Fructose-induced Dyslipidemia Research Articles

Investigations of Ameliorative Potentials Extract of P. pellucida on Salt - Fructose Induced Dyslipidemia in Wistar Rats

Investigations of Ameliorative Potentials Extract of P. pellucida on Salt - Fructose Induced Dyslipidemia in Wistar Rats

Dexamethasone Promotes the Risk of Cardiovascular Disease in High Fructose-exposed Wistar Rats

Background: Dyslipidemia constitutes a serious public health concern globally. It has been established that excessive fructose intake results in dyslipidemia; however, whether dexamethasone aggravates or alleviates fructose-induced dyslipidemia is unknown. Thus, we examined the effects of dexamethasone on dyslipidemia and hyperuricemia in high fructose-taking Wister rats. Materials and Methods: Twenty male Wister rats were randomly grouped as control (distilled water), fructose (10% fructose w/v), dexamethasone (0.2 mg/kg, PO) and fructose+dexamethasone. After a 21-day exposure, the serum and heart samples were harvested, processed and analyzed for biochemical assays. Results: Our findings reveal that exposure of rats to high fructose significantly increased blood glucose, elevated serum triglycerides and uric acid, activity of xanthine oxidase, and lowered high density lipoprotein cholesterol (HDL) level. However, dexamethasone administration had no significant effect on the blood glucose and did not alter the serum levels of triglycerides, uric acid and xanthine oxidase. Meanwhile, both fructose and dexamethasone treatments independently elevated the serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL) and malondialdehyde. Further, the fructose treatment elevated the TG/HDL ratio, while both fructose and dexamethasone treatments individually and synergistically elevated TC/HDL ratio. Our study also showed that co-administration of fructose and dexamethasone aggravated the elevated serum levels of TC and LDL, while it impaired the enzymatic antioxidant systems. Conclusion: Dexamethasone, though slightly reduced fructose-induced hyperglycemia, impaired the antioxidant enzymes and escalated dyslipidemia during fructose intake. Hence, our study suggests that dexamethasone administration may increase the risk of CVD in animals with excessive intake of fructose.

Acute toxicity and anti-dyslipidemic activity of Arogyavardhini compound in fructose-induced dyslipidemia in albino rats

Metabolic syndrome is a co-occurrence of obesity, insulin resistance, hypertension, and dyslipidemia caused by improper diet and lifestyle. Arogyavardhini compound (AVC) contains an equal quantity of Arogyavardhini rasa and Lasuna powder. In clinical practice, Arogyavardhini Rasa is well known for its antidyslipidemic and weight lowering effect. Therefore, the present experimental study was designed to evaluate the safety of AVC on acute administration and anti-dyslipidemic activity in albino rats. An acute oral toxicity study for AVC was carried out by following OECD 425 guidelines. The anti-dyslipidemic activity was carried out against fructose-induced dyslipidemia in albino rats. No mortality and toxicity were observed and gross behaviours of all the albino rats were found normal during the experimental period of 14 days in the acute toxicity study. Fructose significantly increased blood sugar, triglycerides, SGPT, and alkaline phosphatase levels in albino rats in comparison to the control group. AVC treated group produced a decrease in serum triglyceride, transaminases, and alkaline phosphatase, which suggest that the drug has potential as anti-dyslipidemic and may be protective for degenerative changes produced by fructose in the liver, kidney, and heart of albino rats. From the present study it is concluded that AVC is safe up to an oral dose of 2000 mg/kg in albino rats and has exhibited a protective role in fructose-induced dyslipidemia in albino rats, hence may be useful in metabolic syndrome.

