Excess Fructose Research Articles

Low-Intensity Exercise Affects Cardiac Fatty Acid Oxidation by Increasing the Nuclear Content of PPARα, FOXO1, and Lipin1 in Fructose-Fed Rats.

Background and Aim: Excessive fructose consumption along with a sedentary lifestyle provokes metabolic disorders and cardiovascular diseases. Fructose overload causes cardiac insulin resistance and increases reliance on fatty acid (FA) uptake and catabolism. The cardiometabolic benefits of exercise training have long been appreciated. The goal of the presented study is to shed a new light to the preventive role of exercise training on cardiac lipid metabolism in fructose-fed rats. Methods: Male Wistar rats were divided into control (C), sedentary fructose (F), and exercised fructose (EF) groups. Fructose was given as a 10% fructose solution in drinking water for 9 weeks. Low-intensity exercise training was applied for 9 weeks. The protein expression and subcellular localization of Lipin1, peroxisome proliferator-activated receptor α (PPARα), and peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC1) were analyzed in the heart using Western blot. Cardiac forkhead box transcription factor 1 (FOXO1) and sirtuin 1 (SIRT1) protein levels were also evaluated. Gene expression of long-chain acyl-CoA dehydrogenase was analyzed by quantitative polymerase chain reaction. Results: Exercise training has augmented the expression of main regulators of FA oxidation in the heart and achieves its effect by increasing the nuclear content of PPARα, Lipin1, and FOXO1 compared with the fructose group (P = 0.0422, P = 0.000045, P = 0.00958, respectively). In addition, Lipin1, FOXO1, and SIRT1 were increased in nuclear extract after exercise compared with the control group (P = 0.000043, P = 0.0417, P = 0.0329, respectively). In cardiac lysate, low-intensity exercise caused significantly increased protein level of PPARα, PGC1, FOXO1, and SIRT1 compared with control (P = 0.0377, P = 0.0275, P = 0.0096, P = 0.0282, respectively) and PGC1 level compared with the fructose group (P = 0.0417). Conclusion: The obtained results imply that the heart with a metabolic burden additionally relies on FA as an energy substrate after low-intensity running.

High Consumption of Lard and Fructose Modulates Larval Pupation and Stress Resistance in Drosophila Melanogaster Adults

Obesity and metabolic syndrome are becoming the number one health problem in modern society. Unhealthy diet with sedentary life style are considered to be the main causes of obesity. Food with excessive fat and fructose play an important role here. The aim of this work was to study the effects of feeding with lard, as a source of fat, or fructose, as a source of carbohydrates, on physiological and biochemical parameters of the fruit fly Drosophila melanogaster Canton S. The addition of 10% lard to the basic medium containing 5% fructose inhibited pupation of Canton S larvae. Medium with 15% fructose did not affect larval pupation rate. One-week feeding with medium containing 10% lard reduced climbing activity in 9-day-old Canton S males. In addition, food with 15% lard reduced climbing activity in female flies. One-week feeding with high fructose medium (15% fructose) did not affect climbing activity of flies of both sexes. Both high calorie diets, with lard and fructose, significantly increased the resistance of males to cold stress (measured by reducing time required for recovery from chill coma), but reduced heat stress resistance (determined by faster onset in heat coma at 40°C) in both sexes. The resistance of insects to starvation was reduced on high lard medium but not on fructose one. Foods enriched with fructose or lard did not affect food consumption, body masses and triacylglyceride content and levels of low- and high-molecular thiols in 9-day-old of flies of both sexes. In addition, feeding with high lard resulted in a downward trend in lower glucose and glycogen levels, whereas high fructose had the opposite effects. Thus, foods with high fructose and lard modulated stress resistance in adult flies and may affect energy metabolism. Detailed mechanisms underlying physiological effects of high fructose and lard in Drosophila needs further research.

Aerobic exercise prevents cardiomyocyte damage caused by oxidative stress in early cardiovascular disease by increasing vascularity while L-arginine supplementation prevents it by increasing activation of the enzyme nitric oxide synthase.

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.

Novel Biomarker Establishment for Evaluation of Excessive Fructose Consumption Using a Rat Model.

