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Disease or injury models can alter inflammation, metabolism, tissue vulnerability, mortality risk, and remodeling, which limits how broadly safety-related observations can be generalized

ROS Overproduction: The Initiating Driver Hyperglycaemia activates multiple simultaneous ROS sources, including mitochondrial uncoupling, NADPH oxidase isoforms NOX2 and NOX4, and xanthine oxidase upregulation

IL-6, which is also increased in obesity (176, 183) can stimulate lipolysis (184) and cause hyperglycemia and hepatic insulin resistance in rats (183) and requires intact JNK signaling in macrophages (183) to promote diet-induced insulin resistance (185)

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