Diets with low n-6:n-3 PUFA ratio protects rats from fructose-induced dyslipidemia and associated hepatic changes: Comparison between 18:3 n-3 and long-chain n-3 PUFA

In the present study, we investigated the impact of substituting alpha-linolenic acid (ALA) or long-chain n-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) for linoleic acid and hence decreasing n-6:n-3 PUFA ratio on high-fructose diet-induced hypertriglyceridemia and associated hepatic changes. Weanling male Wistar rats were divided into four groups and fed with starch-diet (n-6:n-3 PUFA ratio 215:1) and high-fructose diets with different n-6:n-3 PUFA ratio (215:1, 2:1 with ALA and 5:1 with long-chain n-3 PUFA) for twenty-four weeks. Substitution of linoleic acid with ALA (n-6:n-3 PUFA ratio of 2) or long-chain n-3 PUFA (n-6:n-3 PUFA ratio of 5) protected the rats from fructose-induced dyslipidemia, hepatic oxidative stress and corrected lipogenic and proinflammatory gene expression. Both ALA and long-chain n-3 PUFA supplementation also reversed the fructose-induced upregulation of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene, which is involved in the generation of active glucocorticoids in tissues. Although both ALA and LC n-3 PUFA prevented fructose-induced dyslipidemia to a similar extent, compared to ALA, LC n-3 PUFA is more effective in preventing hepatic oxidative stress and inflammation.

Dietary fructose and dyslipidemia: new mechanisms involving apolipoprotein CIII.

Chronic consumption of fructose and fructose-containing sugars leads to dyslipidemia. Apolipoprotein (apo) CIII is strongly associated with elevated levels of triglycerides and cardiovascular disease risk. We reviewed the effects of fructose consumption on apoCIII levels and the role of apoCIII in fructose-induced dyslipidemia. Consumption of fructose increases circulating apoCIII levels compared with glucose. The more marked effects of fructose compared with glucose on apoCIII concentrations may involve the failure of fructose consumption to stimulate insulin secretion. The increase in apoCIII levels after fructose consumption correlates with increased postprandial serum triglyceride. Further, RNA interference of apoCIII prevents fructose-induced dyslipidemia in nonhuman primates. Increases in postprandial apoCIII after fructose, but not glucose consumption, are positively associated with elevated triglycerides in large triglyceride-rich lipoproteins and increased small dense LDL levels. ApoCIII might be causal in the lipid dysregulation observed after consumption of fructose and fructose-containing sugars. Decreased consumption of fructose and fructose-containing sugars could be an effective strategy for reducing circulating apoCIII and subsequently lowering triglyceride levels.

297-LB: Dietary Fructose Increases Plasma Angiopoietin-Like Protein-3 Concentrations in Rhesus Macaques: Prevention with Fish Oil Supplementation

Homozygous loss-of-function ANGPTL3variants are associated with familial combined hypolipidemia, suggesting the dual LPL/EL inhibitor is a promising target for treating atherogenic dyslipidemia. However, nothing is known regarding the dietary regulation of ANGPTL3, including effects of dietary sugar or n-3 fatty acids. We investigated plasma ANGPTL3 concentrations in a rhesus macaque model of high sugar diet-induced dyslipidemia. Animals provided fructose beverages (300 kcal/d) rapidly gain weight (∼10%) and develop insulin resistance and fasting hypertriglyceridemia within 1 month. Fasting plasma ANGPTL3 concentrations increased by 30-40% with fructose consumption after 1 and 3 months (mean±SD in ng/ml; baseline, 60.6±17.4; 1 month, 83.1±25.3; 3 months, 76.9±23.2; both p<0.001 vs. baseline, n=59). Fish oil supplementation (4 g/d) prevents fructose-induced dyslipidemia and completely prevented the increases of ANGPTL3 (-3% vs. +33% over 6 months, p<0.05). Regression modeling to identify lipid/lipoprotein parameters (TG, TC, HDL-C, LDL-C, VLDL-C, APOA1, APOB, APOC3, APOE) explaining variation in ANGPTL3 levels indicated strong correlations with APOC3 at baseline (p=0.002), and APOC3 and APOE after 3 months of fructose (both p<0.05). Regression modeling also examined whether changes (?) of APOC3, APOE, and ANGPTL3 predict ?TG, explaining 41% of variation after 1 month. (R2=0.41, p<0.001). ?APOC3 (B=0.588, p<0.001) and ?ANGPTL3 (B=0.292, p<0.05) were significant predictors in the model. After 3 months, modeling explained 36% of ∆TG (R2=0.36, p<0.001), with all variables contributing significantly (?APOC3, B=0.616, p<0.001; ?ANGPTL3, B=0.245, p<0.05; ?APOE, B= -0.281, p<0.05). Modeling predicted variation of ∆TG before and during fructose consumption (R2=0.294, p=0.033 at baseline; R2=0.438, p<0.001 at 3 months). In summary, these are the first findings reporting effects of diet composition (sugar and n-3 FAs) on circulating ANGPTL3. Disclosure A. Butler: None. J.L. Graham: Research Support; Self; Arrowhead Research, Bristol-Myers Squibb Company, Magnamosis Inc. K.L. Stanhope: None. P.J. Havel: Research Support; Self; Arrowhead Research, Bristol-Myers Squibb Company, Magnamosis Inc. Funding National Institutes of Health

