Abnormal expression of genes involved in inflammation, lipid metabolism, and Wnt signaling in the adipose tissue of polycystic ovary syndrome

Gregorio Chazenbalk, Yen Hao Chen, Saleh Heneidi, Jung Min Lee, Marita Pall, Yii Der Ida Chen, Ricardo Azziz

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Context: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. Objective: Our objective was to compare gene expression pattern in sc abdominal adipose tissue in nonobese PCOS patients vs. body mass index-matched controls. Research Design and Methods: Eleven PCOS subjects and 12 controls (body mass index 20-28 kg/m2) were recruited. Total RNA was isolated, and gene expression profiling was performed using Affymetrix Human Genome U133 arrays. Differentially expressed genes were classified by gene ontology. Microarray results for selected genes were confirmed by quantitative real-time PCR (RT-qPCR). Frequently sampled iv glucose tolerance tests were used to assess dynamic insulin sensitivity. Results: Ninety-six genes were identified with altered expression of at least 2-fold in nonobese PCOS adipose tissues. Inflammatory response genes were significantly down-regulated. RT-qPCR confirmed decreases in expression of IL6 (12.3-fold), CXCL2(18.3-fold), and SOCS3(22.6-fold). Lipid metabolism genes associated with insulin resistance were significantly up-regulated, with confirmed increases in DHRS9 (2.5-fold), UCLH1 (2.6-fold), and FADS1 (2.8-fold) expression. Wnt signaling genes (DKK2, JUN, and FOSB) were differentially expressed. RT-qPCR confirmed significant expression changes in DKK2 (1.9-fold increase), JUN (4.1-fold decrease), and FOSB (60-fold decrease). Conclusions: Genes involved in inflammation, lipid metabolism, and Wnt signaling are differentially expressed in nonobese PCOS adipose tissue. Because these genes are known to affect adipogenesis and insulin resistance, we hypothesize that their dysregulation may contribute to the metabolic abnormalities observed in women with PCOS.

Original languageEnglish (US)
Pages (from-to)E765-E770
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number5
DOIs
StatePublished - May 1 2012

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Polycystic Ovary Syndrome
Lipid Metabolism
Adipose Tissue
Genes
Tissue
Inflammation
Gene Expression
Insulin Resistance
Insulin
Body Mass Index
Gene expression
Adipogenesis
Abdominal Fat
Gene Ontology
Gene Expression Profiling
Human Genome
Glucose Tolerance Test
Real-Time Polymerase Chain Reaction
Interleukin-6
Microarrays

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Abnormal expression of genes involved in inflammation, lipid metabolism, and Wnt signaling in the adipose tissue of polycystic ovary syndrome. / Chazenbalk, Gregorio; Chen, Yen Hao; Heneidi, Saleh; Lee, Jung Min; Pall, Marita; Chen, Yii Der Ida; Azziz, Ricardo.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 5, 01.05.2012, p. E765-E770.

Research output: Contribution to journalArticle

Chazenbalk, Gregorio ; Chen, Yen Hao ; Heneidi, Saleh ; Lee, Jung Min ; Pall, Marita ; Chen, Yii Der Ida ; Azziz, Ricardo. / Abnormal expression of genes involved in inflammation, lipid metabolism, and Wnt signaling in the adipose tissue of polycystic ovary syndrome. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 5. pp. E765-E770.
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AU - Chen, Yen Hao

AU - Heneidi, Saleh

AU - Lee, Jung Min

AU - Pall, Marita

AU - Chen, Yii Der Ida

AU - Azziz, Ricardo

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N2 - Context: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. Objective: Our objective was to compare gene expression pattern in sc abdominal adipose tissue in nonobese PCOS patients vs. body mass index-matched controls. Research Design and Methods: Eleven PCOS subjects and 12 controls (body mass index 20-28 kg/m2) were recruited. Total RNA was isolated, and gene expression profiling was performed using Affymetrix Human Genome U133 arrays. Differentially expressed genes were classified by gene ontology. Microarray results for selected genes were confirmed by quantitative real-time PCR (RT-qPCR). Frequently sampled iv glucose tolerance tests were used to assess dynamic insulin sensitivity. Results: Ninety-six genes were identified with altered expression of at least 2-fold in nonobese PCOS adipose tissues. Inflammatory response genes were significantly down-regulated. RT-qPCR confirmed decreases in expression of IL6 (12.3-fold), CXCL2(18.3-fold), and SOCS3(22.6-fold). Lipid metabolism genes associated with insulin resistance were significantly up-regulated, with confirmed increases in DHRS9 (2.5-fold), UCLH1 (2.6-fold), and FADS1 (2.8-fold) expression. Wnt signaling genes (DKK2, JUN, and FOSB) were differentially expressed. RT-qPCR confirmed significant expression changes in DKK2 (1.9-fold increase), JUN (4.1-fold decrease), and FOSB (60-fold decrease). Conclusions: Genes involved in inflammation, lipid metabolism, and Wnt signaling are differentially expressed in nonobese PCOS adipose tissue. Because these genes are known to affect adipogenesis and insulin resistance, we hypothesize that their dysregulation may contribute to the metabolic abnormalities observed in women with PCOS.

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