Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery.
Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery.
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DOI：
10.1038/ijo.2017.197
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Bernlohr DA
中科院分区：
文献类型：
--
作者：
Jahansouz C;Xu H;Hertzel AV;Kizy S;Steen KA;Foncea R;Serrot FJ;Kvalheim N;Luthra G;Ewing K;Leslie DB;Ikramuddin S;Bernlohr DA
减肥手术仍然是减少肥胖和消除2型糖尿病的最有效的治疗方法，但责任机制(S)仍然不清楚。过氧化物酶体增殖物激活受体(PPAR)是一类核激素受体，激活后可控制脂代谢、血糖调节和炎症反应。它们在减肥手术后脂肪组织中的作用仍未确定。随机分为Roux-en-Y胃旁路手术组(n=13)、匹配热量限制组(n=14)和垂直袖状胃切除术组(n=33)，分别于手术时和术后第7天对患者皮下脂肪组织活检和血清进行评估。对脂肪样本的基因表达、蛋白质水平、β氧化、脂解和半胱氨酸氧化的变化进行了评估。在7天内，减肥手术急剧改变了皮下脂肪组织中PPARγ和PPARδ的活性和表达，从而减少了脂肪储存，增加了脂肪分解，增强了脂质氧化。这种独特的代谢变化导致了PPAR下游γ/δ靶点的变化，包括FABP4和SCD1mRNA的表达降低，而肉碱棕榈酰转移酶1和解偶联蛋白2的表达增加。UCP2的表达增加不仅促进了脂肪酸的氧化(手术后增加了15倍)，而且通过减弱蛋白质半胱氨酸的氧化和减少氧化应激来调节皮下脂肪组织的氧化还原体。手术后，UCP1的表达没有改变。UCP1是一种线粒体蛋白，负责调节米色和棕色脂肪中的脂肪酸氧化和产热。这些结果表明，减肥手术通过调节PPAR亚型，在皮下脂肪组织中启动了一种新的代谢转变，以独立于发色过程氧化脂肪酸。需要进一步的研究来了解这种PPAR亚型表达的变化对减肥手术后体重减轻的贡献。
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. Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from at 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. Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of FABP4 and 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. 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 as a contributor to weight loss following bariatric surgery.
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