Shabalina 2013 Abstract MiP2013
|Shabalina IG, Petrovic N, Kalinovich AV, Cannon B, Nedergaard J (2013) Comparative study of brown and white adipose tissue mitochondria in mice upon cold acclimation. Mitochondr Physiol Network 18.08.|
The ability of certain white adipose tissue depots to extensively increase relative expression levels of the gene for the uncoupling protein 1 (UCP1) has recently attracted considerable attention as potential anti-obesity treatment tool. The white adipose tissues and cells that display the ability to express UCP1 are presently referred as brite or beige . To date, studies of brite/beige adipose tissue have mostly focused on mRNA measurements, and the metabolic relevance of such expression may be questioned: Is UCP1 able to implement thermogenesis in brite/beige-fat mitochondria?
To examine the thermogenic properties of brite/beige adipose tissue and qualitatively relate these to those in classical brown adipose tissue, we exposed mice to thermoneutrality (30 °C; a thermogenically non-recruited state) or to cold conditions (4 °C) for about a month, i.e. until a new acclimation state had been achieved (a recruited state). We then dissected out the interscapular brown adipose tissue depot (IBAT) and the inguinal white adipose tissue depot (ingWAT) from these animals and isolated mitochondria in parallel from the dissected depots.
The mitochondrial preparation from non-recruited ingWAT was qualitatively different from IBAT mitochondria. The IBAT mitochondria showed UCP1-dependent thermogenesis (oxygen consumption) with canonical GDP sensitivity, high FCCP response and low phosphorylation capacity, whereas non-recruited ingWAT mitochondria exhibited no UCP1 activity and remarkable low oxidative capacity. In ingWAT mitochondria isolated from cold-acclimated mice, UCP1 protein levels increased almost to those of brown-fat mitochondria. The recruited ingWAT mitochondria showed UCP1-dependent oxygen consumption with both lipid or carbohydrate substrates and loss of thermogenesis in UCP1-KO mice. The levels of representative subunits of the respiratory Complexes CI-IV per mg mitochondrial protein were remarkably similar between the IBAT and ingWAT under recruited condition. Also phosphorylation capacity was similarly low in IBAT and ingWAT. Among many similarities there were several differences: The level of carnitine palmitoyl transferase I was significantly lower in ingWAT as compared to IBAT, and the level of glycerol-3 phosphate supported oxygen consumption was less than 50% of the level in IBAT. This may have implication concerning the necessity for reducing equivalent transfer in ingWAT. The difference between obesogenic C57Bl/6 and obesity-resistant 129Sv mouse strains was paralleled by a lower thermogenic potential in C57Bl/6 mitochondria.
Thus, recruited brite/beige-fat mitochondria-derived thermogenesis within inguinal white adipose tissue could be locally significant, especially in utilization of carbohydrate-derived substrates.
Labels: MiParea: Respiration, nDNA;cell genetics, Comparative MiP;environmental MiP Pathology: Obesity
Tissue;cell: Fat Preparation: Isolated mitochondria Enzyme: Uncoupling protein Regulation: Coupling efficiency;uncoupling Coupling state: OXPHOS, ET Pathway: Gp
Dept of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden. - Email: [email protected]
- Cannon B, Nedergaard J (2012) Neither brown nor white. Nature 488: 286-287.