Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague–Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression

Sangüesa, Gemma; Montañés, José Carlos; Baena, Miguel; Sánchez, Rosa María Galán; Roglans, Núria; Alegret, Marta; Laguna, Juan C.

doi:10.1007/s00394-018-1654-9

Cited by 12 publications

(32 citation statements)

References 55 publications

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“…Liver, vWAT, and body weight, solid food, and liquid intake, as well as energy consumption of female Sprague‐Dawley rats supplemented chronically with liquid fructose and glucose, have been reported previously . In brief, both sugar‐supplemented rats increased their total energy intake by 55%.…”

Section: Resultssupporting

confidence: 64%

“…Considering that one rat month is approximately equivalent to three human years, this supplementation period is roughly equivalent to 15–20 years of human life. Using this experimental model, we have previously shown that, despite an increase in daily calorie intake of more than 50% with respect to control animals, liver homeostatic mechanisms reverts the liver fat deposition previously observed in fructose‐supplemented rats over shorter periods of time, probably by a specific activation of the inositol requiring enzyme 1 branch of the unfolded protein response . However, rats supplemented with fructose for 7 months clearly showed extra‐hepatic impaired insulin signaling and glucose intolerance, two metabolic alterations already detected in rats supplemented with fructose for 2 months .…”

Section: Introductionmentioning

confidence: 71%

“…Besides fructose‐related hyperleptinemia, we have previously reported that only glucose‐supplemented rats show an increased concentration of plasma adiponectin (see Table S2, Supporting Information). Although the vWAT expression of leptin and adiponectin genes was not significantly modified by simple‐sugar supplementation ( Figure A), the plasma leptin:adiponectin ratio, which has been directly correlated with insulin resistance in humans, was significantly increased (×1.8 vs control values; Figure B) only in fructose‐supplemented rats.…”

Section: Resultsmentioning

confidence: 99%

“…Different protein extracts (20–30 μg) from tissues samples were subjected to SDS‐polyacrylamide gel electrophoresis. Proteins were then transferred to Immobilon polyvinylidene difluoride transfer membranes (Millipore, Billerica, MA, USA), blocked for 1 h at room temperature with 5% nonfat milk solution in Tris‐buffered saline with 0.1% Tween‐20, and incubated as described previously . Detection was performed using the ECL chemiluminescence kit for HRP (Pierce ECL Western Blotting Substrate, Rockford, IL, USA).…”

Section: Methodsmentioning

confidence: 99%

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Chronic Liquid Fructose, but not Glucose, Supplementation Selectively Induces Visceral Adipose Tissue Leptin Resistance and Hypertrophy in Female Sprague‐Dawley Rats

Sangüesa

Roglans

Montañés

et al. 2018

Molecular Nutrition Food Res

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Scope The effect of chronic supplementation with simple‐sugar solutions on leptin signaling in liver, hypothalamus, and visceral white adipose tissue (vWAT) is studied, which is designed to mimic the temporal pattern of consumption by humans. Methods and Results Solutions of fructose or glucose are isocalorically supplemented (7 months) in female Sprague‐Dawley rats consuming ad libitum rodent chow. After sacrifice, plasma and tissue samples (liver, hypothalamus, and vWAT) are collected. Zoometric parameters, plasma analytes, and the tissue expression and activity of markers of leptin signaling are determined by biochemical and molecular biological methods. The two sugars cause different types of adiposopathy. Both sugars induce increases in plasma nonesterified fatty acids, and leptin resistance in the liver and the hypothalamus. Only fructose‐supplemented rats show hyperleptinemia, and increased body weight due to a hypertrophy of vWAT, with no signs of leptin‐mediated lipolysis. Glucose‐supplemented rats show no significant changes in these parameters but present elevated plasma adiponectin concentrations, lipolysis, and inflammatory markers in vWAT, indicating a shift to a nonexpandable adipose tissue phenotype. Conclusion Chronic consumption of fructose places a greater burden on metabolic homeostasis than equivalent consumption of glucose, inducing hyperleptinemia, generalized leptin resistance, and increased body weight due to expanded, hypertrophic vWAT.