The habitual consumption of excessive fructose is associated with the onset and progression of lifestyle-related diseases, such as nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the physiological changes observed when consuming a diet containing excessive fructose on the viewpoints of hepatotoxicity biological markers using a rat model and explored the biomarker candidates that could detect the effects of excessive fructose intake at an early stage. Male rats were fed 63% high fructose diet (HFrD) ad libitum and their blood samples were collected before and at 1, 2, 3, and 4 weeks after allocation. The plasma biochemical parameters, hepatotoxic enzyme activities including alkaline phosphatase (ALP) isozymes were analyzed. HFrD consumption for 4-weeks created NAFLD-like symptoms, including elevated plasma lipid parameters and hepatotoxicity markers, as well as fat accumulation in the liver compared with rats consuming a control diet. Alanine aminotransferase (ALT) and glutamate dehydrogenase (GLDH) were increased from the 3rd and 2nd weeks, respectively, but no changes were observed on ALP activity. However, the daily consumption of the HFrD increased the plasma activities of liver-type ALP isozyme, and decreased plasma small intestinal-type ALP isozyme soon after the start of feeding. ALP isozyme analysis in combination with GLDH and ALT activities in the plasma samples could be a useful tool to detect the physiological changes induced by excessive fructose intake at an early stage of the development of NAFLD.

Food contributing to fermentable oligosaccharide, disaccharide, monosaccharide, and polyols intake in Korean adults.

The dietary intake of foods with fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is known to adversely affect patients with irritable bowel syndrome (IBS). However, the effects of FODMAP have been studied predominantly among Western populations. This study aimed to identify foods high in FODMAP content which form a part of the Korean adult diet and obtain basic data for the preparation of IBS guidelines. An online survey of 1,000 adults from the general population in the age group of 20 to 40 years was performed. Data from 787 participants (men, 386; women, 401) were analyzed. The general characteristics of the participants, health status, IBS diagnosis using the Rome III diagnostic criteria, semi-quantitative food frequency questionnaire findings, and food items causing symptoms were analyzed. Overall, 169 participants (21.5%) had IBS. The contribution of the FODMAP nutrients in both IBS and healthy groups was as follows: fructan > lactose > excess fructose > sorbitol > mannitol > galacto-oligosaccharides (GOS). The fructan intake was 4.6 ± 2.2 g/day and 4.3 ± 2.5 g/day in the IBS and healthy groups (P = 0.014), respectively. In the IBS group, the ratio of the intake of fructan to the total FODMAP intake was 39.5%, 29.8%, and 5.8% through onions, garlic, and bananas, respectively. Fructan was the FODMAP nutrient most consumed by Korean adults. Therefore, given the difference in the dietary habits of each country's population, the dietary guidelines for IBS should be country specific.

Active-phase Plasma Alkaline Phosphatase Isozyme Activity Is a Sensitive Biomarker for Excessive Fructose Intake.

Excessive fructose intake reportedly leads to the development of nonalcoholic fatty liver disease (NAFLD). In our previous study, we reported that plasma activities of alkaline phosphatase (ALP) isozymes were markedly changed in rats with excessive fructose intake-induced hepatomegaly. In this study, we examined ALP isozyme activity prior to the occurrence of hepatomegaly, and investigated the effect of the timing of sample collection, to explore its potential as a biomarker. After 1-week intake of a 63% high-fructose diet (HFrD), blood samples were collected from male rats during sleep or active phases to analyze biochemical parameters. Body and liver weights were similar between the HFrD and control diet groups, indicating that hepatomegaly due to excessive fructose intake had not occurred. The triglyceride levels and glutamate dehydrogenase (GLDH) activity were significantly elevated to similar degrees at both time points. HFrD intake significantly increased liver-type ALP (L-ALP) activity, stimulating it by 12.7% at the sleep phase and by 124.3% at the active phase. HFrD consumption also significantly decreased intestinal-type ALP (I-ALP) at the active phase, but only showed a decreasing trend during the sleep phase. Measurements of plasma ALP isozyme and GLDH activity, and triglyceride levels are effective early biomarkers of impending NAFLD caused by excessive fructose intake. L-ALP and I-ALP activities during the active phase are particularly sensitive for detection of excessive fructose intake before the occurrence of NAFLD.

