AdipoRon exerts opposing effects on insulin sensitivity via fibroblast growth factor 21–mediated time-dependent mechanisms |
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| Authors: | Yongliang Wang Huan Liu Ruixin Zhang Yuyao Xiang Junfeng Lu Bo Xia Liang Peng Jiangwei Wu |
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| Affiliation: | 1.Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China;2.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China |
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| Abstract: | 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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| Keywords: | AdipoRon insulin resistance FGF21 glucose and lipid metabolism fatty liver |
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