Ovariectomy, but not orchiectomy, exacerbates metabolic syndrome after maternal high-fructose intake in adult offspring

Public health issues have been raised regarding fructose toxicity and its serious metabolic disorders. Deleterious effects of high fructose intake on insulin sensitivity, body weight, lipid homeostasis have been identified. The new millennium has witnessed the emergence of a modern epidemic, the metabolic syndrome (MS), in approximately 25% of the world’s adult population. The current study aimed to investigate the effect of the TNF-α antagonist infliximab on fructose-induced MS in rats. Rats were administered fructose (10%) in drinking water for 12 weeks to induce the experimental MS model. infliximab (5 mg/kg) was injected once weekly intraperitoneally starting on the 13th week for 4 weeks. Increase in body weight, blood glucose level, serum triglycerides (TGs), adiponectin level and blood pressure were present in MS rats. They also prompted increases in serum of leptin, TNF-α, and malondialdehyde (MDA) levels. Treatment with infliximab did not affect body weight, hyperglycemia or hypertension, but decreased serum TGs and increased serum HDL-c levels. Infliximab also decreased adiponectin levels. Surprisingly, infliximab increased MDA above its value in the MS group. These results reflect the fact that infliximab affects the manifestations of MS in rats. Though infliximab reduced TGs, increased HDL-c levels, reversed adiponectin resistance occurred by fructose, the drug failed to combat MS-mediated hyperglycemia, hypertension, and elevated MDA above the insult.

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Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/3419479 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8

Author(s):

Aburrahman Gun ◽

Mehmet Kaya Ozer ◽

Sedat Bilgic ◽

Nevin Kocaman ◽

Gonca Ozan

Keyword(s):

Metabolic Syndrome ◽

Caffeic Acid ◽

Vascular Function ◽

Vascular Dysfunction ◽

Caffeic Acid Phenethyl Ester ◽

High Fructose Corn Syrup ◽

Corn Syrup ◽

Beneficial Effects ◽

Fructose Intake ◽

High Fructose

Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE) has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS). HFCS (6 weeks, 30% fed with drinking water) caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks) effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS) production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

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A causal role for uric acid in fructose-induced metabolic syndrome

AJP Renal Physiology ◽

10.1152/ajprenal.00140.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. F625-F631 ◽

Cited By ~ 616

Author(s):

Takahiko Nakagawa ◽

Hanbo Hu ◽

Sergey Zharikov ◽

Katherine R. Tuttle ◽

Robert A. Short ◽

...

Keyword(s):

Nitric Oxide ◽

Metabolic Syndrome ◽

Uric Acid ◽

Endothelial Function ◽

Control Diet ◽

Oxidase Inhibitor ◽

Xanthine Oxidase Inhibitor ◽

Fructose Intake ◽

High Fructose ◽

Aortic Artery

The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid.

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Targeting on Gut Microbiota-Derived Metabolite Trimethylamine to Protect Adult Male Rat Offspring against Hypertension Programmed by Combined Maternal High-Fructose Intake and Dioxin Exposure

International Journal of Molecular Sciences ◽

10.3390/ijms21155488 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5488 ◽

Cited By ~ 2

Author(s):

Chien-Ning Hsu ◽

Julie Y. H. Chan ◽

Hong-Ren Yu ◽

Wei-Chia Lee ◽

Kay L. H. Wu ◽

...

Keyword(s):

Gut Microbiota ◽

Corn Oil ◽

Male Rat ◽

Adult Offspring ◽

Male Adult ◽

High Fructose Diet ◽

Fructose Intake ◽

High Fructose ◽

Pregnancy And Lactation ◽

Dioxin Exposure

Gut microbiota-dependent metabolites, in particular trimethylamine (TMA), are linked to hypertension. Maternal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or consumption of food high in fructose (HFR) can induce hypertension in adult offspring. We examined whether 3,3-maternal dimethyl-1-butanol (DMB, an inhibitor of TMA formation) therapy can protect adult offspring against hypertension arising from combined HFR and TCDD exposure. Pregnant Sprague–Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) throughout pregnancy and lactation. Additionally, the pregnant dams received TCDD (200 ng/kg BW orally) or a corn oil vehicle on days 14 and 21 of gestation, and days 7 and 14 after birth. Some mother rats received 1% DMB in their drinking water throughout pregnancy and lactation. Six groups of male offspring were studied (n = 8 for each group): regular chow (CV), high-fructose diet (HFR), regular diet+TCDD exposure (CT), HFR+TCDD exposure (HRT), high-fructose diet+DMB treatment (HRD), and HFR+TCDD+DMB treatment (HRTD). Our data showed that TCDD exacerbates HFR-induced elevation of blood pressure in male adult offspring, which was prevented by maternal DMB administration. We observed that different maternal insults induced distinct enterotypes in adult offspring. The beneficial effects of DMB are related to alterations of gut microbiota, the increase in nitric oxide (NO) bioavailability, the balance of the renin-angiotensin system, and antagonization of aryl hydrocarbon receptor (AHR) signaling. Our findings cast new light on the role of early intervention targeting of the gut microbiota-dependent metabolite TMA, which may allow us to prevent the development of hypertension programmed by maternal excessive fructose intake and environmental dioxin exposure.

