Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery

• Type of Material: Article
• Authors: Cyrus Jahansouz, University of Minnesota; Hongliang Xu, University of Minnesota; Ann V. Hertzel, University of Minnesota; Scott S. Kizy, University of Minnesota; Kaylee A. Steen, University of Minnesota; Rocio Foncea, University of Minnesota; Federico Serrot, Emory University; Nicholas Kvalheim, University of Minnesota; Girish Luthra, Park Nicollet Bariatric Surgery Center; Kristin Ewing, CentraCare Bariatric Center; Daniel B. Leslie, University of Minnesota; Sayeed Ikramuddin, University of Minnesota; David A. Bernlohr, University of Minnesota
• Language: English
• Date: 2018-02-01
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017, Springer Nature
• Final Published Version (URL): http://dx.doi.org/10.1038/ijo.2017.197
• Title of Journal or Parent Work: International Journal of Obesity
• ISSN: 0307-0565
• Volume: 42
• Issue: 2
• Start Page: 139
• End Page: 146
• Grant/Funding Information: This work was supported by the American Diabetes Association (ADA 7-11-ST-01), NIH DK053189 to DAB and the Minnesota Obesity Center (NIH P30DK050456).
• Keywords: INSULIN-RESISTANCE; GASTRIC BYPASS; FATTY-ACID; Endocrinology & Metabolism; ACTIVATED-RECEPTOR-GAMMA; WEIGHT-LOSS; HEPATIC GLUCOSE-PRODUCTION; ACID-BINDING PROTEIN; Science & Technology; OBESITY; DECREASED RISK; Life Sciences & Biomedicine; Nutrition & Dietetics; COMMON POLYMORPHISM
• Research Categories: Health Sciences, Medicine and Surgery; Chemistry, Biochemistry

Abstract

Background:Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined.Materials and Methods:Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, β-oxidation, lipolysis and cysteine oxidation.Results:Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPAR3 and PPAR in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPAR3/ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery.Conclusions:These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.