TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin

A. Goralczyk, M. van Vijven, M. Koch, C. Badowski, M.S. Yassin, S.A. Toh, A. Shabbir, A. Franco-Obregón, M. Raghunath

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Abstract

Transient receptor potential (TRP) channels are polymodal cell sensors responding to diverse stimuli and widely implicated in the developmental programs of numerous tissues. The evidence for an involvement of TRP family members in adipogenesis, however, is scant. We present the first comprehensive expression profile of all known 27 human TRP genes in mesenchymal progenitors cells during white or brown adipogenesis. Using positive trilineage differentiation as an exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to be uniquely adipospecific. Knockdown of TRPP3 repressed the expression of the brown fat signature genes uncoupling protein (UCP)-1 and peroxisome proliferator-activated receptor γ coactivator (PGC)-1α as well as attenuated forskolin-stimulated uncoupled respiration. However, indices of generalized adipogenesis, such as lipid droplet morphology and fatty acid binding protein (FAPB)-4 expression, were not affected, indicating a principal mitochondrial role of TRPP3. Conversely, activating TRPM8 with menthol up-regulated UCP-1 expression and augmented uncoupled respiration predominantly in white adipocytes (browning), whereas streptomycin antagonized TRPM8-mediated calcium entry, downregulated UCP-1 expression, and mitigated uncoupled respiration; menthol was less capable of augmenting uncoupled respiration (thermogenesis) in brown adipocytes. TRPP3 and TRPM8 hence appear to be involved in the priming of mitochondria to perform uncoupled respiration downstream of adenylate cyclase. Our results also underscore the developmental caveats of using antibiotics in adipogenic studies.-Goralczyk, A., van Vijven, M., Koch, M., Badowski, C., Yassin, M. S., Toh, S.-A., Shabbir, A., Franco-Obregón, A., Raghunath, M. TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin.

Original languageEnglish
Pages (from-to)3251-3266
Number of pages16
JournalThe FASEB Journal
Volume31
Issue number8
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

  • Adipogenesis
  • Aminoglycoside antibiotics
  • Browning
  • TRPM8
  • TRPP3
  • Humans
  • Membrane Proteins/genetics
  • Adipose Tissue, White/metabolism
  • Transient Receptor Potential Channels/genetics
  • Mesenchymal Stem Cells/cytology
  • Streptomycin/adverse effects
  • Young Adult
  • Calcium Channels/genetics
  • Receptors, Cell Surface/genetics
  • Protein Isoforms
  • Adipose Tissue, Brown/metabolism
  • Adult
  • Adipogenesis/physiology
  • Cell Differentiation
  • Gene Expression Regulation/physiology
  • Anti-Bacterial Agents/adverse effects

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