Hepatic Adverse Effects of Fructose Consumption Independent of Overweight/Obesity

Abstract

The chronic intake of fructose has been linked to insulin resistance, obesity, dyslipidemia and nonalcoholic fatty liver disease (NAFLD), which in turn, may progress to nonalcoholic steatohepatitis (NASH). We aimed to evaluate the magnitude of the effects of the chronic consumption of high-fructose (HFr) and high fat (HF) alone or combined. Four groups of male mice were fed different diets for 16 weeks: standard chow (9% fat: SC), HF diet (42% fat), HFr diet (34% fructose) and HF/HFr diet (42% fat, 34% fructose). The food intake was not different among the groups, and the body mass was not greater in the HFr group than in the SC group. The homeostasis model assessment for insulin resistance (HOMA-IR), as well as plasmatic total cholesterol and triglycerides were greater in the groups HF, HFr, and HF/HFr group than in the SC group. We observed in the groups HF, HFr and HF/HFr, compared to the group SC, nonalcoholic fatty liver disease (NAFLD) with a predominance of lipogenesis mediated by SREBP-1c and PPAR-γ, and a reduction of the oxidation mediated by PPAR-α. We also observed an increase in gluconeogenesis mediated by the GLUT-2 and the PEPCK. Importantly, we identified areas of necroinflammation indicating a transition from NAFLD to nonalcoholic steatohepatitis in the HFr and HF/HFr groups. This study is relevant in demonstrating that fructose consumption, even in the absence of obesity, causes serious and deleterious changes in the liver with the presence of the dyslipidemia, insulin resistance (IR), and NAFLD with areas of necroinflammation. These conditions are associated with a poor prognosis.

Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

“…PPARg expression is mainly limited to the adipocyte, but under conditions of chronic hepatic lipid accumulation, the liver expresses considerable amounts of PPARg (VidalPuig et al 1996, Pettinelli & Videla 2011, Schultz et al 2013, Barbosa-da-Silva et al 2015. Both PPARa and PPARg recognize the same fatty acids and eicosanoids ligands (Xu et al 1999).…”

Effect of inulin supplementation in male mice fed with high fat diet on biochemical profile and α-amylase gene expression

“…Fructose was previously suggested as an alternate sweetener to saccharin [9], and assumed to be a safe product when consumed moderately [10]. However, recent studies highlight the occurrence of severe adverse effects linked to its consumption [11,12]. On the other hand, inulin is considered as a "dietary fiber" which could be proposed as a potentially healthier alternative to fructose [13].…”

Lipogenesis in Huh7 cells is promoted by increasing the fructose: Glucose molar ratio

“…Because fructose metabolism is insulin-independent and does not stimulate pancreatic insulin secretion [28] , this monosaccharide was previously thought to be a superior dietary substrate, as compared with other sugars [29] . However, more recent experimental data, while confirming these metabolic characteristics, also demonstrate fructose promotion of insulin resistance [12] .…”