Journal
FASEB JOURNAL
Volume 31, Issue 8, Pages 3251-3266Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201601081RR
Keywords
TRPM8; TRPP3; browning; adipogenesis; aminoglycoside antibiotics
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Funding
- NUS Tissue Engineering Programme (NUSTEP)
- NUS Faculty Research Committee [R-397-000-081-112]
- NUS Life Sciences Institute (MetaTEC) [R711-000-032101]
- Lee Foundation
- National Medical Research Council [NMRC/CSA034/2012]
- Singapore International Graduate Award
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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 gamma coactivator (PGC)-1 alpha 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.
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