PMID- 31547433 OWN - NLM STAT- MEDLINE DCOM- 20200210 LR - 20210226 IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 10 IP - 9 DP - 2019 Sep 12 TI - Transcriptional Analysis of FOXO1, C/EBP-alpha and PPAR-gamma2 Genes and Their Association with Obesity-Related Insulin Resistance. LID - 10.3390/genes10090706 [doi] LID - 706 AB - BACKGROUND: Obesity is associated with several comorbid disorders, ranging from cardiovascular diseases to insulin resistance. In this context, visceral adipose tissue (VAT) seems to have a close connection with insulin resistance. In our study, we hypothesized that the expression profile of key adipogenic genes, such as proliferator-activated receptor gamma type 2 (PPAR-gamma2), CCAAT/enhancer-binding protein type alpha (C/EBP-alpha), and forkhead box protein class O type 1 (FOXO1) in VAT should shed light on their association with obesity-related insulin resistance. METHODS: To test this idea, we studied the expression profile of C/EBP-alpha, FOXO1 and PPAR-gamma2 in VAT from non-obese individuals, and low insulin (LIR-MO) and high insulin morbidly obese (HIR-MO) subjects, through a combination of RT-qPCR, co-immunoprecipitation, ELISA, Western blot analysis and EMSA assays. RESULTS: Our results show that C/EBP-alpha and PPAR-gamma2 were down-expressed in HIR-MO individuals, while FOXO1 was overexpressed. In addition, the PPAR-gamma2-RXR-alpha heterodimer showed weak activity and bound weakly to the putative IGFBP-2-PPRE promoter sequence in VAT from HIR-MO subjects when compared with LIR-MO individuals. CONCLUSIONS: These results show that PPAR-gamma2, C/EBP-alpha, FOXO1 and IGFBP-2 have a close relationship with insulin resistance in VAT of morbidly obese individuals. FAU - Boughanem, Hatim AU - Boughanem H AUID- ORCID: 0000-0001-7743-311X AD - Biomedical Research Institute of Malaga (IBIMA), Faculty of Science, University of Malaga, 29010 Malaga, Spain. h.b.boughanem@gmail.com. FAU - Cabrera-Mulero, Amanda AU - Cabrera-Mulero A AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, Spain. amanda.c.mulero@hotmail.com. AD - CIBEROBN (CIBER in Physiopathology of Obesity and Nutrition CB06/03/0018), "Instituto de Salud Carlos III", 28029 Madrid, Spain. amanda.c.mulero@hotmail.com. FAU - Millan-Gomez, Mercedes AU - Millan-Gomez M AD - CIBERCV (CIBER in cardiovascular diseases), "Instituto de Salud Carlos III", 28029 Madrid, Spain. mercedesmillang@gmail.com. AD - Unidad de Gestion Clinica Area del Corazon, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, Spain. mercedesmillang@gmail.com. FAU - Garrido-Sanchez, Lourdes AU - Garrido-Sanchez L AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, Spain. lourgarrido@gmail.com. AD - CIBEROBN (CIBER in Physiopathology of Obesity and Nutrition CB06/03/0018), "Instituto de Salud Carlos III", 28029 Madrid, Spain. lourgarrido@gmail.com. FAU - Cardona, Fernando AU - Cardona F AUID- ORCID: 0000-0003-4460-6824 AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, Spain. fernandocardonadiaz@gmail.com. AD - CIBEROBN (CIBER in Physiopathology of Obesity and Nutrition CB06/03/0018), "Instituto de Salud Carlos III", 28029 Madrid, Spain. fernandocardonadiaz@gmail.com. FAU - Tinahones, Francisco Jose AU - Tinahones FJ AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, Spain. fjtinahones@hotmail.com. AD - CIBEROBN (CIBER in Physiopathology of Obesity and Nutrition CB06/03/0018), "Instituto de Salud Carlos III", 28029 Madrid, Spain. fjtinahones@hotmail.com. FAU - Moreno-Santos, Inmaculada AU - Moreno-Santos I AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, Spain. morenosantos.inma@gmail.com. FAU - Macias-Gonzalez, Manuel AU - Macias-Gonzalez M AUID- ORCID: 0000-0002-6475-4704 AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), 29010 Malaga, Spain. mmacias.manuel@gmail.com. AD - CIBEROBN (CIBER in Physiopathology of Obesity and Nutrition CB06/03/0018), "Instituto de Salud Carlos III", 28029 Madrid, Spain. mmacias.manuel@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190912 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 RN - 0 (CCAAT-Enhancer-Binding Protein-alpha) RN - 0 (FOXO1 protein, human) RN - 0 (Forkhead Box Protein O1) RN - 0 (IGFBP2 protein, human) RN - 0 (Insulin-Like Growth Factor Binding Protein 2) RN - 0 (PPAR gamma) RN - 0 (RNA, Messenger) SB - IM MH - Adult MH - Aged MH - CCAAT-Enhancer-Binding Protein-alpha/*genetics/metabolism MH - Female MH - Forkhead Box Protein O1/*genetics/metabolism MH - Humans MH - *Insulin Resistance MH - Insulin-Like Growth Factor Binding Protein 2/genetics/metabolism MH - Male MH - Middle Aged MH - Obesity, Morbid/*genetics/metabolism MH - PPAR gamma/*genetics/metabolism MH - RNA, Messenger/genetics/metabolism PMC - PMC6770962 OTO - NOTNLM OT - C/EBP-alpha OT - FOXO1 OT - IGFBP-2 OT - PPAR-gamma2 OT - insulin resistance OT - obesity COIS- The authors declared no conflict of interest. EDAT- 2019/09/25 06:00 MHDA- 2020/02/11 06:00 PMCR- 2019/09/01 CRDT- 2019/09/25 06:00 PHST- 2019/07/26 00:00 [received] PHST- 2019/08/28 00:00 [revised] PHST- 2019/09/10 00:00 [accepted] PHST- 2019/09/25 06:00 [entrez] PHST- 2019/09/25 06:00 [pubmed] PHST- 2020/02/11 06:00 [medline] PHST- 2019/09/01 00:00 [pmc-release] AID - genes10090706 [pii] AID - genes-10-00706 [pii] AID - 10.3390/genes10090706 [doi] PST - epublish SO - Genes (Basel). 2019 Sep 12;10(9):706. doi: 10.3390/genes10090706.