signaling and that 2) oleate 
      ameliorates palmitate-induced mitochondrial dysfunction and thus may contribute 
      to the prevention of palmitate-induced IR.
FAU - Yuzefovych, Larysa
AU  - Yuzefovych L
AD  - Dept. of Cell Biology and Neuroscience, Univ. of South Alabama, Mobile, AL 36688, 
      USA.
FAU - Wilson, Glenn
AU  - Wilson G
FAU - Rachek, Lyudmila
AU  - Rachek L
LA  - eng
GR  - DK-073808/DK/NIDDK NIH HHS/United States
GR  - ES-03456/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100928
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Insulin)
RN  - 0 (Reactive Oxygen Species)
RN  - 2UMI9U37CP (Oleic Acid)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Cell Count
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Mitochondria/*drug effects/metabolism
MH  - Muscle Fibers, Skeletal/*drug effects/metabolism
MH  - Nitric Oxide/metabolism
MH  - Oleic Acid/metabolism/*pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Palmitic Acid/metabolism/*pharmacology
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC3006254
EDAT- 2010/09/30 06:00
MHDA- 2010/12/29 06:00
PMCR- 2011/12/01
CRDT- 2010/09/30 06:00
PHST- 2010/09/30 06:00 [entrez]
PHST- 2010/09/30 06:00 [pubmed]
PHST- 2010/12/29 06:00 [medline]
PHST- 2011/12/01 00:00 [pmc-release]
AID - ajpendo.00238.2010 [pii]
AID - E-00238-2010 [pii]
AID - 10.1152/ajpendo.00238.2010 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1096-105. doi: 
      10.1152/ajpendo.00238.2010. Epub 2010 Sep 28.