Dietary Phospholipids Ameliorate Fructose-Induced Hepatic Lipid and Metabolic Abnormalities in Rats

Abstract

Overconsumption of fructose results in hepatic dyslipidemia, which has a documented correlation with metabolic syndrome. We examined whether the ingestion of phospholipids (PL) from soybeans prevents fructose-induced metabolic abnormalities. Rats were fed either a fructose-free diet (C), a 60% fructose diet (F), or a 60% fructose plus 3% PL diet (F-PL) for 10 wk. At wk 8, plasma glucose concentrations after glucose loading were significantly higher in rats fed the F diet than in rats fed the C and F-PL diets, which did not differ from one another. The concentrations of hepatic TG, diglycerides, ceramides, and oleates in rats fed the F diet for 10 wk was significantly higher than those in rats fed the C diet. The increases were prevented by concurrent PL ingestion; concentrations did not differ between the F-PL and C groups. Dietary fructose increased the mRNA expression of SREBP1, ChREBP, and genes related to lipogenesis. PL completely inhibited these increases. Furthermore, reflecting the difference at the mRNA level, lipogenic enzyme activities were greater in rats fed the F diet than in rats fed the C diet, and PL ingestion suppressed the increased activities by fructose feeding. Treatment of cultured Hep-G2 cells with fructose for 24 h increased the levels of SREBP1 and ChREBP nuclear proteins, which were suppressed by culture with purified PL components, especially phosphatidylethanolamine and phosphatidylinositol. These findings indicate that PL prevents fructose-induced metabolic abnormalities in association with alterations of the hepatic lipid profile by inhibiting de novo lipogenesis.

Treatment with Ginger Ameliorates Fructose-Induced Fatty Liver and Hypertriglyceridemia in Rats: Modulation of the Hepatic Carbohydrate Response Element-Binding Protein-Mediated Pathway

“…Fructose administration activates ChREBP which acts in synergy with SREBP to increase the expression of lipogenic genes [12, 26–28]. Incubation of HepG2 cells with fructose also induces upregulation of nuclear ChREBP and SREBP1c protein expression [29]. In contrast, SREBP1c is stimulated by insulin [14].…”

“…The relationship between fructose feeding and hepatic expression of PPAR- α and its responsive genes is still controversial. Some studies have reported that fructose feeding downregulated hepatic expression of PPAR- α , CPT1a, and/or ACO genes [18–20, 38], whereas others found no change in the expression of these genes [28, 29, 39–41]. It has been demonstrated that activation of PPAR- α by its agonist fenofibrate strongly induced the expression of hepatic lipogenic genes FAS, ACC1, and SCD1, accompanied by induction of hepatic CPT1a, ACO, and CD36 in mice [42, 43].…”

Advanced glycation end products promote hepatosteatosis by interfering with SCAP-SREBP pathway in fructose-drinking mice

“…Indeed, fructose ingestion at high doses increases expression of the genes encoding for lipogenic enzymes via the activation of SREBP1 in the liver (29). Thus we have analyzed the expression of SREBP1c, SREBP2, and their chaperone protein SCAP in the liver of FRT-and GLC-drinking mice.…”

Fructose, pregnancy and later life impacts

“…Further, although many animal models have used excessively high levels of fructose (30-60% of total energy intake in some cases) not reflective of average human intake, 47,93 these studies have reinforced the adverse effects of excessive fructose consumption. [94][95][96] More recently, animal studies have turned their attention to diets with human intake-relevant fructose loadings (~10% w/v), 81,97-101 predominantly in the rat and mouse. These studies continue to demonstrate fructose-specific metabolic abnormalities, including altered hepatic insulin sensitivity and lipid metabolism.…”