Harper 2012 Abstract Bioblast

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Harper ME, Yin H, Pasut A, Soleimani VD, Bentzinger CF, Antoun G, Thorn S, Seale P, Fernando P, Van IJcken W Frank Grosveld F, Dekemp RA, Boushel RC, Rudnicki MA (2012) Metabolic effects of microRNA-133 and its antagomir in mice. Mitochondr Physiol Network 17.12.

Link: MiPNet17.12 Bioblast 2012 - Open Access

Harper ME, Yin H, Pasut A, Soleimani VD, Bentzinger CF, Antoun G, Thorn S, Seale P, Fernando P, Van IJcken W Frank Grosveld F, Dekemp RA, Boushel RC, Rudnicki MA (2012)

Event: Bioblast 2012

Mary-Elle Harper

The unequivocal identification of functional brown adipose tissue (BAT) in adult humans (reviewed in [1]) has led to a resurgence of interest in this unique tissue and its potential in novel anti-obesity therapies [2,3]. Unlike white adipose tissue, BAT is rich with mitochondria. BAT is capable of remarkably high rates of uncoupled respiration due to the activity of uncoupling protein-1 (UCP-1). The cellular origins of brown adipocytes are not well understood, but the transcription factor Prdm16 is necessary and sufficient in establishing brown adipocyte lineage [4]. In vitro loss-of-function of Prdm16 induces myogenic differentiation of committed preadipocytes from BAT, while gain-of-function induces committed myoblasts to differentiate into brown adipocytes [4]. Satellite cells are adult skeletal muscle stem cells, located beneath the basal lamina of muscle, and when activated, they proliferate and differentiate into multi-nucleated muscle cells. In this study we show that brown adipocyte determination of satellite cells is controlled by miR-133. Loss-of-function of miR-133 during muscle regeneration in mice commits satellite cells to the brown adipocyte lineage, causing local uncoupled respiration, increased glucose uptake and whole body thermogenesis, as well as decreased diet–induced obesity.

  1. Celi FS (2009) Brown adipose tissue--when it pays to be inefficient. N Engl J Med 360: 1553-1556. Open Access
  2. Himms-Hagen J (1984) Thermogenesis in brown adipose tissue as an energy buffer. Implications for obesity. N Engl J Med 311: 1549-1558.
  3. Cypess AM, Kahn CR (2010) Brown fat as a therapy for obesity and diabetes. Curr Opin Endocrinol Diabetes Obes 17: 143-149.

Keywords: Uncoupling protein-1 (UCP1), Brown fat, Thermogenesis, Obesity

O2k-Network Lab: CA Ottawa Harper ME, DK Copenhagen Dela F, CA Vancouver Boushel RC


Organism: Mouse  Tissue;cell: Skeletal muscle, Fat  Preparation: Intact organism, Permeabilized cells 

Coupling state: LEAK 

HRR: Oxygraph-2k 

Affiliations and author contributions

Mary-Ellen Harper (1), Hang Yin, Alessandra Pasut, Vahab D Soleimani, C Florian Bentzinger, Ghadi Antoun, Stephanie Thorn, Patrick Seale, Pasan Fernando, Wilfred van IJcken, Frank Grosveld, Robert A Dekemp, Robert Boushel, Michael A Rudnicki

(1) Mitochondrial Bioenergetics Laboratory, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada; Email: mharper@uottawa.ca

Supplementary references

4. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scimè A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454: 961-796. Open Access


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