Liquid fructose in Western-diet-fed mice impairs liver insulin signaling and causes cholesterol and triglyceride loading without changing calorie intake and body weight

Abstract

LFS in mice, in a background of an unhealthy diet that already induces fatty liver visceral fat accretion and obesity, increases liver lipid burden, hinders hepatic insulin signaling and diminishes whole-body insulin sensitivity without changing energy intake.

The Addition of Liquid Fructose to a Western-Type Diet in LDL-R−/− Mice Induces Liver Inflammation and Fibrogenesis Markers without Disrupting Insulin Receptor Signalling after an Insulin Challenge

“…This is in agreement with our previous observation of increased CD36 mRNA expression in WF-LDL-R −/− mice [18]. In contrast, our recent study performed in wild type C57BL/6N mice, showed no signs of hepatic inflammation despite a significant increase in hepatic cholesterol deposition in W and WF groups [17]. To compare the hepatic cholesterol deposition between wild type and knockout mice, we used data from [17,18], and expressed them as mg of cholesterol per gram protein.…”

“…However, it has been suggested that insulin sensitivity is not reduced when the inflammation is restricted to the liver compartment and does not affect adipose tissue [1,11,41]. Our results are in accordance with this hypothesis, as LDL-R −/− mice show no signs of inflammation in vWAT (Figure 1), whereas in our previous study in wild type mice we observed inflammation in vWAT but not in the liver, and whole-body insulin sensitivity was significantly reduced [17]. …”

“…In contrast, our recent study performed in wild type C57BL/6N mice, showed no signs of hepatic inflammation despite a significant increase in hepatic cholesterol deposition in W and WF groups [17]. To compare the hepatic cholesterol deposition between wild type and knockout mice, we used data from [17,18], and expressed them as mg of cholesterol per gram protein. This is more accurate for comparison, due to the significant increase in liver weight observed in LDL-R −/− mice from the WF group, but not in wild-type mice.…”

“…However, unhealthy human dietary patterns frequently include not only excessive added sugars, but also excessive fat intake, particularly saturated fats [16]. For this reason, in a recent publication we explored the effects of liquid fructose supplementation to C57BL/6N mice in two different solid diets, a standard rodent chow and a Western-type rodent chow rich in saturated fat, refined carbohydrates and cholesterol [17]. Our results showed that in this model liquid fructose supplementation increased liver triglyceride and cholesterol levels and diminished whole-body insulin sensitivity only when it was combined with a Western-type diet; however, these effects were not associated with a clear inflammatory reaction in the liver [17].…”

“…For this reason, in a recent publication we explored the effects of liquid fructose supplementation to C57BL/6N mice in two different solid diets, a standard rodent chow and a Western-type rodent chow rich in saturated fat, refined carbohydrates and cholesterol [17]. Our results showed that in this model liquid fructose supplementation increased liver triglyceride and cholesterol levels and diminished whole-body insulin sensitivity only when it was combined with a Western-type diet; however, these effects were not associated with a clear inflammatory reaction in the liver [17]. We also studied the effects of these diets on the development of aortic atherosclerotic lesions in low-density lipoprotein (LDL) receptor-deficient (LDL-R −/− ) mice [18].…”