Vittoria D'Esposito1,2, Maria Rosaria Ambrosio1,2, Domenico Liguoro1,2, Giuseppe Perruolo1,2, Manuela Lecce1,2, Serena Cabaro1,2, Marianna Aprile3, Ada Marino2, Vincenzo Pilone4, Pietro Forestieri4,5, Claudia Miele1,2, Dario Bruzzese6, Daniela Terracciano1,2, Francesco Beguinot1,2, Pietro Formisano7,8. 1. URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy. 2. Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy. 3. Institute of Genetics and Biophysics "Adriano Buzzati-Traverso," CNR, Naples, Italy. 4. Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy. 5. Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy. 6. Department of Public Health, "Federico II" University of Naples, Naples, Italy. 7. URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy. fpietro@unina.it. 8. Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy. fpietro@unina.it.
Abstract
BACKGROUND: Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. METHODS: Ninty-two severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an oral glucose tolerance test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and mesenchymal stem cells (MSCs) were isolated, characterized, and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines, and growth factors were assessed by multiplex ELISA. RESULTS: Serum levels of IL-9, IL-13, and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were threefold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT-derived MSCs to the anti-inflammatory flavonoid quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. CONCLUSION: In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and maybe, at least in part, attenuated by quercetin.
BACKGROUND: Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. METHODS: Ninty-two severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an oral glucose tolerance test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and mesenchymal stem cells (MSCs) were isolated, characterized, and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines, and growth factors were assessed by multiplex ELISA. RESULTS: Serum levels of IL-9, IL-13, and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were threefold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT-derived MSCs to the anti-inflammatory flavonoid quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. CONCLUSION: In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and maybe, at least in part, attenuated by quercetin.
Authors: Alessandro Gialluisi; Federica Santonastaso; Marialaura Bonaccio; Francesca Bracone; Nitin Shivappa; James R Hebert; Chiara Cerletti; Maria Benedetta Donati; Giovanni de Gaetano; Licia Iacoviello Journal: J Inflamm Res Date: 2021-09-28
Authors: Vittoria D'Esposito; Michele Francesco Di Tolla; Manuela Lecce; Francesco Cavalli; Michele Libutti; Saverio Misso; Serena Cabaro; Maria Rosaria Ambrosio; Alessia Parascandolo; Bianca Covelli; Giuseppe Perruolo; Mario Sansone; Pietro Formisano Journal: Front Nutr Date: 2022-06-24