Acute exogenous acyl-GIP treatment enhances lipid handling and fatty acid oxidation by involving brown fat.

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-09-22 DOI:10.1038/s44319-025-00582-7

Sulayman A Lyons, Micah B S Lea, Mihir Parikh, Zhengzhang Guo, Samrin Kagdi, Abigail R Bisnauth, Jonathan R Pitino, Sabrina Ziai, Negar Mir, Aidan D Tyrrell, Yan Fu, Chuck T Chen, Adam H Metherel, Richard P Bazinet, Bin Yang, Patrick J Knerr, Jonathan D Douros, Jonathan E Campbell, Jacqueline L Beaudry

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引用次数: 0

Abstract

The contribution of glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling in brown adipose tissue (BAT) remains underexplored. We studied the acute effects of exogenous acyl-GIP (1 nmol/kg) administration on whole-body lipid handling and fatty acid oxidation, using lipid tolerance tests (LTT) and indirect calorimetry, respectively. We demonstrate that in obese male mice, acute acyl-GIP administration improves lipid tolerance; however, pharmacological inhibition of GIPR, or genetic removal of GIPR globally or with the Myf5-Cre driver, completely abolishes GIP-mediated improvements in lipid tolerance, implicating GIPR in BAT. GIP-mediated improvements in lipid tolerance are associated with an increase in BAT lipid uptake, linked to increases in BAT lipoprotein lipase activity. Our data also reveal that BAT GIPR signalling is necessary for GIP-mediated increases in whole-body fatty acid oxidation, as Myf5-Cre: Gipr mice do not shift substrate oxidation upon GIP administration. Our findings suggest that BAT should be more closely considered in studies examining GIP's effects on whole-body metabolism in rodent models.

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急性外源性酰基- gip治疗通过涉及棕色脂肪增强脂质处理和脂肪酸氧化。

葡萄糖依赖性胰岛素多肽受体（GIPR）信号在棕色脂肪组织（BAT）中的作用仍未得到充分研究。通过脂质耐量试验（LTT）和间接量热法，研究了外源性酰基- gip （1 nmol/kg）对全身脂质处理和脂肪酸氧化的急性影响。我们证明，在肥胖雄性小鼠中，急性酰基- gip可改善脂质耐受性；然而，药物抑制GIPR，或基因去除GIPR或Myf5-Cre驱动，完全消除GIPR介导的脂质耐受性改善，暗示GIPR与BAT有关。gip介导的脂质耐受性的改善与BAT脂质摄取的增加有关，与BAT脂蛋白脂肪酶活性的增加有关。我们的数据还显示，BAT GIPR信号对于GIP介导的全身脂肪酸氧化增加是必要的，因为Myf5-Cre: GIPR小鼠在给予GIP后不会改变底物氧化。我们的研究结果表明，在研究GIP对啮齿动物模型全身代谢的影响时，应该更密切地考虑BAT。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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