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GLP-1R/GCGR dual agonism dissipates hepatic steatosis to restore insulin sensitivity and rescue pancreatic β-cell function in obese male mice

Early drivers of T2D include ectopic fat accumulation that impairs insulin sensitivity. Here, the authors show that GLP1/GCGR dual agonism provides multimodal benefits in obese male mice by reducing liver fat and improving insulin sensitivity resulting in endogenous β-cell recovery.

Rhianna C. Laker
Shaun Egolf
Christopher J. Rhodes
ResearchOpen Access21 May 2025
Nature Communications

Volume: 16, P: 1-21
Resolution of NASH and hepatic fibrosis by the GLP-1R and GCGR dual-agonist cotadutide via modulating mitochondrial function and lipogenesis

Currently, there is no approved treatment for NAFLD and NASH. Here, Boland et al. show that the GLP-1R and GCGR dual-agonist cotadutide reduces hepatic steatosis, inflammation and fibrosis via GCGR agonism, and glucose homeostasis and weight gain by activating GLP-1 signalling.

Michelle L. Boland
Rhianna C. Laker
Christopher J. Rhodes
Research21 May 2020
Nature Metabolism

Volume: 2, P: 413-431
Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy

Exercise is associated with biogenesis and removal of dysfunctional mitochondria. Here the authors use a mitochondrial reporter gene to demonstrate the occurrence of mitophagy following exercise in mice, and show this is dependent on AMPK and ULK1 signaling.

Rhianna C. Laker
Joshua C. Drake
Zhen Yan
ResearchOpen Access15 Sept 2017
Nature Communications

Volume: 8, P: 1-13
Exercise leads to unfavourable cardiac remodelling and enhanced metabolic homeostasis in obese mice with cardiac and skeletal muscle autophagy deficiency

Zhen Yan
Ana Kronemberger
Vitor A. Lira
ResearchOpen Access11 Aug 2017
Scientific Reports

Volume: 7, P: 1-15

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GLP-1R/GCGR dual agonism dissipates hepatic steatosis to restore insulin sensitivity and rescue pancreatic β-cell function in obese male mice

Resolution of NASH and hepatic fibrosis by the GLP-1R and GCGR dual-agonist cotadutide via modulating mitochondrial function and lipogenesis

Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy

Exercise leads to unfavourable cardiac remodelling and enhanced metabolic homeostasis in obese mice with cardiac and skeletal muscle autophagy deficiency

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