PMID- 20015518
OWN - NLM
STAT- MEDLINE
DCOM- 20100617
LR  - 20220321
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 59
IP  - 7
DP  - 2010 Jul
TI  - alpha-Lipoic acid increases energy expenditure by enhancing adenosine 
      monophosphate-activated protein kinase-peroxisome proliferator-activated 
      receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice.
PG  - 967-76
LID - 10.1016/j.metabol.2009.10.018 [doi]
AB  - Skeletal muscle mitochondrial dysfunction is associated with aging and diabetes, 
      which decreases respiratory capacity and increases reactive oxygen species. 
      Lipoic acid (LA) possesses antioxidative and antidiabetic properties. Metabolic 
      action of LA is mediated by activation of adenosine monophosphate-activated 
      protein kinase (AMPK), a cellular energy sensor that can regulate peroxisome 
      proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), a master 
      regulator of mitochondrial biogenesis. We hypothesized that LA improves energy 
      metabolism and mitochondrial biogenesis by enhancing AMPK-PGC-1alpha signaling in 
      the skeletal muscle of aged mice. C57BL/6 mice (24 months old, male) were 
      supplemented with or without alpha-LA (0.75% in drinking water) for 1 month. In 
      addition, metabolic action and cellular signaling of LA were studied in cultured 
      mouse myoblastoma C2C12 cells. Lipoic acid supplementation improved body 
      composition, glucose tolerance, and energy expenditure in the aged mice. Lipoic 
      acid increased skeletal muscle mitochondrial biogenesis with increased 
      phosphorylation of AMPK and messenger RNA expression of PGC-1alpha and glucose 
      transporter-4. Besides body fat mass, LA decreased lean mass and attenuated 
      phosphorylation of mammalian target of rapamycin (mTOR) signaling in the skeletal 
      muscle. In cultured C2C12 cells, LA increased glucose uptake and palmitate 
      beta-oxidation, but decreased protein synthesis, which was associated with 
      increased phosphorylation of AMPK and expression of PGC-1alpha and glucose 
      transporter-4, and attenuated phosphorylation of mTOR and p70S6 kinase. We 
      conclude that LA improves skeletal muscle energy metabolism in the aged mouse 
      possibly through enhancing AMPK-PGC-1alpha-mediated mitochondrial biogenesis and 
      function. Moreover, LA increases lean mass loss possibly by suppressing protein 
      synthesis in the skeletal muscle by down-regulating the mTOR signaling pathway. 
      Thus, LA may be a promising supplement for treatment of obesity and/or insulin 
      resistance in older patients.
FAU - Wang, Yi
AU  - Wang Y
AD  - State Key Laboratory of Animal Nutrition, College of Animal Science and 
      Technology, China Agricultural University, Beijing, China.
FAU - Li, Xiaojie
AU  - Li X
FAU - Guo, Yuming
AU  - Guo Y
FAU - Chan, Lawrence
AU  - Chan L
FAU - Guan, Xinfu
AU  - Guan X
LA  - eng
GR  - R03 DK084125/DK/NIDDK NIH HHS/United States
GR  - R01 HL051586/HL/NHLBI NIH HHS/United States
GR  - HL51586/HL/NHLBI NIH HHS/United States
GR  - K01 DK075489-04S1/DK/NIDDK NIH HHS/United States
GR  - K01 DK075489-04/DK/NIDDK NIH HHS/United States
GR  - R01 HL051586-12/HL/NHLBI NIH HHS/United States
GR  - K01 DK075489/DK/NIDDK NIH HHS/United States
GR  - R03 DK084125-02/DK/NIDDK NIH HHS/United States
GR  - K01 DK075489-01/DK/NIDDK NIH HHS/United States
GR  - 5K01DK75489/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20091216
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Antioxidants)
RN  - 0 (Fatty Acids)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - 63231-63-0 (RNA)
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Blotting, Western
MH  - Body Composition/drug effects
MH  - Calorimetry, Indirect
MH  - Cell Line
MH  - Cyclic AMP-Dependent Protein Kinases/*physiology
MH  - Deoxyglucose/metabolism
MH  - Energy Metabolism/*drug effects
MH  - Fatty Acids/metabolism
MH  - Glucose Tolerance Test
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria, Muscle/drug effects/metabolism
MH  - Muscle, Skeletal/enzymology/*metabolism
MH  - Oxidation-Reduction
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Phenylalanine/metabolism
MH  - RNA/biosynthesis/isolation & purification
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - Thioctic Acid/*pharmacology
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors
PMC - PMC2882509
MID - NIHMS166156
COIS- Conflicts of interest: The authors declare that there are no conflicts of 
      interest associated with this manuscript.
EDAT- 2009/12/18 06:00
MHDA- 2010/06/18 06:00
PMCR- 2011/07/01
CRDT- 2009/12/18 06:00
PHST- 2009/05/28 00:00 [received]
PHST- 2009/10/20 00:00 [revised]
PHST- 2009/10/21 00:00 [accepted]
PHST- 2009/12/18 06:00 [entrez]
PHST- 2009/12/18 06:00 [pubmed]
PHST- 2010/06/18 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - S0026-0495(09)00449-1 [pii]
AID - 10.1016/j.metabol.2009.10.018 [doi]
PST - ppublish
SO  - Metabolism. 2010 Jul;59(7):967-76. doi: 10.1016/j.metabol.2009.10.018. Epub 2009 
      Dec 16.