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

Abstract

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.

Moderate-intensity continuous training reduces triglyceridemia and improves oxygen consumption in dyslipidemic apoCIII transgenic mice

“…Studies also show that a decrease in muscle glycogen content compromises exercise performance ( 36 ). Previously, we showed that 4-month-old CIII animals have less glycogen than their NTG controls ( 18 ). However, this difference was not found in the sedentary 15-month-old animals, showing that aging in this animal model may also modify their glycogen metabolism.…”

“…Genotyping was confirmed by measuring basal triglyceride levels after a 12-h overnight fast. Animals with triglyceride levels lower than 100 mg/dL were considered NTG and animals with triglyceride levels higher than 300 mg/dL were considered transgenic (CIII) ( 17 - 19 ).…”