Liquid fructose in pregnancy exacerbates fructose-induced dyslipidemia in adult female offspring

Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and related events. Nevertheless, consumption of beverages sweetened with fructose is not regulated in gestation. Previously, we found that maternal fructose intake produces in the progeny, when fetuses, impaired leptin signaling and hepatic steatosis and then impaired insulin signaling and hypoadiponectinemia in adult male rats. Interestingly, adult females from fructose-fed mothers did not exhibit any of these disturbances. However, we think that, actually, these animals keep a programmed phenotype hidden. Fed 240-day-old female progeny from control, fructose- and glucose-fed mothers were subjected for 3weeks to a fructose supplementation period (10% wt/vol in drinking water). Fructose intake provoked elevations in insulinemia and adiponectinemia in the female progeny independently of their maternal diet. In accordance, the hepatic mRNA levels of several insulin-responsive genes were similarly affected in the progeny after fructose intake. Interestingly, adult progeny of fructose-fed mothers displayed, in response to the fructose feeding, augmented plasma triglyceride and NEFA levels and hepatic steatosis versus the other two groups. In agreement, the expression and activity for carbohydrate response element binding protein (ChREBP), a lipogenic transcription factor, were higher after the fructose period in female descendants from fructose-fed mothers than in the other groups. Furthermore, liver fructokinase expression that has been indicated as one of those responsible for the deleterious effects of fructose ingestion was preferentially augmented in that group. Maternal fructose intake does influence the adult female offspring's response to liquid fructose and so exacerbates fructose-induced dyslipidemia and hepatic steatosis.

GLP-1 receptor agonism ameliorates hepatic VLDL overproduction and de novo lipogenesis in insulin resistance.

Background/objectivesFasting dyslipidemia is commonly observed in insulin resistant states and mechanistically linked to hepatic overproduction of very low density lipoprotein (VLDL). Recently, the incretin hormone glucagon-like peptide-1 (GLP-1) has been implicated in ameliorating dyslipidemia associated with insulin resistance and reducing hepatic lipid stores. Given that hepatic VLDL production is a key determinant of circulating lipid levels, we investigated the role of both peripheral and central GLP-1 receptor (GLP-1R) agonism in regulation of VLDL production.MethodsThe fructose-fed Syrian golden hamster was employed as a model of diet-induced insulin resistance and VLDL overproduction. Hamsters were treated with the GLP-1R agonist exendin-4 by intraperitoneal (ip) injection for peripheral studies or by intracerebroventricular (ICV) administration into the 3rd ventricle for central studies. Peripheral studies were repeated in vagotomised hamsters.ResultsShort term (7–10 day) peripheral exendin-4 enhanced satiety and also prevented fructose-induced fasting dyslipidemia and hyperinsulinemia. These changes were accompanied by decreased fasting plasma glucose levels, reduced hepatic lipid content and decreased levels of VLDL-TG and -apoB100 in plasma. The observed changes in fasting dyslipidemia could be partially explained by reduced respiratory exchange ratio (RER) thereby indicating a switch in energy utilization from carbohydrate to lipid. Additionally, exendin-4 reduced mRNA markers associated with hepatic de novo lipogenesis and inflammation. Despite these observations, GLP-1R activity could not be detected in primary hamster hepatocytes, thus leading to the investigation of a potential brain–liver axis functioning to regulate lipid metabolism. Short term (4 day) central administration of exendin-4 decreased body weight and food consumption and further prevented fructose-induced hypertriglyceridemia. Additionally, the peripheral lipid-lowering effects of exendin-4 were negated in vagotomised hamsters implicating the involvement of parasympathetic signaling.ConclusionExendin-4 prevents fructose-induced dyslipidemia and hepatic VLDL overproduction in insulin resistance through an indirect mechanism involving altered energy utilization, decreased hepatic lipid synthesis and also requires an intact parasympathetic signaling pathway.

