miRNA profiling of human brown adipose tissue and brown adipocyte progenitor cells — ASN Events

miRNA profiling of human brown adipose tissue and brown adipocyte progenitor cells (#55)

Aaron Russell 1 , Isabelle Guller 1
  1. School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC, Australia

 Brown adipose tissue (BAT) is present in most mammals and controls cold-induced and diet-induced thermogenesis. In rodents, BAT activation generates heat, dissipates excess energy and is required for survival. BAT is therefore considered a potential therapeutic target to increase energy expenditure (EE) and fight obesity. Until recently it has been thought that humans were devoid of functional BAT, questioning the relevance of rodent BAT metabolism to human obesity. However, the use of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has revealed the presence of active depots of BAT in adult humans1-6. This has renewed scientific interest in understanding human BAT activation. BAT shares a common origin with skeletal muscle, supporting their common role in regulating metabolism and energy expenditure7. Human skeletal muscle-derived CD34+ brown adipocyte progenitor cells have also been identified8. These cells have increased uncoupled oxidative phosphorylation in vitro8 and an altered expression profile in obese patients9; they may potentially be another target to increase EE. The molecular mechanisms regulating human BAT and CD34+ brown adipocyte progenitor cells are not well established. MicroRNAs (miRNAs) are small regulatory molecules that regulate gene networks via their inhibition of protein translation or messenger RNA degradation10,11. A suite of mouse BAT-enriched miRNAs have been identified and several miRNA species can influence mouse brown adipocyte development in vitro12 13; whether these observations translate to human BAT is unknown. Here we present the miRNA profile of human BAT and differentiated human CD34+ brown adipocyte progenitor cells. Bioinformatics analysis has been used to identify miRNAs potentially involved human BAT development and function.  

  1. Cypess, A. M. et al. Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360, 1509-1517, 2009.
  2. Saito, M. et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58, 1526-1531, 2009.
  3. van Marken Lichtenbelt, W. D. et al. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 360, 1500-1508, 2009.
  4. Virtanen, K. A. et al. Functional brown adipose tissue in healthy adults. N. Engl. J. Med. 360, 1518-1525, 2009.
  5. Zingaretti, M. C. et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 23, 3113-3120, 2009
  6. Nedergaard, J., Bengtsson, T. & Cannon, B. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab. 293, E444-452, 2007.
  7. Timmons, J. A. et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc. Natl. Acad. Sci. U. S. A. 104, 4401-4406, 2007.
  8. Crisan, M. et al. A reservoir of brown adipocyte progenitors in human skeletal muscle. Stem Cells 26, 2425-2433, 2008.
  9. Russell, A. P. et al. Brown adipocyte progenitor population is modified in obese and diabetic skeletal muscle. Int J Obes (Lond) 36, 155-158, 2012.
  10. Reinhart, B. J. et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901-906, 2000.
  11. Reinhart, B. J. et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis eleHamilton, A. J. & Baulcombe, D. C. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286, 950-952, 1999.ans. Nature 403, 901-906, 2000.
  12. Sun, L. et al. Mir193b-365 is essential for brown fat differentiation. Nat. Cell Biol. 13, 958-965, 2011.
  13. Yin, H. et al. MicroRNA-133 controls brown adipose determination in skeletal muscle satellite cells by targeting Prdm16. Cell metabolism 17, 210-224, 2013.