Mice Lacking Free Fatty Acid Receptor 1 (GPR40/FFAR1) are Protected Against Conjugated Linoleic Acid-Induced Fatty Liver but Develop Inflammation and Insulin Resistance in the Brain
Mice Lacking Free Fatty Acid Receptor 1 (GPR40/FFAR1) are Protected Against Conjugated Linoleic Acid-Induced Fatty Liver but Develop Inflammation and Insulin Resistance in the Brain
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缺乏游离脂肪酸受体 1 (GPR40/FFAR1) 的小鼠可以免受共轭亚油酸诱导的脂肪肝，但大脑中会出现炎症和胰岛素抵抗
DOI：
10.1159/000374031
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发表时间：
2015
影响因子：
--
通讯作者：
Häring HU
中科院分区：
文献类型：
--
作者：
Sartorius T;Drescher A;Panse M;Lastovicka P;Peter A;Weigert C;Wagner R;Kostenis E;Ullrich S;Häring HU
背景/目的共轭亚油酸（CLA）影响体脂分布、诱导胰岛素抵抗和刺激胰岛素分泌。后者的作用是通过游离脂肪酸受体-1（GPR 40/FFAR 1）介导的。本研究探讨GPR 40/FFAR 1是否与组织特异性代谢变化诱导CLAs.Methods和ResultsAfter慢性应用CLAs C57 BL/6 J野生型（WT）和GPR 40/FFAR 1（Ffar 1-/-）敲除小鼠胰岛素抵抗。尽管CLA在肝脏中的累积高达46倍的基因型独立性，但肝脏甘油三酯仅在WT小鼠中增加。这种甘油三酯沉积与炎症增加无关。相比之下，在CLA喂养的Ffar 1-/-小鼠脑中，TNF-α的mRNA水平比WT小鼠脑中高2倍，尽管CLA在脑中的累积不依赖于基因型高达4倍。同时，Ffar 1-/-小鼠对脑室内（icv）胰岛素注射无反应，皮质活动增加，而WT小鼠通过无线电遥测皮质电描记术（ECoG）测量评估有反应。体外培养原代小鼠星形胶质细胞证实CLA刺激神经元炎症反应不依赖于GPR 40/FFAR 1。结论本研究揭示了GPR 40/FFAR 1间接调节CLA的器官特异性效应：功能性GPR 40/FFAR 1的表达对抗CLA诱导的脑炎症反应和胰岛素抵抗，但促进脂肪肝的发生。
Background/AimsConjugated linoleic acids (CLAs) affect body fat distribution, induce insulin resistance and stimulate insulin secretion. The latter effect is mediated through the free fatty acid receptor-1 (GPR40/FFAR1). This study examines whether GPR40/FFAR1 interacts with tissue specific metabolic changes induced by CLAs.Methods and ResultsAfter chronic application of CLAs C57BL/6J wild type (WT) and GPR40/FFAR1 (Ffar1-/-) knockout mice developed insulin resistance. Although CLAs accumulated in liver up to 46-fold genotype-independently, hepatic triglycerides augmented only in WT mice. This triglyceride deposition was not associated with increased inflammation. In contrast, in brain of CLA fed Ffar1-/-mice mRNA levels of TNF-α were 2-fold higher than in brain of WT mice although CLAs accumulated genotype-independently in brain up to 4-fold. Concomitantly, Ffar1-/-mice did not respond to intracerebroventricular (icv) insulin injection with an increase in cortical activity while WT mice reacted as assessed by radiotelemetric electrocorticography (ECoG) measurements. In vitro incubation of primary murine astrocytes confirmed that CLAs stimulate neuronal inflammation independent of GPR40/FFAR1.ConclusionThis study discloses that GPR40/FFAR1 indirectly modulates organ-specific effects of CLAs: the expression of functional GPR40/FFAR1 counteracts CLA-induced inflammation and insulin resistance in the brain, but favors the development of fatty liver.
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游离脂肪酸受体 1 表达的检测：阴性和阳性对照的关键作用
影响因子：
8.2
作者：
Teutsch CA;Panse M;Grundmann M;Kaiser G;Kostenis E;Häring HU;Ullrich S
通讯作者：
Ullrich S
影响因子：
4.8
作者：
Sartorius, Tina;Lutz, Stefan Z.;Hennige, Anita M.
通讯作者：
Hennige, Anita M.
影响因子：
7.7
作者：
Wagner R;Kaiser G;Gerst F;Christiansen E;Due-Hansen ME;Grundmann M;Machicao F;Peter A;Kostenis E;Ulven T;Fritsche A;Häring HU;Ullrich S
通讯作者：
Ullrich S
影响因子：
4.5
作者：
Parra P;Palou A;Serra F
通讯作者：
Serra F
影响因子：
7.7
作者：
Sartorius T;Ketterer C;Kullmann S;Balzer M;Rotermund C;Binder S;Hallschmid M;Machann J;Schick F;Somoza V;Preissl H;Fritsche A;Häring HU;Hennige AM
通讯作者：
Hennige AM