GDF10 is related to obesity as an adipokine derived from subcutaneous adipose tissue

Introduction Adipokines are proteins that are secreted by the adipose tissue. Although they are associated with obesity-related metabolic disorders, most studies have focused on adipokines expressed by visceral adipose tissue (VAT). This study aimed to identify the adipokine potentially derived from subcutaneous adipose tissue (SAT) and its clinical significance. Methods Samples of SAT and VAT were obtained from six adult male patients who underwent laparoscopic surgery for benign gall bladder disease. Differentially expressed genes were analyzed by subjecting the samples to RNA sequencing. The serum concentration of selected proteins according to body mass index (BMI) was analyzed in 58 individuals. Results GDF10 showed significantly higher expression in the SAT, as per RNA sequencing (fold change = 5.8, adjusted P value = 0.009). Genes related to insulin response, glucose homeostasis, lipid homeostasis, and fatty acid metabolism were suppressed when GDF10 expression was high in SAT, as per genotype-tissue expression data. The serum GDF10 concentration was higher in participants with BMI ≥ 25 kg/m2 (n = 35, 2674 ± 441 pg/mL) than in those with BMI < 25 kg/m2 (n = 23, 2339 ± 639 pg/mL; P = 0.022). There was a positive correlation between BMI and serum GDF10 concentration (r = 0.308, P = 0.019). Conclusions GDF10 expression was higher in SAT than in VAT. Serum GDF10 concentration was high in patients with obesity. Therefore, GDF10 could be a SAT-derived protein related to obesity.

[1]  A. Stancic,et al.  Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles , 2021, Archives of medical science : AMS.

[2]  J. Ralston,et al.  Economic impacts of overweight and obesity: current and future estimates for eight countries , 2021, BMJ Global Health.

[3]  J. A. Suárez-Cuenca,et al.  Enlarged adipocytes from subcutaneous vs. visceral adipose tissue differentially contribute to metabolic dysfunction and atherogenic risk of patients with obesity , 2021, Scientific Reports.

[4]  M. Stumvoll,et al.  Identification of distinct transcriptome signatures of human adipose tissue from fifteen depots , 2020, European Journal of Human Genetics.

[5]  C. Kahn,et al.  Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. , 2019, The Journal of clinical investigation.

[6]  J. Krepinsky,et al.  GDF10 blocks hepatic PPARγ activation to protect against diet-induced liver injury , 2019, Molecular metabolism.

[7]  Huiguang Wu,et al.  Integrative Analysis Revealing Human Adipose-Specific Genes and Consolidating Obesity Loci , 2019, Scientific Reports.

[8]  K. Tsuchida,et al.  Overexpression of bone morphogenetic protein-3b (BMP-3b) in adipose tissues protects against high-fat diet-induced obesity , 2017, International Journal of Obesity.

[9]  R. Pišot,et al.  Gene expression regional differences in human subcutaneous adipose tissue , 2017, BMC Genomics.

[10]  Jeffrey T Leek,et al.  Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown , 2016, Nature Protocols.

[11]  Steven L Salzberg,et al.  HISAT: a fast spliced aligner with low memory requirements , 2015, Nature Methods.

[12]  S. Salzberg,et al.  StringTie enables improved reconstruction of a transcriptome from RNA-seq reads , 2015, Nature Biotechnology.

[13]  Jingyuan Fu,et al.  Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity , 2015, Nutrition & Diabetes.

[14]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[15]  N. Pivac,et al.  Gene expression in visceral and subcutaneous adipose tissue in overweight women. , 2012, Frontiers in bioscience.

[16]  T. McLaughlin,et al.  Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. , 2011, The Journal of clinical endocrinology and metabolism.

[17]  K. Kangawa,et al.  Bone morphogenetic protein-3b (BMP-3b) is expressed in adipocytes and inhibits adipogenesis as a unique complex , 2011, International Journal of Obesity.

[18]  P. Scherer,et al.  Adipokines as novel biomarkers and regulators of the metabolic syndrome , 2010, Annals of the New York Academy of Sciences.

[19]  D. Chisholm,et al.  Subcutaneous and Visceral Adipose Tissue Gene Expression of Serum Adipokines That Predict Type 2 Diabetes , 2010, Obesity.

[20]  M. Ibrahim.  Subcutaneous and visceral adipose tissue: structural and functional differences , 2010, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[21]  Udo Hoffmann,et al.  Abdominal Visceral and Subcutaneous Adipose Tissue Compartments: Association With Metabolic Risk Factors in the Framingham Heart Study , 2007, Circulation.

[22]  Philipp E. Scherer,et al.  Visceral Fat Adipokine Secretion Is Associated With Systemic Inflammation in Obese Humans , 2007, Diabetes.

[23]  R. A. Forse,et al.  Fat Depot–Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes , 2006, Diabetes.

[24]  C. Kahn,et al.  Evidence for a role of developmental genes in the origin of obesity and body fat distribution. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[25]  C. Newgard,et al.  Metabolism: A is for adipokine , 2005, Nature.

[26]  T. Hudson,et al.  A survey of genes differentially expressed in subcutaneous and visceral adipose tissue in men. , 2004, Obesity research.

[27]  A. Madan,et al.  Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. , 2004, Endocrinology.

[28]  K. Kangawa,et al.  Bone morphogenetic protein-3 family members and their biological functions. , 2004, Frontiers in bioscience : a journal and virtual library.

[29]  A. Lawler,et al.  Characterization of GDF-10 expression patterns and null mice. , 1999, Developmental biology.

[30]  M. Gerstein,et al.  RNA-Seq: a revolutionary tool for transcriptomics , 2009, Nature Reviews Genetics.

[31]  N. Copeland,et al.  Growth/differentiation factor-10: a new member of the transforming growth factor-beta superfamily related to bone morphogenetic protein-3. , 1995, Growth factors.