Blanchard P G, Turcotte V, Côté M, Gélinas Y, Nilsson S, Olivecrona G, Deshaies Y, Festuccia W T
Department of Medicine, Faculty of Medicine, Quebec Heart and Lung Institute, Laval University, Quebec, QC, Canada.
Department of Medical Biosciences/Physiological Chemistry, Umeå University, Umeå, Sweden.
Acta Physiol (Oxf). 2016 Jul;217(3):227-39. doi: 10.1111/apha.12665. Epub 2016 Mar 12.
Peroxisome proliferator-activated receptor (PPAR) γ activation is associated with preferential lipoprotein lipase (LPL)-mediated fatty acid storage in peripheral subcutaneous fat depots. How PPARγ agonism acts upon the multi-level modulation of depot-specific lipid storage remains incompletely understood.
We evaluated herein triglyceride-derived lipid incorporation into adipose tissue depots, LPL mass and activity, mRNA levels and content of proteins involved in the modulation of LPL activity and fatty acid transport, and the expression/activity of enzymes defining adipose tissue lipogenic potential in rats treated with the PPARγ ligand rosiglitazone (30 mg kg(-1) day(-1) , 23 days) after either a 10-h fasting period or a 17-h fast followed by 6 h of ad libitum refeeding.
Rosiglitazone stimulated lipid accretion in subcutaneous fat (SF) ~twofold and significantly reduced that of visceral fat (VF) to nearly half. PPARγ activation selectively increased LPL mass, activity and the expression of its chaperone LMF1 in SF. In VF, rosiglitazone had no effect on LPL activity and downregulated the mRNA levels of the transendothelial transporter GPIHBP1. Overexpression of lipid uptake and fatty acid transport proteins (FAT/CD36, FATP1 and FABP4) and stimulation of lipogenic enzyme activities (GPAT, AGPAT and DGAT) upon rosiglitazone treatment were of higher magnitude in SF.
Together these findings demonstrate that the depot-specific transcriptional control of LPL induced by PPARγ activation extends to its key interacting proteins and post-translational modulators to favour subcutaneous lipid storage.
过氧化物酶体增殖物激活受体（PPAR）γ激活与脂蛋白脂肪酶（LPL）介导的脂肪酸优先储存于外周皮下脂肪库有关。PPARγ激动剂如何作用于特定储存库脂质储存的多层次调节仍不完全清楚。
我们在此评估了用PPARγ配体罗格列酮（30mg kg⁻¹ 天⁻¹，23天）处理的大鼠在禁食10小时或禁食17小时后再自由进食6小时后，甘油三酯衍生的脂质掺入脂肪组织库、LPL质量和活性、参与调节LPL活性和脂肪酸转运的蛋白质的mRNA水平和含量，以及定义脂肪组织生脂潜力的酶的表达/活性。
罗格列酮刺激皮下脂肪（SF）中的脂质积聚增加约两倍，并将内脏脂肪（VF）的脂质积聚显著降低至近一半。PPARγ激活选择性地增加了SF中LPL的质量、活性及其伴侣LMF1的表达。在VF中，罗格列酮对LPL活性没有影响，并下调了跨内皮转运蛋白GPIHBP1的mRNA水平。罗格列酮处理后，脂质摄取和脂肪酸转运蛋白（FAT/CD36、FATP1和FABP4）的过表达以及生脂酶活性（GPAT、AGPAT和DGAT）的刺激在SF中更为显著。
这些发现共同表明，PPARγ激活诱导的LPL在特定储存库的转录控制延伸至其关键相互作用蛋白和翻译后调节剂，以促进皮下脂质储存。
