Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity

Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity
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DOI:
10.1113/jphysiol.2009.184754
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发表时间:
2010-06-15
影响因子:
5.5
通讯作者:
Dela, Flemming
Dela, Flemming
中科院分区:
医学1区
文献类型:
--
作者:
Kraunsoe, Regitze;Boushel, Robert;Dela, Flemming

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脂肪组织在健康和疾病中发挥重要的内分泌和代谢功能。然而,该组织的生物能量学在人类中没有特征,可能的区域差异也没有得到阐明。使用高分辨率呼吸测定法,对20名接受减肥手术的肥胖患者的活检组织中的人腹部皮下和腹内内脏(大网膜)脂肪组织中的线粒体呼吸进行定量。用PCR技术测定线粒体DNA(mtDNA)和基因组DNA(gDNA),以估计线粒体密度。将脂肪组织样品透化,并在37 ℃下一式两份进行呼吸测量。依次加入底物(谷氨酸盐(G)+苹果酸盐(M)+辛酰基肉毒碱(O)+琥珀酸盐(S))以向络合物I + II提供电子。在GM之后添加用于状态3呼吸的ADP((D))。在添加FCCP后测量解偶联呼吸。每毫克组织中内脏脂肪比皮下脂肪含有更多的线粒体,但细胞较小。在两种组织中均发现了稳健、稳定的氧通量,并且耦合状态3(GMOS(D))和非耦合呼吸显著降低,(P <0.05)(分别为0.95 +/-0.05和1.15 +/-0.06 pmol O-2 s-1 mg-1)与皮下(分别为0.76 +/-0.04和0.98 +/-0.05 pmol O-2 s-1 mg-1)脂肪组织相比。内脏脂肪组织的线粒体呼吸显著降低(P <0.05)。与皮下脂肪组织相比,内脏脂肪组织的底物控制率较高,解偶联控制率较低(P <0.05)。我们的结论是,内脏脂肪是生物能量更活跃,更敏感的线粒体底物供应比皮下脂肪。与皮下脂肪组织相比,内脏组织中的氧化磷酸化具有更高的相对活性。
Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O-2 s-1 mg-1, respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O-2 s-1 mg-1, respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.