R-α lipoic acid γ-cyclodextrin complex increases energy expenditure: a 4-month feeding study in mice

Nutrition. 2014 Feb;30(2):228-33. doi: 10.1016/j.nut.2013.08.002.

Abstract

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.

Keywords: Brown adipose tissue; Energy expenditure; Lipoic acid; Mice; Uncoupling protein; γ-cyclodextrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Calorimetry, Indirect
  • Diet, High-Fat
  • Energy Metabolism / drug effects*
  • Female
  • Iodide Peroxidase / genetics
  • Iodide Peroxidase / metabolism
  • Iodothyronine Deiodinase Type II
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism
  • Thioctic Acid / pharmacology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Uncoupling Protein 1
  • Uncoupling Protein 3
  • Up-Regulation
  • gamma-Cyclodextrins / pharmacology*

Substances

  • Ion Channels
  • Mitochondrial Proteins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • RNA, Messenger
  • Sirt3 protein, mouse
  • Transcription Factors
  • UCP1 protein, human
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Uncoupling Protein 3
  • gamma-Cyclodextrins
  • Thioctic Acid
  • Iodide Peroxidase
  • Sirtuin 3
  • gamma-cyclodextrin