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:
影响因子:
--
通讯作者:
Wu J
中科院分区:
文献类型:
--
作者:
Wang Y;Liu H;Zhang R;Xiang Y;Lu J;Xia B;Peng L;Wu J
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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