Exercise Prevents Fructose‐Induced Hypertriglyceridemia in Healthy Young Males

A high fructose intake increases plasma triglyceride (TG) concentrations in sedentary humans, but the effects of exercise are not known. This study was designed to evaluate the effects of a weight‐maintenance, high fructose diet with or without moderate physical activity.8 healthy males were studied on three occasions, after 4 days on a) a diet low in fructose and no exercise (Ctrl), b) a diet with 30% fructose and no exercise (Fru), or c) a diet with 30% fructose and moderate exercise (60 min cycling at 125 W; FruEx). In each condition, energy intake was adjusted to energy requirements (resting energy requirements times 1.5 for Ctrl and Fru, times 1.7 for FruEx). On each occasion, substrate oxidation was measured by calorimetry and de novo lipogenesis was assessed from VLDL 13C‐palmitate after 13C‐fructose loading.Fru significantly increased TG by 18 ± 12%, and VLDL 13C‐palmitate by 333 ± 231% (both p<0.05 vs Ctrl). FruEx blunted the increase in TG (−6 ± 9%), VLDL 13C‐palmitate (−55 ± 28%), and increased lipid oxidation, non‐esterified fatty acid and beta‐hydroxybutyric acid concentrations by 122 ± 45%, 34 ± 16%, and 48 ± 17 % (all p<0.05 vs Ctrl).We conclude that a moderate exercise prevents fructose‐induced dyslipidemia in healthy males, independently of energy balance. This work was supported by the Swiss National Science Foundation

Supplementation of Bitter Melon to Rats Fed a High-Fructose Diet During Gestation and Lactation Ameliorates Fructose-Induced Dyslipidemia and Hepatic Oxidative Stress in Male Offspring

This study examined the impact of maternal high-fructose intake and if metabolic control in the offspring could benefit from supplementing bioactive food components such as bitter melon (BM) to the maternal diet. In Expt. 1, virgin female rats received control (C), high-fructose (F; 60%), or BM-supplemented fructose (FBM; 1%) diet before conception until d 21 of lactation. Weaned male offspring were fed the C diet for 11 wk, forming C/C, F/C, and FBM/C groups. The F/C group had elevated serum insulin, TG, and FFA concentrations and hepatic lipid alterations compared with the C/C and FBM/C groups (P < 0.05). The 2 latter groups did not differ. Expt. 2 had similar dam treatment groups, but offspring were weaned to the C or F diet, forming C/C, C/F, F/F, and FBM/F groups, and the dietary treatment was extended to 20 wk. The hepatic levels of stearyl-CoA desaturase and microsomal TG transfer protein mRNA were lower, but that of PPARγ coactivator 1-α and fibroblast growth factor 21 mRNA and fatty acid binding protein 1 protein were higher in the FBM/F group compared with the C/F and F/F groups (P < 0.05), indicating that maternal BM supplementation may reduce lipogenesis and promote lipid oxidation in offspring. The FBM/F group had significantly higher activities of liver glutathione peroxidase, superoxide dismutase, and catalase than the F/F group. The results indicate that supplementing BM to dams could offset the adverse effects of maternal high-fructose intake on lipid metabolism and antioxidant status in adult offspring.