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Copper-Fructose Interactions: A Novel Mechanism in the Pathogenesis of NAFLD

Nutrients ◽

10.3390/nu10111815 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1815 ◽

Cited By ~ 5

Author(s):

Ming Song ◽

Miriam Vos ◽

Craig McClain

Keyword(s):

Metabolic Syndrome ◽

Causal Effect ◽

Critical Role ◽

Metabolic Effects ◽

Nonalcoholic Fatty Liver ◽

Copper Status ◽

Fructose Intake ◽

The Metabolic Syndrome ◽

High Fructose

Compelling epidemiologic data support the critical role of dietary fructose in the epidemic of obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). The metabolic effects of fructose on the development of metabolic syndrome and NAFLD are not completely understood. High fructose intake impairs copper status, and copper-fructose interactions have been well documented in rats. Altered copper-fructose metabolism leads to exacerbated experimental metabolic syndrome and NAFLD. A growing body of evidence has demonstrated that copper levels are low in NAFLD patients. Moreover, hepatic and serum copper levels are inversely correlated with the severity of NAFLD. Thus, high fructose consumption and low copper availability are considered two important risk factors in NAFLD. However, the causal effect of copper-fructose interactions as well as the effects of fructose intake on copper status remain to be evaluated in humans. The aim of this review is to summarize the role of copper-fructose interactions in the pathogenesis of the metabolic syndrome and discuss the potential underlying mechanisms. This review will shed light on the role of copper homeostasis and high fructose intake and point to copper-fructose interactions as novel mechanisms in the fructose induced NAFLD.

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Reversion to regular diet with alternate day fasting can cure grade-I non-alcoholic fatty liver disease (NAFLD) in high-fructose-intake-associated metabolic syndrome

Egyptian Liver Journal ◽

10.1186/s43066-021-00128-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nehal Mohamed Bahgat Gamil ◽

Sahar Mohamed El Agaty ◽

Gehan Khalaf Megahed ◽

Rania Salah Mansour ◽

Marwa Saad Abdel-Latif

Keyword(s):

Metabolic Syndrome ◽

Liver Disease ◽

Fatty Liver Disease ◽

Male Rats ◽

Alcoholic Fatty Liver ◽

Liver Histopathology ◽

Fructose Intake ◽

High Fructose ◽

Alternate Day Fasting ◽

Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem that accompanied the obesity epidemic and is considered as the hepatic component of metabolic syndrome (MetS). Modification of lifestyle of MetS patients remains the focus to reverse and prevent progression of hepatic steatosis to NAFLD and its worsening to severe forms. The present study investigates the possible curability of metabolic syndrome -associated grade-1 NAFLD merely by alternate day fasting with or without reversion to regular diet in adult male rats. The present study was performed on 66 local strain male rats aged (6–10 m.) distributed randomly into C group (n = 12), on regular rat diet; and M group (n = 54) on high fructose- intake. On the 8th week, then rats were subjected to measurement of BW, BMI, WC, FBG, IPGTT, HDL-C, TGs, and liver histopathology, to include MetS rats randomly into four experimental groups for 4 weeks as follows: MS (n = 14); MSRD (n = 12); MSF (n = 13); and MSRDF (n = 12). On the 12th week, all rats were subjected to measurements of BW, BMI, WC, LW, LW/BW, VFW, VFW/BW, FBG, IPGTT, Ins., HOMA-IR, HbA1C, TGs, TC, LDL-C, HDL-C, CRP, Alb., bilirubin, ALT, L-MDA, and liver histopathology. Results On the 8th week, M group developed MerS and grade-I NAFLD with score-4 hepatosteatosis (69%). On the 12th week, MS group had grade-1 NAFLD with score-4 hepatosteatosis (82%) with significantly increased Ins., HOMA-IR, HDL-C, LW, LW/BW, L-MDA, ALT, CRP, and significantly decreased Alb. than C rats. Both MSRD and MSF groups had grade-1 NAFLD with score-3 hepatosteatosis (42%) with significantly decreased Ins., HOMA-IR, TC, LDL-C, LW, LW/BW, L-MDA, ALT, CRP, and significantly increased HDL-C and Alb. than MS group. MSRDF rats showed cure of grade-1 NAFLD and significantly decreased LW than other groups and normalized HOMA-IR, HbA1C TC, LDL-C, ALT, and CRP. Conclusion One month of alternate-day fasting and regular rat diet could cure grade-I NAFLD associated with Mets due to high fructose intake possibly by attenuating metabolic disorders. These two interventions might be recommended in the management of MetS patients with grade 1-NAFLD disease.

