R-α lipoic acid γ-cyclodextrin complex increases energy expenditure: a 4-month feeding study in mice.
OBJECTIVE
A high-fat diet (HFD) affects energy expenditure in laboratory rodents. R-α lipoic acid cyclodextrin (RALA-CD) complex is a stable form of lipoic acid (LA) and may improve energy expenditure. The aim of this study was to determine the effect of RALA-CD on energy expenditure and underlying molecular targets in female laboratory mice.


METHODS
Female C57BL/6J mice were fed a HFD containing 0.1% LA for about 16 wk. The effects on energy expenditure, gene and protein expression were assessed using indirect calorimetry, real-time reverse transcriptase polymerase chain reaction, and Western blot, respectively.


RESULTS
Supplementing mice with RALA-CD resulted in a significant increase in energy expenditure. However, both RALA per se (without γ-cyclodextrin) and S-α lipoic acid cyclodextrin did not significantly alter energy expenditure. Furthermore RALA-CD changed expression of genes encoding proteins centrally involved in energy metabolism. Transcriptional key regulators sirtuin 3 and peroxisome proliferator-activated receptor-γ, coactivator 1 alpha, as well as thyroid related enzyme type 2 iodothyronine deiodinase were up-regulated in brown adipose tissue (BAT) of RALA-CD-fed mice. Importantly, mRNA and/or protein expression of downstream effectors uncoupling protein (Ucp) 1 and 3 also were elevated in BAT from RALA-CD-supplemented mice.


CONCLUSION
Overall, present data suggest that RALA-CD is a regulator of energy expenditure in laboratory mice.
['Nikolai|Sibylle|S|', 'Huebbe|Patricia|P|', 'Metges|Cornelia C|CC|', 'Schloesser|Anke|A|', 'Dose|Janina|J|', 'Ikuta|Naoko|N|', 'Terao|Keiji|K|', 'Matsugo|Seiichi|S|', 'Rimbach|Gerald|G|']
D002001:Adipose Tissue, Brown D000818:Animals D002153:Calorimetry, Indirect D059305:Diet, High-Fat D004734:Energy Metabolism D005260:Female D007453:Iodide Peroxidase D007473:Ion Channels D051379:Mice D008810:Mice, Inbred C57BL D024101:Mitochondrial Proteins D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha D012333:RNA, Messenger D020133:Reverse Transcriptase Polymerase Chain Reaction D015398:Signal Transduction D056566:Sirtuin 3 D008063:Thioctic Acid D014157:Transcription Factors D000071256:Uncoupling Protein 1 D000071247:Uncoupling Protein 3 D015854:Up-Regulation D047408:gamma-Cyclodextrins
Lipoic acid γ-cyclodextrin Energy expenditure Mice Brown adipose tissue Uncoupling protein