Genes and networks expressed in perioperative omental adipose tissue are correlated with weight loss from Roux-en-Y gastric bypass

Abstract

Context: Gastric bypass surgery is the most commonly performed bariatric surgical procedure in the United States. Variable weight loss following this relatively standardized intervention has been reported. To date, a method for reliable profiling of patients who will successfully sustain weight loss for the long term has not been established. In addition, the mechanisms of action in accomplishing major weight loss as well as the explanation for the variable weight loss have not been established. Objective: To examine whether gene expression in perioperative omental adipose is associated with gastric bypass-induced weight loss. Design: Cross-sectional study of gene expression in perisurgical omental adipose tissues taken/available at the time of operation and total excess weight loss (EWL). Subjects: Fifteen overweight individuals who underwent Roux-en-Y gastric bypass (RYGB) surgery at the University of California Davis Medical Center (BMI: 40.6-72.8 kg/m 2 ). Measurements: Body weight before and following weight stabilization 18-42 months after surgery. Perioperative omental adipose RNA isolated from 15 subjects was hybridized to Affymetrix HG-U133A chips for 22 283 transcript expression measurements. Results: Downstream analysis identified a set of genes whose expression was significantly correlated with RYGB-induced weight loss. The significant individual genes include acyl-coenzyme A oxidase 1 (ACOX1), phosphodiesterase 3A cGMP-inhibited (PDE3A) and protein kinase, AMP-activated, beta 1 non-catalytic subunit (PRKAB1). Specifically, ACOX1 plays a role in fatty acid metabolism. PDE3A is involved in purine metabolism and hormone-stimulated lipolysis. PRKAB1 is involved in adipocytokine signaling pathway. Gene network analysis revealed that pathways for glycerolipid metabolism, breast cancer and apoptosis were significantly correlated with long-term weight loss. Conclusion: This study demonstrates that RNA expression profiles from perioperative adipose tissue are associated with weight loss outcome following RYGB surgery. Our data suggest that EWL could be predicted from preoperative samples, which would allow for informed decisions about whether or not to proceed to surgery.

Changes in Gene Expression Profile in Human Subcutaneous Adipose Tissue during Significant Weight Loss

“…Gene network analysis applied to obesity and caloric restriction, e.g. following bariatric surgery, highlighted the importance of pathways for glycerolipid metabolism (reviewed in [6,7]). Peroxisome proliferator-activated receptor-γ 1 and 2 ( PPAR γ 1 and 2 ) and 11β-hydroxysteroid dehydrogenase type 1 ( 11 β HSD1 ) are among the glycerolipid metabolism-related genes.…”

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

“…Each of these underexpressed genes plays a role in the metabolism of LCFA, and several have already been reported to play a role in obesity. Acyl-coenzyme A oxidase 1 (1.3.3.6) expression in omental fat reportedly predicts weight loss outcome after gastric bypass surgery [54]. DCI (5.3.3.8), grouped with 3-hydroxyacyl-coenzyme A dehydrogenase (1.1.1.35), plays a key role in LCFA degradation (discussed above).…”

Expectations, validity, and reality in gene expression profiling

“…DNA microarray experiments are typically designed to achieve one or several of the following objectives: (1) to identify individual genes (transcripts) whose expression is correlated with a phenotypic trait such as response to treatment, (2) to identify multiple genes that are interactively involved in regulatory networks and mediating biological phenomena or disease pathogenesis, (3) to discover potential molecular targets for drug development, and (4) to identify molecular markers that can be used as tools for disease diagnosis and prognosis or as predictors of clinical outcomes. Regardless of the purpose of a microarray study, there is one common underlying assumption—the primary end point of the study is associated with the expression levels of a number of genes.…”

“…Regardless of the purpose of a microarray study, there is one common underlying assumption—the primary end point of the study is associated with the expression levels of a number of genes. For example, Kim et al profiled genes from perioperative adipose tissue whose expression was associated with weight loss outcome following Roux-en-Y gastric bypass (RYGB) surgery (4). Their results showed that genes for glycerolipid syntheses that are directly involved in regulating adipose tissue fat stores were significantly correlated with postoperative body weight loss.…”

“…In 2001 the MGED in turn created the Minimum Information About a Microarray Experiment (MIAME) guidelines which serve as a template for researchers to report an adequate description of how microarray data were obtained. The MIAME has six essential elements (68): (1) Experimental design; (2) Type of array and description of each element on the array; (3) Description of samples and their preparation and labeling procedures; (4) Hybridization procedures and parameters; (5) Images and description of measurement specifications; (6) Description of normalization procedures. Currently, many journals require MIAME compliance as a part of the manuscript submitting procedure.…”