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Excess Maternal Fructose Consumption Increases Fetal Loss and Impairs Endometrial Decidualization in Mice

Endocrinology ◽

10.1210/en.2015-1618 ◽

2015 ◽

Vol 157 (2) ◽

pp. 956-968 ◽

Cited By ~ 10

Author(s):

Jessica L. Saben ◽

Zeenat Asghar ◽

Julie S. Rhee ◽

Andrea Drury ◽

Suzanne Scheaffer ◽

...

Keyword(s):

Metabolic Syndrome ◽

Fetal Loss ◽

Reproductive Age ◽

Bone Morphogenetic Protein 2 ◽

Hormone Synthesis ◽

Fructose Intake ◽

Morphogenetic Protein ◽

High Fructose ◽

Previous Decade ◽

Exogenous Progesterone

Abstract The most significant increase in metabolic syndrome over the previous decade occurred in women of reproductive age, which is alarming given that metabolic syndrome is associated with reproductive problems including subfertility and early pregnancy loss. Individuals with metabolic syndrome often consume excess fructose, and several studies have concluded that excess fructose intake contributes to metabolic syndrome development. Here, we examined the effects of increased fructose consumption on pregnancy outcomes in mice. Female mice fed a high-fructose diet (HFrD) for 6 weeks developed glucose intolerance and mild fatty liver but did not develop other prominent features of metabolic syndrome such as weight gain, hyperglycemia, and hyperinsulinemia. Upon mating, HFrD-exposed mice had lower pregnancy rates and smaller litters at midgestation than chow-fed controls. To explain this phenomenon, we performed artificial decidualization experiments and found that HFrD consumption impaired decidualization. This appeared to be due to decreased circulating progesterone as exogenous progesterone administration rescued decidualization. Furthermore, HFrD intake was associated with decreased bone morphogenetic protein 2 expression and signaling, both of which were restored by exogenous progesterone. Finally, expression of forkhead box O1 and superoxide dismutase 2 [Mn] proteins were decreased in the uteri of HFrD-fed mice, suggesting that HFrD consumption promotes a prooxidative environment in the endometrium. In summary, these data suggest that excess fructose consumption impairs murine fertility by decreasing steroid hormone synthesis and promoting an adverse uterine environment.

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Copper-Fructose Interactions: A Novel Mechanism in the Pathogenesis of NAFLD

10.20944/preprints201810.0429.v1 ◽

2018 ◽

Author(s):

Ming Song ◽

Miriam Vos ◽

Craig McClain

Keyword(s):

Metabolic Syndrome ◽

Causal Effect ◽

Critical Role ◽

Metabolic Effects ◽

Nonalcoholic Fatty Liver ◽

Copper Status ◽

Fructose Intake ◽

The Metabolic Syndrome ◽

High Fructose

Compelling epidemiologic data support the critical role of dietary fructose in the epidemic of obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). The metabolic effects of fructose on the development of metabolic syndrome and NAFLD are not completely understood. High fructose intake impairs copper status, and copper-fructose interactions have been well documented in rats. Altered copper-fructose metabolism leads to exacerbated experimental metabolic syndrome and NAFLD. A growing body of evidence has demonstrated that copper levels are low in NAFLD patients. Moreover, hepatic and serum copper levels are inversely correlated with the severity of NAFLD. Thus, high fructose consumption and low copper availability are considered two important risk factors in NAFLD. However, the causal effect of copper-fructose interactions as well as the effects of fructose intake on copper status remain to be evaluated in humans. The aim of this review is to summarize the role of copper-fructose interactions in the pathogenesis of the metabolic syndrome and discuss the potential underlying mechanisms. This review will shed light on the role of copper homeostasis and high fructose intake and point to copper-fructose interactions as novel mechanisms in the fructose induced NAFLD.

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