Effect of Dietary Counseling on Patients with Asymptomatic Hyperuricemia

In Japan, hyperuricemia is on the rise. The guideline for the management of hyperuricemia and gout recommends lifestyle changes before beginning drug therapy. This study aimed to evaluate the effectiveness of dietary counseling following the guideline. Thirty-three subjects (24 men and 9 women) with asymptomatic hyperuricemia underwent dietary counseling for 6 months based on the following recommendations : (1) prevent excessive purine intake, (2) prevent excessive fructose intake, (3) limit alcohol drinking, and (4) drink sufficient water. Obese subjects were counseled on adequate energy intake. Blood sampling, anthropometric measurements, dietary surveys, and 24-h urine collection were performed at baseline and at 6 months. Serum uric acid (S-UA) levels were significantly lower at 6 months compared to baseline. Water intake and urine volume were considerably higher at 6 months than at baseline. When compared to baseline, urine UA (U-UA) levels were significantly lower, and renal fractional excretion of UA (FEUA) was significantly higher at 6 months. Changes in renal function (serum creatinine, estimated glomerular filtration rate, and FEUA) were significantly associated with ?S-UA level. In this study, S-UA level was significantly decreased by dietary counseling in line with the guideline. This study illustrates the effectiveness of dietary counseling for asymptomatic hyperuricemia. J. Med. Invest. 70 : 34-40, February, 2023.

High-Fructose Diet Induces Cardiac Dysfunction via Macrophage Recruitment in Adult Mice.

Cardiovascular diseases are the leading cause of death globally, including cardiac fibrosis, myocardial infarction, cardiac hypertrophy, and heart failure. High fat/ fructose induces metabolic syndrome, hypertension and obesity, which contributes to cardiac hypertrophy and fibrosis. Excessive fructose intake accelerates inflammation in different organs and tissues, and molecular and cellular mechanisms of organ and tissue injury have been demonstrated. However, the mechanisms of cardiac inflammation have not been fully documented in high-fructose diet. This study shows that there are significantly increased in cardiomyocytes size and relative wall thickness of LV in high-fructose fed adult mice. With echocardiographic analysis of cardiac function, the ejection fraction (EF%) and fractional shortening (FS%) are significantly reduced at 12 weeks after 60% high-fructose diet. The mRNA and protein levels of MCP-1 are notably increased in high-fructose treated HL-1 and primary cardiomyocyte respectively. Also, the increased protein level of MCP-1 has been detected in vivo mouse model after 12 weeks feeding, resulting in the production of pro-inflammatory makers, pro-fibrotic genes expression, and macrophage infiltration. These data demonstrate that high-fructose intake induces cardiac inflammation via macrophage recruitment in cardiomyocyte, which contributes to impair cardiac function.

Fructose might be a clue to the origin of preeclampsia insights from nature and evolution.

Preeclampsia is a hypertensive disorder of pregnancy and is due to abnormal placentation. The pathogenesis remains unclear. Fructose is biologically distinct from glucose and has a critical role in fetal growth in early pregnancy. Many species, including humans, produce fructose in their placenta during the first trimester to assist fetal growth and survival during a time when hypoxia is significant. Fructose is preferred over glucose in hypoxic tissues, and in the developing fetus, fructose has a critical role in stimulating the production of nucleic acids, lipids and glycosaminoglycans. Fructose production normally decreases significantly following the establishment of maternal-fetal circulation following placentation. However, if there is impaired placentation, local hypoxia will continue to drive fructose production. Excessive fructose metabolism drives endothelial dysfunction, oxidative stress, elevated blood pressure, insulin resistance, fatty liver, and a rise in uric acid and vasopressin levels, all of which are features of the preeclamptic state. In addition to fructose production, dietary fructose, for example, from soft drinks, would be additive and has been reported to be a strong independent risk factor for preeclampsia. Uric acid-associated endothelial dysfunction disturbs the invasion of the spiral artery, leading to placental ischemia and further placental hypoxia. Here, we summarize the previous literature regarding the physiological and pathological roles of fructose in pregnancy and propose studies to further investigate the pathogenesis of preeclampsia. Fructose might be a Clue to the Origin of Preeclampsia Insights from Nature and Evolution Preeclampsia is a hypertensive disorder of pregnancy. The pathogenesis remains unclear. Fructose has a critical role in fetal growth in early pregnancy, and might be a key role to developing preeclampsia. Here, we summarize the previous literatures regarding the physiological andpathological roles of fructose in pregnancy to propose studies to further investigate the pathogenesis of preeclampsia.

Naringin attenuates fructose-induced NAFLD progression in rats through reducing endogenous triglyceride synthesis and activating the Nrf2/HO-1 pathway.

