Fig. 12

Hypothetical pathways based on the results of the present study and our previous data. a The effect of butyrate on PGE2 production in the interaction between co-cultured macrophages and adipocytes. Co-culture elevates cPLA2 activity in macrophages, sPLA2 activity in adipocytes and macrophages, and the expression of AdPLA2 protein and mRNA in adipocytes. Butyrate elevates cPLA2 activity to a greater degree in macrophages. Co-culture elevates COX2 expression in both cells, and butyrate further enhances COX2 expression in both cells. Thus, butyrate increases PGE2 production more than co-culture alone. b The effects of butyrate and PGE2 on lipolysis in co-cultured adipocytes. Co-culture increases cAMP and PKA (PRKAR1A) levels in adipocytes and increases the release of FFAs and free glycerol into the medium (lipolysis). Butyrate suppresses cAMP and PKA levels, and exogenous PGE2 has a lesser effect than butyrate. These suppressive effects may reduce the activities of lipases, including ATGL and HSL, thus resulting in inhibition of lipolysis. c The effects of butyrate and exogenous PGE2 on cAMP- and NF-κB–mediated lipolysis in TNF-α–stimulated 3T3-L1 adipocytes. Co-culture increases TNF-α production. TNF-α increases cAMP, leading to increased lipolysis. Anti–TNF-α antibody, butyrate, or exogenous PGE2 decrease cAMP levels and reduce lipolysis in TNF-α–stimulated 3T3-L1 cells. The GPR109A-mediated pathway may be the predominant pathway regulating the effect of butyrate on lipolysis in TNF-α–stimulated 3T3-L1 cells