@article{vonLoeffelholzLieskeNeuschaeferRubeetal.2017, author = {von Loeffelholz, Christian and Lieske, Stefanie and Neuschaefer-Rube, Frank and Willmes, Diana M. and Raschzok, Nathanael and Sauer, Igor M. and K{\"o}nig, J{\"o}rg and Fromm, Martin F. and Horn, Paul and Chatzigeorgiou, Antonios and Pathe-Neuschaefer-Rube, Andrea and Jordan, Jens and Pfeiffer, Andreas F. H. and Mingrone, Geltrude and Bornstein, Stefan R. and Stroehle, Peter and Harms, Christoph and Wunderlich, F. Thomas and Helfand, Stephen L. and Bernier, Michel and de Cabo, Rafael and Shulman, Gerald I. and Chavakis, Triantafyllos and P{\"u}schel, Gerhard Paul and Birkenfeld, Andreas L.}, title = {The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism}, series = {Hepatology}, volume = {66}, journal = {Hepatology}, number = {2}, publisher = {Wiley}, address = {Hoboken}, issn = {0270-9139}, doi = {10.1002/hep.29089}, pages = {616 -- 630}, year = {2017}, abstract = {Reduced expression of the Indy ("I am Not Dead, Yet") gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane-associated citrate transporter expressed highly in the liver, protects mice from high-fat diet-induced and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We studied a possible role of mIndy in human hepatic fat metabolism. In obese, insulin-resistant patients with nonalcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In nonhuman primates, a 2-year high-fat, high-sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription through the IL-6 receptor and activation of the transcription factor signal transducer and activator of transcription 3, and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-signal transducer and activator of transcription 3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx, and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and nonhuman primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 through mINDY. Conclusion: Targeting human mINDY may have therapeutic potential in obese patients with nonalcoholic fatty liver disease. German Clinical Trials Register: DRKS00005450.}, language = {en} } @article{WendtHufenbachKoenigetal.2020, author = {Wendt, Julia and Hufenbach, Miriam Catrin and K{\"o}nig, J{\"o}rg and Hamm, Alfons O.}, title = {Effects of verbal instructions and physical threat removal prior to extinction training on the return of conditioned fear}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, publisher = {Macmillan Publishers Limited, part of Springer Nature}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-020-57934-7}, pages = {14}, year = {2020}, abstract = {Instructions given prior to extinction training facilitate the extinction of conditioned skin conductance (SCRs) and fear-potentiated startle responses (FPSs) and serve as laboratory models for cognitive interventions implemented in exposure-based treatments of pathological anxiety. Here, we investigated how instructions given prior to extinction training, with or without the additional removal of the electrode used to deliver the unconditioned stimulus (US), affect the return of fear assessed 24 hours later. We replicated previous instruction effects on extinction and added that the additional removal of the US electrode slightly enhanced facilitating effects on the extinction of conditioned FPSs. In contrast, extinction instructions hardly affected the return of conditioned fear responses. These findings suggest that instruction effects observed during extinction training do not extent to tests of return of fear 24 hours later which serve as laboratory models of relapse and improvement stability of exposure-based treatments.}, language = {en} } @misc{WendtHufenbachKoenigetal.2020, author = {Wendt, Julia and Hufenbach, Miriam Catrin and K{\"o}nig, J{\"o}rg and Hamm, Alfons O.}, title = {Effects of verbal instructions and physical threat removal prior to extinction training on the return of conditioned fear}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {599}, issn = {1866-8364}, doi = {10.25932/publishup-44479}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-444796}, pages = {16}, year = {2020}, abstract = {Instructions given prior to extinction training facilitate the extinction of conditioned skin conductance (SCRs) and fear-potentiated startle responses (FPSs) and serve as laboratory models for cognitive interventions implemented in exposure-based treatments of pathological anxiety. Here, we investigated how instructions given prior to extinction training, with or without the additional removal of the electrode used to deliver the unconditioned stimulus (US), affect the return of fear assessed 24 hours later. We replicated previous instruction effects on extinction and added that the additional removal of the US electrode slightly enhanced facilitating effects on the extinction of conditioned FPSs. In contrast, extinction instructions hardly affected the return of conditioned fear responses. These findings suggest that instruction effects observed during extinction training do not extent to tests of return of fear 24 hours later which serve as laboratory models of relapse and improvement stability of exposure-based treatments.}, language = {en} }