title: Inhibition of adipogenesis and induction of apoptosis and lipolysis by stem bromelain in 3T3-L1 adipocytes.
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/EBPα and PPARγ independent of C/EBPβ 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 PPARγ expression seems to stem from its ability to inhibit Akt and augment the TNFα pathway. The Akt-TSC2-mTORC1 pathway has recently been described for PPARγ expression in adipocytes. In our experiments, TNFα 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 G(i)α(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 PPARγ-regulated adipogenesis pathway at all stages and by augmenting TNFα-induced lipolysis and apoptosis in mature adipocytes.
authors.affiliation: Institute of Microbial Technology (CSIR), Chandigarh, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dave
authors.forename: Naval Jit
authors.initials: NJ
authors.lastname: Kaur
authors.forename: Ravikanth
authors.initials: R
authors.lastname: Nanduri
authors.forename: H Kitdorlang
authors.initials: HK
authors.lastname: Dkhar
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.forename: Pawan
authors.initials: P
authors.lastname: Gupta
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D001963:Bromelains / Q000494:pharmacology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C545013:Cebpb protein, mouse; C497253:Cebpd protein, mouse; D000960:Hypolipidemic Agents; D047495:PPAR gamma; D051743:CCAAT-Enhancer-Binding Protein-delta; D001963:Bromelains; C091760:stem bromelain