Fructose Consumption: Considerations for Future Research on Its Effects on Adipose Distribution, Lipid Metabolism, and Insulin Sensitivity in Humans

Results from a recent study investigating the metabolic effects of consuming fructose-sweetened beverages at 25% of energy requirements for 10 wk demonstrate that a high-fructose diet induces dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity. The purpose of this review is to present aspects of the study design which may be critical for assessment of the metabolic effects of sugar consumption. Collection of postprandial blood samples is required to document the full effects of fructose on lipid metabolism. Fasting triglyceride (TG) concentrations are an unreliable index of fructose-induced dyslipidemia. Differences in the short-term (24-h) and long-term (>2 wk) effects of fructose consumption on TG and apolipoprotein-B demonstrate that acute effects can differ substantially from those occurring after sustained fructose exposure. Investigating the effects of fructose when consumed ad libitum compared with energy-balanced diets suggest that additive effects of fructose-induced de novo lipogenesis and positive energy balance may contribute to dyslipidemia and decreased insulin sensitivity. Increases of intra-abdominal fat observed in subjects consuming fructose, but not glucose, for 10 wk indicate that the 2 sugars have differential effects on regional adipose deposition. However, the increase of fasting glucose, insulin, and homeostasis model assessment-insulin resistance at 2 wk and the lack of increase of 24-h systemic FFA concentrations suggest that fructose decreases insulin sensitivity independently of visceral adiposity and FFA. The lower postprandial glucose and insulin excursions in subjects consuming fructose and increased excursions in those consuming glucose do not support a relationship between dietary glycemic index and the development of dyslipidemia, decreased insulin sensitivity, or increased visceral adiposity.

Fructose Induced Leptin Dysfunction and Improvement by Quercetin and Rutin in Rats

To investigate the dysfunction of leptin underlying insulin resistance syndrome in fructose-fed rats and improvement by lowing uric acid with natural products quercetin and rutin. Rats were fed with fructose solution for 8 weeks. At week 4, animals received quercetin and rutin, as well as allopurinol. Serum uric acid and insulin levels were measured before and after drug treatment. Leptin levels in serum and hypothalamus, leptin secretion from adipose tissue were used to evaluate the responses of leptin to hyperuricemia and hyperinsulinemia in rats with insulin resistance syndrome. Triglyceride (TG), high dense lipid (HDL) and low dense lipid (LDL) in serum were examined to evaluate dyslipidemia in fructose-fed rats. Fructose consumption significantly increased serum uric acid, insulin and leptin levels in rats, and induced a significant increase of leptin secretion by upregulating ob gene expression in adipose tissue. Quercetin and rutin, as well as allopurinol reduced hyperleptinemia and inhibited leptin secretion from adipose tissue. Moreover, fructose-fed rats exhibited leptin level increase in hypothalamus accompanying dyslipidemia. Quercetin, rutin and allopurinol attenuated fructose-induced dyslipidemia in rats, but failed to improve leptin insufficiency in hypothalamus. These results indicated that fructose consumption might cause hyperleptinemia and leptin insufficiency in the brain, which might be indirectly mediated by hyperinsulinemia and hypertriglyceridemia in rats. Hopouricemic agents quercetin, rutin and allopurinol improved hyperinsulinemia and dyslipidemia, and subsequently regulated leptin dysfunction in fructose-fed rats. This study provided direct evidence that hyperuricemia was associated with hyperleptinemia during fructose consumption, and another pharmacological explanation for lowing uric acid agents to prevent hyperuricemia and leptin dysfunctions in fructose-induced insulin resistance syndrome in rats.