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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

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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.

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Acknowledgements

This study was supported by grants DK-52401 and DK-72526 from the National Institute of Diabetes, Digestive and Kidney Disease of the National Institutes of Health and by the Liver Disease Research Fund at Columbia University.

Author information

Author notes

  1. Michel Gagner

    Present address: Department of Surgery, Mount Sinai Medical Center, Miami Beach, FL, 33140, USA

  2. William B. Inabnet

    Present address: Department of Surgery, Mount Sinai Medical Center, New York, NY, 10029, USA

Authors and Affiliations

  1. Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA

    José L. Walewski, Fengxia Ge & Paul D. Berk

  2. Department of Surgery, Weill Cornell Medical College, New York, NY, 10065, USA

    Michel Gagner & Alfons Pomp

  3. Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA

    William B. Inabnet

  4. Department of Medicine, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Andrea D. Branch

  5. Division of Digestive and Liver Diseases, Columbia University Medical Center, Russ Berrie Medical Science Pavilion, 1150 Saint Nicholas Avenue, Room 412, New York, NY, 10032, USA

    Paul D. Berk

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  1. José L. Walewski
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Correspondence to Paul D. Berk.

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Walewski, J.L., Ge, F., Gagner, M. et al. 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. OBES SURG 20, 93–107 (2010). https://doi.org/10.1007/s11695-009-0002-9

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