Background: Excessive fructose consumption causes hepatic lipid accumulation via increased triglyceride (TG) synthesis, leading to the development and progression of non-alcoholic fatty liver disease (NALFD). Naringin, a flavanone glycoside found in citrus fruit, has antioxidant and hypolipidemic properties. Therefore, the aim of this study was to investigate the effect of naringin on fructose-induced NAFLD in rats and the possible underlying mechanism. Methods: Male Sprague Dawley rats were given 10% (w/v) fructose in drinking water for 12weeks. Naringin (100mg/kg/day) was administered orally to rats for the last 4weeks of fructose overload. After 12weeks of treatment, the hepatic lipid content was determined. In addition, the expression of proteins involved in de novo lipogenesis (DNL) and TG synthesis as well as antioxidant and inflammatory mediators in the liver were examined by western blot analysis. Results: Treatment of fructose-fed rats with naringin significantly decreased the hepatic TG and cholesterol content as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Naringin treatment also decreased the hepatic expression of carbohydrate response element binding protein (ChREBP), sterol regulatory element-binding protein-1c (SREBP-1c) and nuclear SREBP-1c (nSREBP-1c) as well as enzymes involved in DNL (acetyl CoA carboxylase [ACC] and fatty acid synthase [FAS]) and an enzyme involved in TG synthesis (glycerol-3-phosphate acyltransferase 1 [GPAT-1] and diacylglycerol acyltransferase2 [DGAT2]) in fructose-fed rats. In addition, naringin induced a significant decrease in the hepatic expression of nuclear factor kappa B (NF-κB) and tumor necrosis factor α (TNF-α). Furthermore, naringin administration restored the expression of the antioxidant mediators nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) in the liver of fructose-fed rats. Conclusion: These results demonstrate that oral administration of naringin protects against fructose-induced hepatic steatosis by decreasing DNL and TG synthesis. In addition, naringin could prevent NAFLD progression via targeting the Nrf2/HO-1 and the NF-κB/TNF-α pathways.

Association of Increased Fructose Consumption with Atrial Fibrillation Symptoms

Atrial fibrillation (AF) is the most common and increasingly common rhythm disorder . There is the AF classification model accepted by the European Society of Cardiology (ESC) and the European Heart Rhythm Society (EHRA) and the EHRA score (mEHRA score) for the evaluation of AF symptoms. Apart from its carbohydrate role, dietary fructose (as sucrose or high fructose corn syrup) has come to the fore in nutrition and dietetic studies whether it can be considered harmful or even a toxin by nature. High fructose consumption induces oxidative stress and thus causes mitochondrial damage in cells. In the light of this information, it is thought that high fructose consumption triggers mitochondrial dysfunction, which causes skeletal specific cells to enter the apoptosis pathway, by oxidative stress. Chronic fructose intake is thought to cause metabolic diseases and heart inflammation. Fructose consumption is the main dietary sugar that causes the progression of cardiovascular diseases and cardiac arrhythmias. AF patients admitted to the outpatient clinic were retrospectively scanned from the archive. Four groups of 40 patients were formed randomly according to EHRA scoring. Participants used a dietary record to provide details of nutrient consumption and all of the data from the 2 groups were compared. This study revealed statistically that a relationship between fructose consumption level and increased AF symptoms and mEHRA score (p<0,001), left atrium diameter and mEHRA score (p<0,001). Increased fructose consumption has been associated with increased AF symptoms. Excessive fructose consumption may play a role in AF pathophysiology.

Maternal Fructose Intake, Programmed Mitochondrial Function and Predisposition to Adult Disease.

Fructose consumption is now recognised as a major risk factor in the development of metabolic diseases, such as hyperlipidaemia, diabetes, non-alcoholic fatty liver disease and obesity. In addition to environmental, social, and genetic factors, an unfavourable intrauterine environment is now also recognised as an important factor in the progression of, or susceptibility to, metabolic disease during adulthood. Developmental trajectory in the short term, in response to nutrient restriction or excessive nutrient availability, may promote adaptation that serves to maintain organ functionality necessary for immediate survival and foetal development. Consequently, this may lead to decreased function of organ systems when presented with an unfavourable neonatal, adolescent and/or adult nutritional environment. These early events may exacerbate susceptibility to later-life disease since sub-optimal maternal nutrition increases the risk of non-communicable diseases (NCDs) in future generations. Earlier dietary interventions, implemented in pregnant mothers or those considering pregnancy, may have added benefit. Although, the mechanisms by which maternal diets high in fructose and the vertical transmission of maternal metabolic phenotype may lead to the predisposition to adult disease are poorly understood. In this review, we will discuss the potential contribution of excessive fructose intake during pregnancy and how this may lead to developmental reprogramming of mitochondrial function and predisposition to metabolic disease in offspring.

