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doi: 10.1021/bi701559f 82 LennickeCCochemeHM

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Glucagon Receptor Engagement Energy Expenditure and Hepatic Metabolism Although GLP3 exhibits lower potency at glucagon receptors compared to native glucagon, this component of its triagonist mechanism appears critical for its metabolic effects[8]: Increased energy expenditure through thermogenic activation Enhanced hepatic fatty acid oxidation and reduced hepatic steatosis Modulation of hepatic glucose production during fasted states Promotion of lipolysis in adipose tissue Potential effects on lean mass preservation through metabolic adaptations In vitro studies demonstrated that GLP3 achieves efficacy similar to natural glucagon in stimulating glucose production in hepatocytes, while in adipocytes it surpasses native GIP in inducing lipolysis[9]