Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Int J Obes (Lond). 2018 Feb;42(2):139-146. doi: 10.1038/ijo.2017.197. Epub 2017 Aug 14.
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 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 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.
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.
减重手术仍然是减少肥胖和消除 2 型糖尿病最有效的治疗方法；然而，其作用机制仍难以捉摸。过氧化物酶体增殖物激活受体（PPAR）是一类核激素受体，其在激活后可控制脂质代谢、葡萄糖调节和炎症。它们在减重手术后脂肪组织中的作用尚未确定。
从接受 Roux-en-Y 胃旁路术（n=13）或匹配热量限制（n=14）的患者以及接受垂直袖状胃切除术（n=33）的患者手术时和术后第 7 天获得并评估皮下脂肪组织活检和血清。评估脂肪样本中基因表达、蛋白质水平、β-氧化、脂肪分解和半胱氨酸氧化的变化。
在 7 天内，减重手术急性改变皮下脂肪组织中 PPARγ 和 PPARδ 的活性和表达，从而减少脂肪储存、增加脂肪分解和增强脂肪氧化。这种独特的代谢改变导致下游 PPARγ/δ 靶标表达的变化，包括脂肪酸结合蛋白（FABP）4 和硬脂酰辅酶 A 去饱和酶-1（SCD1）表达降低，肉碱棕榈酰转移酶 1（CPT1）和解偶联蛋白 2（UCP2）表达增加。UCP2 的表达增加不仅促进脂肪酸氧化（手术后增加 15 倍），而且通过减轻蛋白质半胱氨酸氧化和降低氧化应激来调节皮下脂肪组织的氧化还原组。UCP1 的表达不变，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，减重手术在皮下脂肪组织中引发了一种新的代谢转变，通过调节 PPAR 同工型，使脂肪酸氧化独立于褐变过程。需要进一步的研究来了解这种 PPAR 同工型表达转变对减重手术后体重减轻的贡献。
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