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Long-term high intake of 9-PAHPA or 9-OAHPA increases basal metabolism and insulin sensitivity but disrupts liver homeostasis in healthy mice.
The Journal of Nutritional Biochemistry ( IF 4.8 ) Pub Date : 2020-02-22 , DOI: 10.1016/j.jnutbio.2020.108361
Melha Benlebna 1 , Laurence Balas 2 , Béatrice Bonafos 1 , Laurence Pessemesse 1 , Claire Vigor 2 , Jacques Grober 3 , Florence Bernex 4 , Gilles Fouret 1 , Veronika Paluchova 5 , Sylvie Gaillet 1 , Jean François Landrier 6 , Ondrej Kuda 5 , Thierry Durand 2 , Charles Coudray 1 , François Casas 1 , Christine Feillet-Coudray 1
Affiliation  

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a new family of endogenous lipids recently discovered. Several studies reported that some FAHFAs have antidiabetic and anti-inflammatory effects. The objective of this study was to explore the impact of two FAHFAs, 9-PAHPA or 9-OAHPA, on the metabolism of mice. C57Bl/6J male mice, 6 weeks old, were divided into 3 groups of 10 mice each. One group received a control diet and the two others groups received the control diet supplemented with 9-PAHPA or 9-OAHPA for 12 weeks. Mouse weight and body composition were monitored throughout the study. Some days before euthanasia, energy expenditure, glucose tolerance and insulin sensitivity were also determined. After sacrifice, blood and organs were collected for relevant molecular, biochemical and histological analyses. Although high intake of 9-PAHPA or 9-OAHPA increased basal metabolism, it had no direct effect on body weight. Interestingly, the 9-PAHPA or 9-OAHPA intake increased insulin sensitivity but without modifying glucose tolerance. Nevertheless, 9-PAHPA intake induced a loss of glucose-stimulated insulin secretion. Surprisingly, both studied FAHFAs induced hepatic steatosis and fibrosis in some mice, which were more marked with 9-PAHPA. Finally, a slight remodeling of white adipose tissue was also observed with 9-PAHPA intake. In conclusion, the long-term high intake of 9-PAHPA or 9-OAHPA increased basal metabolism and insulin sensitivity in healthy mice. However, this effect, highly likely beneficial in a diabetic state, was accompanied by manifest liver damage in certain mice that should deserve special attention in both healthy and pathological studies.



中文翻译:

长期大量摄入9-PAHPA或9-OAHPA可增加基础小鼠的基础代谢和胰岛素敏感性,但会破坏健康小鼠的肝脏体内稳态。

羟基脂肪酸的支链脂肪酸酯(FAHFA)是最近发现的新的内源脂质家族。几项研究报告说,某些FAHFA具有抗糖尿病和抗炎作用。这项研究的目的是探讨两种FAHFA(9-PAHPA或9-OAHPA)对小鼠代谢的影响。将6周大的C57Bl / 6J雄性小鼠分成3组,每组10只。一组接受对照饮食,另外两组接受补充9-PAHPA或9-OAHPA的对照饮食,持续12周。在整个研究中监测小鼠的体重和身体组成。安乐死前几天,还确定了能量消耗,葡萄糖耐量和胰岛素敏感性。处死后,收集血液和器官进行相关的分子,生化和组织学分析。尽管高摄入9-PAHPA或9-OAHPA可以增加基础代谢,但对体重没有直接影响。有趣的是,摄入9-PAHPA或9-OAHPA可以增加胰岛素敏感性,但不会改变葡萄糖耐量。然而,摄入9-PAHPA会导致葡萄糖刺激的胰岛素分泌减少。出人意料的是,这两个研究均在一些小鼠中研究了FAHFA诱导的肝脂肪变性和纤维化,其中9-PAHPA更为明显。最后,在摄入9-PAHPA时还观察到白色脂肪组织的轻微重塑。总之,长期摄入高剂量的9-PAHPA或9-OAHPA可增加健康小鼠的基础代谢和胰岛素敏感性。但是,这种作用在糖尿病患者中很有可能是有益的,

更新日期:2020-02-22
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