OBJECTIVE: Central obesity and sub-clinical inflammation increase metabolic risk, this study examined the intracellular inflammatory pathways in adipose tissue (AT) that contribute to this risk. DESIGN AND METHODS: This study therefore addressed the influence of NFκB and JNK activation in human abdominal subcutaneous (AbdSc) and omental (Om) AT, the effect of adiposity, T2DM status and the role of TNFα in vitro, using molecular biology techniques. RESULTS: Our data showed NFκB activity is increased in Om AT versus AbdSc AT (P<0.01), which was reversed with respect to depot specific activation of JNK (P<0.01). However, T2DM status appeared to preferentially activate NFκB (P<0.001) over JNK. Furthermore, in vitro studies showed recombinant human (rh) TNFα treated AbdSc adipocytes increased NFκB activity over time (2-48 h, P<0.05) whilst JNK activity reduced (2 h, 4 h, P<0.05); inhibitor studies supported a preferential role for NFκB as a modulator of TNFα secretion. CONCLUSIONS: These studies suggest distinct changes in NFκB and JNK activation, dependent upon AT depot, adiposity and T2DM status, with in vitro use of rh TNFα leading to activation of NFκB. Consequently NFκB appears to play a central role in inflammatory mediated metabolic disease over JNK, highlighting NFκB as a potential key target for therapeutic intervention.
OBJECTIVE: Central obesity and sub-clinical inflammation increase metabolic risk, this study examined the intracellular inflammatory pathways in adipose tissue (AT) that contribute to this risk. DESIGN AND METHODS: This study therefore addressed the influence of NFκB and JNK activation in human abdominal subcutaneous (AbdSc) and omental (Om) AT, the effect of adiposity, T2DM status and the role of TNFα in vitro, using molecular biology techniques. RESULTS: Our data showed NFκB activity is increased in Om AT versus AbdSc AT (P<0.01), which was reversed with respect to depot specific activation of JNK (P<0.01). However, T2DM status appeared to preferentially activate NFκB (P<0.001) over JNK. Furthermore, in vitro studies showed recombinant human (rh) TNFα treated AbdSc adipocytes increased NFκB activity over time (2-48 h, P<0.05) whilst JNK activity reduced (2 h, 4 h, P<0.05); inhibitor studies supported a preferential role for NFκB as a modulator of TNFα secretion. CONCLUSIONS: These studies suggest distinct changes in NFκB and JNK activation, dependent upon AT depot, adiposity and T2DM status, with in vitro use of rh TNFα leading to activation of NFκB. Consequently NFκB appears to play a central role in inflammatory mediated metabolic disease over JNK, highlighting NFκB as a potential key target for therapeutic intervention.
Authors: Mark P Jedrychowski; Libin Liu; Collette J Laflamme; Kalypso Karastergiou; Tova Meshulam; Shi-Ying Ding; Yuanyuan Wu; Mi-Jeong Lee; Steven P Gygi; Susan K Fried; Paul F Pilch Journal: Mol Metab Date: 2015-09-18 Impact factor: 7.422
Authors: Ping Rao; Yong Zhou; Si-Qi Ge; An-Xin Wang; Xin-Wei Yu; Mohamed Ali Alzain; Andrea Katherine Veronica; Jing Qiu; Man-Shu Song; Jie Zhang; Hao Wang; Hong-Hong Fang; Qing Gao; You-Xin Wang; Wei Wang Journal: Int J Environ Res Public Health Date: 2016-08-30 Impact factor: 3.390
Authors: Danyelle M Liddle; Amber L Hutchinson; Hannah R Wellings; Krista A Power; Lindsay E Robinson; Jennifer M Monk Journal: Nutrients Date: 2017-11-27 Impact factor: 5.717