Downregulation of adipose tissue fatty acid trafficking in obesity: a driver for ectopic fat deposition?
Downregulation of adipose tissue fatty acid trafficking in obesity: a driver for ectopic fat deposition?
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作者：
McQuaid SE;Hodson L;Neville MJ;Dennis AL;Cheeseman J;Humphreys SM;Ruge T;Gilbert M;Fielding BA;Frayn KN;Karpe F
脂肪毒性和异位脂肪沉积减少胰岛素信号传导。目前尚不清楚非脂肪组织中的过量脂肪沉积是由脂肪组织的过量脂肪酸输送引起的，还是由摄入脂肪的脂肪组织储存受损引起的。为了研究这一点，我们使用了全身综合生理学方法，同时使用多种稳定同位素脂肪酸示踪剂，以评估瘦男性（n = 9）和腹部肥胖男性（n = 10）在昼夜周期内脂肪组织中内源性和外源性脂肪酸的输送和转运。腹部肥胖男性的脂肪组织质量比瘦对照组高出2.5倍，但非酯化脂肪酸（NEFA）的释放率下调，导致24小时内全身NEFA浓度正常。然而，在肥胖男性中，餐后脂肪组织脂肪储存显著降低。这对于乳糜微粒衍生的脂肪酸尤其如此，代表膳食脂肪的直接储存途径。来自肥胖男性的脂肪组织显示出与这种受损的脂肪储存功能一致的转录特征。脂肪组织质量的增加导致全身NEFA递送的适当下调，同时维持血浆NEFA浓度。然而，脂肪组织脂肪酸摄取的隐性减少超出了这一点，并显示出适应不良反应，直接膳食脂肪储存途径严重受损。这种脂肪组织对肥胖的反应可能为异位脂肪沉积和脂毒性提供了病理生理学基础。
Lipotoxicity and ectopic fat deposition reduce insulin signaling. It is not clear whether excess fat deposition in nonadipose tissue arises from excessive fatty acid delivery from adipose tissue or from impaired adipose tissue storage of ingested fat. To investigate this we used a whole-body integrative physiological approach with multiple and simultaneous stable-isotope fatty acid tracers to assess delivery and transport of endogenous and exogenous fatty acid in adipose tissue over a diurnal cycle in lean (n = 9) and abdominally obese men (n = 10). Abdominally obese men had substantially (2.5-fold) greater adipose tissue mass than lean control subjects, but the rates of delivery of nonesterified fatty acids (NEFA) were downregulated, resulting in normal systemic NEFA concentrations over a 24-h period. However, adipose tissue fat storage after meals was substantially depressed in the obese men. This was especially so for chylomicron-derived fatty acids, representing the direct storage pathway for dietary fat. Adipose tissue from the obese men showed a transcriptional signature consistent with this impaired fat storage function. Enlargement of adipose tissue mass leads to an appropriate downregulation of systemic NEFA delivery with maintained plasma NEFA concentrations. However the implicit reduction in adipose tissue fatty acid uptake goes beyond this and shows a maladaptive response with a severely impaired pathway for direct dietary fat storage. This adipose tissue response to obesity may provide the pathophysiological basis for ectopic fat deposition and lipotoxicity.
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影响因子：
8.2
作者：
Bickerton, A. S. T.;Roberts, R.;Frayn, K. N.
通讯作者：
Frayn, K. N.
影响因子：
7.7
作者：
Bickerton, Alex S. T.;Roberts, Rachel;Frayn, Keith N.
通讯作者：
Frayn, Keith N.
DOI：
10.1002/dmr.5610040607
发表时间：
1988-09-01
期刊：
DIABETES-METABOLISM REVIEWS
影响因子：
--
作者：
BJORNTORP, P
通讯作者：
BJORNTORP, P
影响因子：
5.8
作者：
Heptulla, R;Smitten, A;Caprio, S
通讯作者：
Caprio, S
影响因子：
5.8
作者：
Ruge, Toralph;Hodson, Leanne;Karpe, Fredrik
通讯作者：
Karpe, Fredrik