Role of high-fructose diet in experimental induction of nonalcoholic steatohepatitis in rats

The renin-angiotensin system (RAS) has been implicated in the cardiovascular complications of diabetes. We showed that a high-fructose diet increases blood pressure and plasma angiotensin and impairs glucose tolerance. We investigated the role of angiotensin AT1a receptors in the development of fructose-induced cardiovascular and metabolic dysfunction. Male angiotensin AT1a knockout (AT1aKO) and wild-type (AT1aWT) mice with arterial telemetric catheters were fed a standard diet or one containing 60% fructose. Fructose increased mean arterial pressure (MAP) in AT1aWT but only during the dark phase (8% increase). In AT1aKO mice, fructose unexpectedly decreased MAP, during both light and dark periods (24 and 13% decrease, respectively). Analytical methods were used to measure systolic arterial pressure (SAP) and pulse interval (PI) variability in time and frequency domains. In fructose-fed AT1aWT mice, there was an increase in SAP variance and its low-frequency (LF) domain (11 ± 3 vs. 23 ± 4 mmHg2, variance, and 7 ± 2 vs. 17 ± 3 mmHg2, LF, control vs. fructose, P < 0.004). There were no changes in SAP variance in AT1aKO mice. Depressor responses to α1-adrenergic blockade were augmented in fructose-fed AT1a WT compared with AT1aKO mice. Fructose inhibited glucose tolerance with a greater effect in AT1aWT mice. Fructose increased plasma cholesterol in both groups ( P < 0.01) and reduced ANG II in AT1aKO mice. Results document prominent interactions between genetics and diet with data showing that in the absence of angiotensin AT1a receptors, a fructose diet decreased blood pressure.

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Effect of high-fructose diet-induced metabolic syndrome on the pituitary-gonadal axis from adolescence through adulthood in male albino rats and the possible protective role of ginger extract. A biochemical, histological and immunohistochemical study

Folia Morphologica ◽

10.5603/fm.a2019.0139 ◽

2020 ◽

Vol 79 (4) ◽

pp. 690-708

Author(s):

A. E. El-Mehi ◽

M. A. Faried

Keyword(s):

Metabolic Syndrome ◽

Immunohistochemical Study ◽

Protective Role ◽

Albino Rats ◽

Ginger Extract ◽

High Fructose Diet ◽

High Fructose

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Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome

AJP Renal Physiology ◽

10.1152/ajprenal.00454.2007 ◽

2008 ◽

Vol 294 (4) ◽

pp. F710-F718 ◽

Cited By ~ 103

Author(s):

Laura G. Sánchez-Lozada ◽

Edilia Tapia ◽

Pablo Bautista-García ◽

Virgilia Soto ◽

Carmen Ávila-Casado ◽

...

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Oxidase Inhibitor ◽

Normal Diet ◽

Xanthine Oxidase Inhibitor ◽

Morphological Alterations ◽

Renal Vasoconstriction ◽

High Fructose Diet ◽

High Fructose

Increased fructose consumption is associated with hyperuricemia, metabolic syndrome, and renal damage. This study evaluated whether febuxostat (Fx), an investigational nonpurine, and selective xanthine oxidase inhibitor, could alleviate the features of metabolic syndrome as well as the renal hemodynamic alterations and afferent arteriolopathy induced by a high-fructose diet in rats. Two groups of rats were fed a high-fructose diet (60% fructose) for 8 wk, and two groups received a normal diet. For each diet, one group was treated with Fx (5–6 mg·kg−1·day−1 in the drinking water) during the last 4 wk (i.e., after the onset of metabolic syndrome), and the other received no treatment (placebo; P). Body weight was measured daily. Systolic blood pressure and fasting plasma uric acid (UA), insulin, and triglycerides were measured at baseline and at 4 and 8 wk. Renal hemodynamics and histomorphology were evaluated at the end of the study. A high-fructose diet was associated with hyperuricemia, hypertension, as well as increased plasma triglycerides and insulin. Compared with fructose+P, fructose+Fx rats showed significantly lowered blood pressure, UA, triglycerides, and insulin ( P < 0.05 for all comparisons). Moreover, fructose+Fx rats had significantly reduced glomerular pressure, renal vasoconstriction, and afferent arteriolar area relative to fructose+P rats. Fx treatment in rats on a normal diet had no significant effects. In conclusion, normalization of plasma UA with Fx in rats with metabolic syndrome alleviated both metabolic and glomerular hemodynamic and morphological alterations. These results provide further evidence for a pathogenic role of hyperuricemia in fructose-mediated metabolic syndrome.