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Section: Resultssupporting

confidence: 64%

Section: Introductionmentioning

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Chronic Liquid Fructose, but not Glucose, Supplementation Selectively Induces Visceral Adipose Tissue Leptin Resistance and Hypertrophy in Female Sprague‐Dawley Rats

Sangüesa

Roglans

Montañés

et al. 2018

Molecular Nutrition Food Res

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“…; Alwahsh and Gebhardt ), it was also shown that chronic supplementation with fructose (10%, w/v) for 7 months did not induce hepatic steatosis and inflammation in female Sprague–Dawley rats (Sangüesa et al. ).…”

Section: Discussionmentioning

confidence: 94%

The long‐term protective effects of neonatal administration of curcumin against nonalcoholic steatohepatitis in high‐fructose‐fed adolescent rats

et al. 2019

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There is an increased prevalence of nonalcoholic steatohepatitis ( NASH ) in adolescents. The suckling period is developmentally plastic, affecting later health outcomes. We investigated whether neonatal administration of curcumin would provide protection against the development of NASH later in adolescence in rats fed a high‐fructose diet. From postnatal day ( PN ) 6 to PN 21, the pups ( N = 128) were allocated to four groups and orally gavaged daily with either 0.5% dimethyl sulfoxide solution (vehicle control), curcumin (500 mg·kg −1 ), fructose (20%, w/v) or curcumin and fructose combined. All the pups were weaned and half the rats in each group had tap water, whereas the other received fructose (20%) as their drinking fluid ad libitum for 6 weeks. The rats’ liver NASH scores, lipid content, and RNA gene expression ratios of AMPK α and TNF α were determined. Hepatic lipid content was similar across the treatment groups in the males ( P > 0.05, ANOVA ). In the females, the hepatic lipid content in the treatment groups ranged from 2.7 to 4.3%. The livers of male and female rats that had fructose either as neonates and/or postweaning had significantly marked inflammation ( P = 0.0112, Kruskal–Wallis) and fibrosis ( P < 0.0001, ANOVA ) which were attenuated by curcumin. The hepatic gene expression ratios for AMPK α in both sexes were significantly downregulated ( P < 0.0001, ANOVA ), whereas the expression ratios of TNF α were significantly upregulated ( P < 0.0001) in rats fed a high‐fructose diet pre and/or postweaning compared to the other groups. Neonatal curcumin administration is a potential natural pharmacological candidate for the prevention of NASH .

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ChREBP‐driven DNL and PNPLA3 Expression Induced by Liquid Fructose are Essential in the Production of Fatty Liver and Hypertriglyceridemia in a High‐Fat Diet‐Fed Rat Model

Velázquez

Bentanachs

Sala‐Vila

et al. 2022

Molecular Nutrition Food Res

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The aim of this study is to delineate the contribution of dietary saturated fatty acids (FA) versus liquid fructose to fatty liver and hypertriglyceridemia. Methods and Results: Three groups of female rats are maintained for 3 months in standard chow (CT); High-fat diet (46.9% of fat-derived calories, rich in palmitic and stearic FA, HFD); and HFD with 10% w/v fructose in drinking water (HFHFr). Zoometric parameters, plasma biochemistry, and liver Oil-Red O (ORO) staining, lipidomics, and expression of proteins involved in FA metabolism are analyzed. Both diets increase ingested calories without modifying body weight. Only the HFHFr diet increases liver triglycerides (x11.0), with hypertriglyceridemia (x1.7) and reduces FA 𝜷-oxidation (x0.7), and increases liver FA markers of DNL (de novo lipogenesis). Whereas HFD livers show a high content of ceramides, HFHFr samples show unchanged ceramides, and an increase in diacylglycerols. Only the HFHFr diet leads to a marked increase in the expression of enzymes involved in DNL and triglyceride metabolism, such as carbohydrate response element binding protein 𝜷 (ChREBP𝜷, x3.2), a transcription factor that regulates DNL, and patatin-like phospholipase domain-containing 3 (PNPLA3, x2.6), a lipase that mobilizes stored triglycerides for VLDL secretion. Conclusion: The addition of liquid-fructose to dietary FA is determinant in liver steatosis and hypertriglyceridemia production, through increased DNL and PNPLA3 expression, and reduced FA catabolism.

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Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague–Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression

Cited by 12 publications

References 55 publications

Chronic Liquid Fructose, but not Glucose, Supplementation Selectively Induces Visceral Adipose Tissue Leptin Resistance and Hypertrophy in Female Sprague‐Dawley Rats

Chronic Liquid Fructose, but not Glucose, Supplementation Selectively Induces Visceral Adipose Tissue Leptin Resistance and Hypertrophy in Female Sprague‐Dawley Rats

The long‐term protective effects of neonatal administration of curcumin against nonalcoholic steatohepatitis in high‐fructose‐fed adolescent rats

ChREBP‐driven DNL and PNPLA3 Expression Induced by Liquid Fructose are Essential in the Production of Fatty Liver and Hypertriglyceridemia in a High‐Fat Diet‐Fed Rat Model

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