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

Abstract

A high consumption of fat and simple sugars, especially fructose, has been related to the development of insulin resistance, but the mechanisms involved in the effects of these nutrients are not fully understood. This study investigates the effects of a Western-type diet and liquid fructose supplementation, alone and combined, on insulin signalling and inflammation in low-density lipoprotein (LDL) receptor-deficient mice (LDL-R−/−). LDL-R−/− mice were fed chow or Western diet ±15% fructose solution for 12 weeks. Plasma glucose and insulin, and the expression of genes related to inflammation in the liver and visceral white adipose tissue (vWAT), were analysed. V-akt murine thymoma viral oncogene homolog-2 (Akt) activation was measured in the liver of the mice after a single injection of saline or insulin. None of the dietary interventions caused inflammation in vWAT, whereas the Western diet induced hepatic inflammation, which was further enhanced by liquid fructose, leading also to a significant increase in fibrogenesis markers. However, there was no change in plasma glucose or insulin, or insulin-induced Akt phosphorylation. In conclusion, hepatic inflammation and fibrogenesis markers induced by a Western diet supplemented with liquid fructose in LDL-R−/− mice are not associated with a significant impairment of hepatic insulin signalling.

Impairment of Novel Object Recognition Memory and Brain Insulin Signaling in Fructose- but Not Glucose-Drinking Female Rats

“…In contrast, Cigliano et al recently reported hippocampal inflammation in young and adult male rats after short-term consumption of fructose in solid form [44], and suggested that inflammation may be linked to increased intestinal permeability and microbiota remodeling [44,50]. The difference between our results and those from Cigliano et al may lie in the way the body handles solid compared to liquid fructose; thus, we have previously shown that feeding mice with a Western-type solid diet as a source of fructose increases intestinal permeability to bacterial toxins, whereas liquid fructose supplementation (15% w/v) does not [51].…”

Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress

“…Fructose diet increased hepatic levels of proinflammatory cytokines TNFα and IL-1β, while pro-inflammatory IL-6 and anti-inflammatory cytokines IL-4 and IL-10 remained unchanged, consistent with hepatic inflammation [49,50]. The increased hepatic cytokine levels could be mediated by proinflammatory NFκB and JNK signaling pathways in the liver [51].…”

Animal models of diabetes‐associated vascular diseases: an update on available models and experimental analysis

“…Supplementation of liquid fructose to western‐diet fed Ldlr −/− mice demonstrated similar results with the mice developing increased atheromatous plaque driven by increased monocyte/macrophage infiltration and local inflammation. Importantly, atherosclerotic plaque size strongly correlated with plasma lipid levels (Sangüesa et al, 2017). Another method that has been described to model the metabolic syndrome associated with diabetes is the incorporation of low‐dose streptozotocin along with high fat feeding.…”