AdipoRon exerts opposing effects on insulin sensitivity via fibroblast growth factor 21-mediated time-dependent mechanisms.

AdipoRon exerts opposing effects on insulin sensitivity via fibroblast growth factor 21-mediated time-dependent mechanisms.
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DOI:
10.1016/j.jbc.2022.101641
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发表时间:
2022-03
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Wu J
Wu J
中科院分区:
其他
文献类型:
--
作者:
Wang Y;Liu H;Zhang R;Xiang Y;Lu J;Xia B;Peng L;Wu J

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越来越多的证据表明,合成的脂联素受体激动剂AdipoRon参与全身胰岛素敏感性和能量稳态的调节。然而,这些改变的机制仍不清楚。在这里,使用高胰岛素-正葡萄糖钳夹和同位素示踪技术,我们表明短期(10天)AdipoRon给药通过增加高脂饮食小鼠成纤维细胞生长因子21的循环水平间接抑制白色脂肪组织的脂解。这导致血浆游离脂肪酸浓度降低,并改善脂质诱导的全身胰岛素抵抗。相比之下,我们发现长期(20天)AdipoRon给药直接加剧了白色脂肪组织的脂解,增加了肝脏的再生,并损害了骨骼肌中的三羧酸循环,导致全身胰岛素抵抗加重。总之,这些数据提供了新的见解AdipoRon多方面的功能复杂性的全面理解.
Increasing evidence has shown that AdipoRon, a synthetic adiponectin receptor agonist, is involved in the regulation of whole-body insulin sensitivity and energy homeostasis. However, the mechanisms underlying these alterations remain unclear. Here, using hyperinsulinemic–euglycemic clamp and isotopic tracing techniques, we show that short-term (10 days) AdipoRon administration indirectly inhibits lipolysis in white adipose tissue via increasing circulating levels of fibroblast growth factor 21 in mice fed a high-fat diet. This led to reduced plasma-free fatty acid concentrations and improved lipid-induced whole-body insulin resistance. In contrast, we found that long-term (20 days) AdipoRon administration directly exacerbated white adipose tissue lipolysis, increased hepatic gluconeogenesis, and impaired the tricarboxylic acid cycle in the skeletal muscle, resulting in aggravated whole-body insulin resistance. Together, these data provide new insights into the comprehensive understanding of multifaceted functional complexity of AdipoRon.
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