Changes of Liver Glucose Metabolism in C57BL/6 Mice Transgenic for Human Apolipoprotein ApoCIII

Mice overexpressing the human apolipoprotein apo CIII are a model of dyslipidemia. They become hypertriglyceridemic, hypercholesterolemic and have high blood levels of free fatty acids. Blood glucose is normal, but as the liver integrates lipid and carbohydrate metabolism, conditions of high inter-tissue circulation of energy substrates, such as fasting, may reveal hepatic alterations of glucose metabolism in these (CIII) mice. This hypothesis was explored by in situ liver perfusion in this investigation. The NTG (non-transgenic) animals showed liver and muscle glycogen content changes compatible with the fed or fasted state. In contrast, glycogen in group CIII was much lower in the fed state. The liver glucose release in group CIII after overnight fasting and adrenaline-stimulated was lower than in group NTG. Total glucose production under gluconeogenic conditions was not different between groups NTG and CIII, but glucose production from alanine was decreased in group CIII. Therefore, dyslipidemia caused by overexpression of apoCIII in mice alters the liver glucose metabolism, particularly compromising glycogen synthesis and degradation. This profile might have adverse outcomes during metabolic challenges that are more severe than fasting.