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Peculiarities of Metabolism of Rats with Fructose-induced Insulin Resistance Against the Background of Congenital and Acquired Iodine Deficiency

Galician Medical Journal ◽

10.21802/gmj.2019.4.13 ◽

2019 ◽

Vol 26 (4) ◽

Author(s):

Vasyl Stetseviat

Keyword(s):

Insulin Resistance ◽

Carbohydrate Metabolism ◽

Iodine Deficiency ◽

Total Cholesterol Level ◽

Glycosylated Hemoglobin ◽

High Density Lipoproteins ◽

High Fructose Diet ◽

High Fructose ◽

Increased Risk

Animals following a high-fructose diet during eight weeks, have experienced changes in metabolism and the signs of insulin resistance have developed. Under such conditions, moderate hyperglycemia, hyperinsulinemia, hyperuricemia, an increase of the level of glycosylated hemoglobin in whole blood were observed. The significant role of the HOMA-IR index, as an early marker of carbohydrate metabolism disorders at the stage of pre-diabetes, has been confirmed. In experimental animals against the background of the high-fructose diet, the changes in the lipid spectrum of the blood were revealed: an increase of the total cholesterol level, low-density lipoproteins, triglycerides against the background of a high-density lipoproteins decrease. These disorders and a significant increase of the atherogenicity reflect the development of secondary dyslipidemia. In this case, the disorders of carbohydrate metabolism were combined with the degree of dyslipidemia. Males were found to have at increased risk of development the insulin resistance and comorbid pathology. Iodine deficiency, especially of congenital nature, is an aggravating factor of metabolic disorders. The obtained data can serve as a basis for extend of preventive measures and identification of the priority treatment schemes for type 2 diabetes mellitus in residents of endemic regions.

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Role of AMPD2 in impaired glucose tolerance induced by high fructose diet

Molecular Genetics and Metabolism Reports ◽

10.1016/j.ymgmr.2017.07.006 ◽

2017 ◽

Vol 13 ◽

pp. 23-29 ◽

Cited By ~ 7

Author(s):

Athanasius Wrin Hudoyo ◽

Tetsuaki Hirase ◽

Andreas Tandelillin ◽

Masahiko Honda ◽

Manabu Shirai ◽

...

Keyword(s):

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

High Fructose Diet ◽

High Fructose

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Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a high fructose diet

Biological Research ◽

10.1186/s40659-015-0045-4 ◽

2015 ◽

Vol 48 (1) ◽

Cited By ~ 8

Author(s):

Romina Hernández-Salinas ◽

Valerie Decap ◽

Alberto Leguina ◽

Patricio Cáceres ◽

Druso Perez ◽

...

Keyword(s):

Wine Grape ◽

High Fructose Diet ◽

High Fructose

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Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00076.2017 ◽

2017 ◽

Vol 313 (2) ◽

pp. E203-E212 ◽

Cited By ~ 23

Author(s):

Natsasi Chukijrungroat ◽

Tanaporn Khamphaya ◽

Jittima Weerachayaphorn ◽

Thaweesak Songserm ◽

Vitoon Saengsirisuwan

Keyword(s):

Sex Differences ◽

Protein Expression ◽

Fatty Liver ◽

Hepatic Steatosis ◽

Male Rats ◽

High Fat ◽

High Fructose Diet ◽

Ovx Rats ◽

High Fructose

The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFD-fed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFD-induced hepatic steatosis.

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