PMID- 24465779 OWN - NLM STAT- MEDLINE DCOM- 20141029 LR - 20220318 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 1 DP - 2014 TI - Effect of Sfrp5 on cytokine release and insulin action in primary human adipocytes and skeletal muscle cells. PG - e85906 LID - 10.1371/journal.pone.0085906 [doi] LID - e85906 AB - Secreted frizzled-related protein 5 (Sfrp5) is an adipokine with anti-inflammatory and insulin-sensitizing properties in mice. However, the mechanism of Sfrp5 action, especially in humans, is largely unknown. Therefore, cytokine release and insulin signaling were analyzed to investigate the impact of Sfrp5 on inflammation and insulin signaling in primary human adipocytes and skeletal muscle cells (hSkMC). Sfrp5 neither affected interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1) and adiponectin release from human adipocytes, nor IL-6 and IL-8 release from hSkMC. In tumor necrosis factor (TNF) alpha-treated adipocytes, Sfrp5 reduced IL-6 release by 49% (p<0.05), but did not affect MCP-1 and adiponectin release. In MCP-1-treated hSkMC, Sfrp5 did not affect cytokine secretion. In untreated adipocytes, Sfrp5 decreased the insulin-mediated phosphorylation of Akt-Ser473, Akt-Thr308, GSK3alpha-Ser21 and PRAS40-Thr246 by 34% (p<0.01), 31% (p<0.05), 37% (p<0.05) and 34% (p<0.01), respectively, and the stimulation of glucose uptake by 25% (p<0.05). Incubation with TNFalpha increased the phosphorylation of JNK and NFkappaB, and impaired insulin signaling. When Sfrp5 and TNFalpha were combined, there was no additional effect on insulin signaling and JNK phosphorylation, but phosphorylation of NFkappaB was reversed to basal levels. Sfrp5 had no effect on insulin signaling in untreated or in MCP-1 treated hSkMC. Thus, Sfrp5 lowered IL-6 release and NFkappaB phosphorylation in cytokine-treated human adipocytes, but not under normal conditions, and decreased insulin signaling in untreated human adipocytes. Sfrp5 did not act on hSkMC. Therefore, the cellular actions of Sfrp5 seem to depend on the type of tissue as well as its inflammatory and metabolic state. FAU - Carstensen, Maren AU - Carstensen M AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Dusseldorf, Germany ; German Center for Diabetes Research (DZD), Dusseldorf, Germany. FAU - Wiza, Claudia AU - Wiza C AD - German Center for Diabetes Research (DZD), Dusseldorf, Germany ; Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Dusseldorf, Germany. FAU - Rohrig, Karin AU - Rohrig K AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Dusseldorf, Germany ; German Center for Diabetes Research (DZD), Dusseldorf, Germany. FAU - Fahlbusch, Pia AU - Fahlbusch P AD - German Center for Diabetes Research (DZD), Dusseldorf, Germany ; Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Dusseldorf, Germany. FAU - Roden, Michael AU - Roden M AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Dusseldorf, Germany ; German Center for Diabetes Research (DZD), Dusseldorf, Germany ; Department of Endocrinology and Diabetology, University Hospital Dusseldorf, Dusseldorf, Germany. FAU - Herder, Christian AU - Herder C AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Dusseldorf, Germany ; German Center for Diabetes Research (DZD), Dusseldorf, Germany. FAU - Ouwens, D Margriet AU - Ouwens DM AD - German Center for Diabetes Research (DZD), Dusseldorf, Germany ; Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Dusseldorf, Dusseldorf, Germany ; Department of Endocrinology, Ghent University Hospital, Ghent, Belgium. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140121 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Cytokines) RN - 0 (Eye Proteins) RN - 0 (Insulin) RN - 0 (Membrane Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (SFRP5 protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (WNT5A protein, human) RN - 0 (Wnt Proteins) RN - 0 (Wnt-5a Protein) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Adipocytes/drug effects/*metabolism MH - Adolescent MH - Adult MH - Animals MH - Cells, Cultured MH - Cytokines/*metabolism MH - Eye Proteins/metabolism/*pharmacology MH - Female MH - Glucose/metabolism MH - Humans MH - Inflammation/metabolism/pathology MH - Insulin/*metabolism MH - Male MH - Membrane Proteins/metabolism/*pharmacology MH - Mice MH - Middle Aged MH - Muscle Cells/drug effects/*metabolism MH - Muscle, Skeletal/*cytology MH - Proto-Oncogene Proteins/metabolism MH - Signal Transduction/drug effects MH - Tumor Necrosis Factor-alpha/pharmacology MH - Wnt Proteins/metabolism MH - Wnt-5a Protein MH - Young Adult PMC - PMC3897555 COIS- Competing Interests: The authors have read the journal's policy and have the following conflicts: Christian Herder is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2014/01/28 06:00 MHDA- 2014/10/30 06:00 PMCR- 2014/01/21 CRDT- 2014/01/28 06:00 PHST- 2013/08/06 00:00 [received] PHST- 2013/12/09 00:00 [accepted] PHST- 2014/01/28 06:00 [entrez] PHST- 2014/01/28 06:00 [pubmed] PHST- 2014/10/30 06:00 [medline] PHST- 2014/01/21 00:00 [pmc-release] AID - PONE-D-13-32320 [pii] AID - 10.1371/journal.pone.0085906 [doi] PST - epublish SO - PLoS One. 2014 Jan 21;9(1):e85906. doi: 10.1371/journal.pone.0085906. eCollection 2014.