Peter Arner1, Paul Petrus1, David Esteve2, Anne Boulomié2, Erik Näslund3, Anders Thorell4, Hui Gao1, Ingrid Dahlman1, Mikael Rydén5. 1. Department of Medicine (H7), Karolinska Institutet, 141 86, Stockholm, Sweden. 2. Inserm, UMR 1048, Team 1, I2MC, Institute of Metabolic and Cardiovascular Diseases, BP84225, 31432, Toulouse Cedex 4, France. 3. Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, 182 88, Stockholm, Sweden. 4. Division of Surgery, Ersta Hospital & Department of Clinical Science, Danderyd Hospital, Karolinska Institutet, 182 88, Stockholm, Sweden. 5. Department of Medicine (H7), Karolinska Institutet, 141 86, Stockholm, Sweden. mikael.ryden@ki.se.
Abstract
BACKGROUND: Adipokines are peptides secreted from white adipose tissue (WAT), which have been linked to WAT dysfunction and metabolic complications of obesity. We set out to identify novel adipokines in subcutaneous WAT (sWAT) linked to insulin resistance (IR). METHODS: Gene expression was determined by microarray and qPCR in obese and non-obese subjects with varying degree of IR. WAT-secreted and circulating protein levels were measured by ELISA. RESULTS: In sWAT of 80 obese women discordant for IR, 44 genes encoding potential adipose-secreted proteins were differentially expressed. Among these, merely two proteins, S100A4 and MXRA5 were released from sWAT in a time-dependent manner (criterion for true adipokines) but only the circulating levels of S100A4 were higher in IR. In two additional cohorts (n = 29 and n = 56), sWAT S100A4 secretion was positively and BMI-independently associated with IR (determined by clamp or HOMA-IR), ATP-III risk score and adipocyte size (hypertrophy). In non-obese (n = 20) and obese subjects before and after bariatric surgery (n = 21), circulating and sWAT-secreted levels were highest in the obese and normalized following weight loss. Serum S100A4 concentrations were higher in subjects with type 2 diabetes. S100A4 sWAT expression associated positively with genes involved in inflammation/extracellular matrix formation and inversely with genes in metabolic pathways. Although S100A4 was expressed in both stromal cells and adipocytes, only the expression in adipocytes associated with BMI. CONCLUSIONS: S100A4 is a novel adipokine associated with IR and sWAT inflammation/adipocyte hypertrophy independently of BMI. Its value as a circulating marker for dysfunctional WAT and IR needs to be validated in larger cohorts.
BACKGROUND: Adipokines are peptides secreted from white adipose tissue (WAT), which have been linked to WAT dysfunction and metabolic complications of obesity. We set out to identify novel adipokines in subcutaneous WAT (sWAT) linked to insulin resistance (IR). METHODS: Gene expression was determined by microarray and qPCR in obese and non-obese subjects with varying degree of IR. WAT-secreted and circulating protein levels were measured by ELISA. RESULTS: In sWAT of 80 obesewomen discordant for IR, 44 genes encoding potential adipose-secreted proteins were differentially expressed. Among these, merely two proteins, S100A4 and MXRA5 were released from sWAT in a time-dependent manner (criterion for true adipokines) but only the circulating levels of S100A4 were higher in IR. In two additional cohorts (n = 29 and n = 56), sWAT S100A4 secretion was positively and BMI-independently associated with IR (determined by clamp or HOMA-IR), ATP-III risk score and adipocyte size (hypertrophy). In non-obese (n = 20) and obese subjects before and after bariatric surgery (n = 21), circulating and sWAT-secreted levels were highest in the obese and normalized following weight loss. Serum S100A4 concentrations were higher in subjects with type 2 diabetes. S100A4 sWAT expression associated positively with genes involved in inflammation/extracellular matrix formation and inversely with genes in metabolic pathways. Although S100A4 was expressed in both stromal cells and adipocytes, only the expression in adipocytes associated with BMI. CONCLUSIONS:S100A4 is a novel adipokine associated with IR and sWAT inflammation/adipocyte hypertrophy independently of BMI. Its value as a circulating marker for dysfunctional WAT and IR needs to be validated in larger cohorts.
Authors: Evanna L Mills; Cathal Harmon; Mark P Jedrychowski; Haopeng Xiao; Anja V Gruszczyk; Gary A Bradshaw; Nhien Tran; Ryan Garrity; Dina Laznik-Bogoslavski; John Szpyt; Hannah Prendeville; Lydia Lynch; Michael P Murphy; Steven P Gygi; Bruce M Spiegelman; Edward T Chouchani Journal: Cell Metab Date: 2021-12-02 Impact factor: 31.373
Authors: Yin Hua Zhang; De Qiang Ma; De Ping Ding; Juan Li; Lin Li Chen; Kang Jian Ao; You You Tian Journal: Yonsei Med J Date: 2018-11 Impact factor: 2.759
Authors: Siri D Taxerås; María Galán; Laura Campderros; Irene Piquer-Garcia; Silvia Pellitero; Eva Martínez; Rocío Puig; Icíar Lucena; Jordi Tarascó; Pau Moreno; José Balibrea; Joan Bel; Marta Murillo; María Martínez; Marta Ramon-Krauel; Manel Puig-Domingo; Francesc Villarroya; Carles Lerin; David Sánchez-Infantes Journal: Obes Sci Pract Date: 2019-12-02