@article{open1129,
          volume = {7},
          number = {1},
          author = {Massimo Federici and Sandeep Dave and Naval Jit Kaur and Ravikanth Nanduri and H Kitdorlang Dkhar and Ashwani Kumar and Pawan Gupta},
            note = {OPEN ACCESS},
           title = {Inhibition of Adipogenesis and Induction of Apoptosis and Lipolysis by Stem Bromelain in 3T3-L1 Adipocytes},
       publisher = {Public Library of Science (PLoS)},
            year = {2012},
         journal = {PLoS ONE},
           pages = {e30831},
             url = {http://crdd.osdd.net/open/1129/},
        abstract = {The phytotherapeutic protein stem bromelain (SBM) is used as an anti-obesity alternative medicine. We show at the cellular level that SBM irreversibly inhibits 3T3-L1 adipocyte differentiation by reducing adipogenic gene expression and induces apoptosis and lipolysis in mature adipocytes. At the molecular level, SBM suppressed adipogenesis by downregulating C/EBP{\ensuremath{\alpha}} and PPAR{\ensuremath{\gamma}} independent of C/EBP{\ensuremath{\beta}} gene expression. Moreover, mRNA levels of adipocyte fatty acid-binding protein (ap2), fatty acid synthase (FAS), lipoprotein lipase (LPL), CD36, and acetyl-CoA carboxylase (ACC) were also downregulated by SBM. Additionally, SBM reduced adiponectin expression and secretion. SBM's ability to repress PPAR{\ensuremath{\gamma}} expression seems to stem from its ability to inhibit Akt and augment the TNF{\ensuremath{\alpha}} pathway. The Akt?TSC2?mTORC1 pathway has recently been described for PPAR{\ensuremath{\gamma}} expression in adipocytes. In our experiments, TNF{\ensuremath{\alpha}} upregulation compromised cell viability of mature adipocytes (via apoptosis) and induced lipolysis. Lipolytic response was evident by downregulation of anti-lipolytic genes perilipin, phosphodiestersae-3B (PDE3B), and GTP binding protein Gi{\ensuremath{\alpha}}1, as well as sustained expression of hormone sensitive lipase (HSL). These data indicate that SBM, together with all-trans retinoic-acid (atRA), may be a potent modulator of obesity by repressing the PPAR{\ensuremath{\gamma}}-regulated adipogenesis pathway at all stages and by augmenting TNF{\ensuremath{\alpha}}-induced lipolysis and apoptosis in mature adipocytes}
}