High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes.
High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes.
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高脂肪含量和饱和脂肪酸棕榈酸酯抑制软骨细胞中的IGF-1功能。
DOI：
10.1016/j.joca.2017.05.011
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发表时间：
2017-09
影响因子：
7
通讯作者：
Yammani RR
中科院分区：
文献类型：
--
作者：
Nazli SA;Loeser RF;Chubinskaya S;Willey JS;Yammani RR
Insulin-like growth factor-1 (IGF-1) promotes matrix synthesis and cell survival in cartilage. Chondrocytes from aged and osteoarthritic cartilage have a reduced response to IGF-1. The purpose of this study was to determine the effect of free fatty acids present in a high-fat diet on IGF-1 function in cartilage and the role of ER stress. C57BL/6 male mice were maintained on either a high-fat (60% kcal from fat) or a low-fat (10% kcal from fat) diet for 4 months. Mice were then sacrificed; femoral head cartilage caps were collected and treated with IGF-1 to measure proteoglycan synthesis. Cultured human chondrocytes were treated with 500μM free fatty acids palmitate or oleate, followed by stimulation with (100 ng/ml) IGF-1 overnight to measure CHOP (a protein marker for ER stress) and proteoglycan synthesis. Human chondrocytes were pre-treated with palmitate or 1mM 4-phenyl butyric acid (PBA) or 1μM JNK inhibitor, and IGF-1 function (PG synthesis and signaling) was measured. Cartilage explants from mice on the high fat-diet showed reduced IGF-1 mediated proteoglycan synthesis compared to a low-fat group. Treatment of human chondrocytes with palmitate induced expression of CHOP, activated JNK and inhibited IGF-1function. PBA, a small molecule chemical chaperone that alleviates ER stress rescued IGF-1 function and a JNK inhibitor rescued IGF-1 signaling. Palmitate-induced ER stress inhibited IGF-1 function in chondrocytes/cartilage via activating the MAP kinase JNK. This is the first study to demonstrate that ER stress is metabolic factor that regulates IGF-1 function in chondrocytes.
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影响因子：
13.3
作者：
Yammani, Raghunatha R.;Loeser, Richard F.
通讯作者：
Loeser, Richard F.
影响因子：
27.4
作者：
COLLINS, DH;GHADIALLY, FN;MEACHIM, G
通讯作者：
MEACHIM, G
影响因子：
4.8
作者：
Shimoaka, T;Kamekura, S;Kawaguchi, H
通讯作者：
Kawaguchi, H
影响因子：
--
作者：
Loeser, RF
通讯作者：
Loeser, RF
影响因子：
7
作者：
Chubinskaya, S.;Hakimiyan, A.;Loeser, R. F.
通讯作者：
Loeser, R. F.