PMID- 36834930 OWN - NLM STAT- MEDLINE DCOM- 20230316 LR - 20230316 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 4 DP - 2023 Feb 9 TI - 7,8-Dihydroxyflavone Attenuates Inflammatory Response and Insulin Resistance Induced by the Paracrine Interaction between Adipocytes and Macrophages. LID - 10.3390/ijms24043520 [doi] LID - 3520 AB - Obesity-induced inflammation and insulin resistance are mediated by macrophage infiltration into adipose tissue. We investigated the effects of 7,8-dihydroxyflavone (7,8-DHF), a flavone found in plants, on the inflammatory response and insulin resistance induced by the interaction between adipocytes and macrophages. Hypertrophied 3T3-L1 adipocytes were cocultured with RAW 264.7 macrophages and treated with 7,8-DHF (3.12, 12.5, and 50 muM). The inflammatory cytokines and free fatty acid (FFA) release were evaluated by assay kits, and signaling pathways were determined by immunoblotting. Coculture of adipocytes and macrophages increased inflammatory mediators, such as nitric oxide (NO), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) and FFA secretion but suppressed the production of anti-inflammatory adiponectin. 7,8-DHF counteracted the coculture-induced changes (p < 0.001). 7,8-DHF also inhibited c-Jun N-terminal kinase (JNK) activation and blocked nuclear factor kappa B (NF-kappaB) nuclear translocation in the coculture system (p < 0.01). In addition, adipocytes cocultured with macrophages did not increase glucose uptake and Akt phosphorylation in response to insulin. However, 7,8-DHF treatment recovered the impaired responsiveness to insulin (p < 0.01). These findings show that 7,8-DHF alleviates inflammation and adipocyte dysfunction in the coculture of hypertrophied 3T3-L1 adipocytes and RAW 264.7 macrophages, indicating its potential as a therapeutic agent for obesity-induced insulin resistance. FAU - Shin, Ye-Eun AU - Shin YE AD - Department of Food Science & Nutrition, The Catholic University of Korea, Bucheon 14662, Republic of Korea. FAU - Choi, Ji Won AU - Choi JW AD - Department of Biotechnology, Graduate School, The Catholic University of Korea, Bucheon 14662, Republic of Korea. FAU - Park, Yong Il AU - Park YI AD - Department of Biotechnology, Graduate School, The Catholic University of Korea, Bucheon 14662, Republic of Korea. FAU - Kim, Hye-Kyeong AU - Kim HK AUID- ORCID: 0000-0003-1659-1709 AD - Department of Food Science & Nutrition, The Catholic University of Korea, Bucheon 14662, Republic of Korea. LA - eng GR - Research Fund,2022/The Catholic University of Korea/ PT - Journal Article DEP - 20230209 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (6,7-dihydroxyflavone) RN - 0 (Insulin) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Flavones) SB - IM MH - Animals MH - Mice MH - 3T3-L1 Cells MH - *Adipocytes/metabolism MH - Coculture Techniques MH - *Inflammation/metabolism MH - Insulin/metabolism MH - *Insulin Resistance MH - *Macrophages/metabolism MH - Obesity/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - *Flavones/metabolism/pharmacology MH - Paracrine Communication PMC - PMC9961847 OTO - NOTNLM OT - 7,8-dihydroxyflavone OT - adipocyte OT - inflammation OT - insulin resistance OT - macrophage COIS- The authors declare no conflict of interest. EDAT- 2023/02/26 06:00 MHDA- 2023/03/03 06:00 PMCR- 2023/02/09 CRDT- 2023/02/25 02:42 PHST- 2023/01/02 00:00 [received] PHST- 2023/02/07 00:00 [revised] PHST- 2023/02/08 00:00 [accepted] PHST- 2023/02/25 02:42 [entrez] PHST- 2023/02/26 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/09 00:00 [pmc-release] AID - ijms24043520 [pii] AID - ijms-24-03520 [pii] AID - 10.3390/ijms24043520 [doi] PST - epublish SO - Int J Mol Sci. 2023 Feb 9;24(4):3520. doi: 10.3390/ijms24043520.