Adipocyte accumulation of long-chain fatty acids in obesity is multifactorial, resulting from increased fatty acid uptake and decreased activity of genes involved in fat utilization

José L. Walewski, Fengxia Ge, Michel Gagner, William B. Inabnet, Alfons Pomp, Andrea D. Branch, Paul D. Berk

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Background: The obesity epidemic causes significant morbidity and mortality. Knowledge of cellular function and gene expression in obese adipose tissue will yield insights into obesity pathogenesis and suggest therapeutic targets. The aim of this work is to study the processes determining fat accumulation in adipose tissue from obese patients. Methods: Omental fat was collected from two cohorts of obese bariatric surgery patients and sex-matched normal-weight donors. Isolated adipocytes were compared for cell size, volume, and long-chain fatty acid (LCFA) uptake. Omental fat RNAs were screened by 10K microarray (cohort 1: Three obese, three normal) or Whole Genome microarray (cohort 2: Seven obese, four normal). Statistical differences in gene and pathway expression were identified in cohort 1 using the GeneSifter Software (Geospiza) with key results confirmed in cohort 2 samples by microarray, quantitative real-time polymerase chain reaction, and pathway analysis. Results: Obese omental adipocytes had increased surface area, volume, and V max for saturable LCFA uptake. Dodecenoyl-coenzyme A delta isomerase, central to LCFA metabolism, was approximately 1.6-fold underexpressed in obese fat in cohorts 1 and 2. Additionally, the Kyoto Encyclopedia of Genes and Genomics pathway analysis identified oxidative phosphorylation and fatty acid metabolism pathways as having coordinate, nonrandom downregulation of gene expression in both cohorts. Conclusions: In obese omental fat, saturable adipocyte LCFA uptake was greater than in controls, and expression of key genes involved in lipolysis, β-oxidation, and metabolism of fatty acids was reduced. Thus, both increased uptake and reduced metabolism of LCFAs contribute to the accumulation of LCFAs in obese adipocytes.

Original languageEnglish
Pages (from-to)93-107
Number of pages15
JournalObesity Surgery
Volume20
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • DNA
  • Dodecenoyl-coenzyme A delta isomerase
  • Fatty acid transport
  • Microarrays
  • Obesity
  • Pathways

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