A high-fat, high-fructose diet induced hepatic steatosis, renal lesions, dyslipidemia, and hyperuricemia in non-obese rats

Excessive consumption of fat and sugar is associated with various chronic diseases. However, the variation of fat and sugar content in the diet greatly affected the outcome. In this study, a high-fat, high-fructose diet (HFHFD) formula was made with a composition of 31.99% carbohydrate, 40.7% fat, 11.8% protein, and an additional 30% fructose drink to confirm the effects of HFHFD on metabolic health and pathological changes in organs, especially the liver, kidneys, pancreas, muscles, and spleen. A total of 24 male Wistar rats aged 8–12 weeks were divided into four groups: standard chow (SC), HFHFD, SC + carbon tetrachloride (CCl4), and HFHFD + CCl4. After eight weeks of dietary intervention, body mass index, obesity index, lipid profiles, liver function tests, fasting blood glucose, serum uric acid and urea levels, and tissue histopathology were examined. HFHFD with the main unsaturated fatty acids of linoleic acid (14.57%) and palmitoleic acid (8.28%), the main saturated fatty acids of stearic acid (13.62%) and myristic acid (10.09%), and a low trans-fatty acids content, did not promote the rats to become obese. However, liver histology examination showed severe hepatic steatosis (78.33%), leading to steatohepatitis accompanied by an increase in serum ALP (p < 0.01), triglyceride (p < 0.001), total cholesterol (p < 0.05), and uric acid (p < 0.001) levels. Other histological features showed moderate lesions (45%) of the kidney, slight vacuolization of the pancreas, and a mild increase of inflammatory cells in the spleen and muscle. So, this study found that although HFHFD did not promote obesity within 8 weeks of administration, it induced hepatic and renal lesions, dyslipidemia, and hyperuricemia as a metabolic consequence of excessive fatty acids and fructose.

Negative Effects of Chronic High Intake of Fructose on Lung Diseases.

In the modern diet, excessive fructose intake (>50 g/day) had been driven by the increase, in recent decades, of the consumption of sugar-sweetened beverages. This phenomenon has dramatically increased within the Caribbean and Latin American regions. Epidemiological studies show that chronic high intake of fructose related to sugar-sweetened beverages increases the risk of developing several non-communicable diseases, such as chronic obstructive pulmonary disease and asthma, and may also contribute to the exacerbation of lung diseases, such as COVID-19. Evidence supports several mechanisms—such as dysregulation of the renin–angiotensin system, increased uric acid production, induction of aldose reductase activity, production of advanced glycation end-products, and activation of the mTORC1 pathway—that can be implicated in lung damage. This review addresses how these pathophysiologic and molecular mechanisms may explain the lung damage resulting from high intake of fructose.

How Fructose Affects the Hippocampus

This review explores the effects of fructose on the hippocampus: hippocampal function and structure, hippocampal neurogenesis, and hippocampal cognitive function. First, this result confirms that excess fructose intake affects the microstructure of pathways connecting the hippocampus to other brain areas. Fructose has the potential to affect neurogenesis in the hippocampus, and a diet high in fructose can impair learning and memory, leading to cognitive impairment. However, further research is needed to apply animal experiments to humans in the future. The literature review focused on the effects of fructose, but a balanced intake of other nutrients also needed to be considered.

Excessive fructose intake inhibits skeletal development in adolescent rats via gut microbiota and energy metabolism.

Excessive fructose intake from desserts and beverages may influence bone development among adolescents. The gut microbiota (GM) and energy metabolism play important roles in bone development. In this study, 40 female adolescent rats were randomly assigned to the control group, the fructose group with two concentrations, and the glucose group as the positive control group. After 10 weeks, serum glucose and lipids were detected by means of an automatic analyzer, and the bone microstructure was analyzed by Micro-CT. Then, the GM was determined via 16S rRNA sequencing analysis, and energy metabolism was detected by measuring serum carbohydrate metabolites. At last, bone metabolism markers were measured via ELISA kits. The results showed that excessive fructose intake could increase body weight and influence the glucolipid metabolism of female adolescent rats. Meanwhile, the bone microstructures were impaired with excessive fructose intake. Mechanistically, excessive fructose intake shifted the GM of rats with the decrease of Lachnospiraceae, Ruminococcaceae, and increase of Allobaculum, Lachnospiraceae. Energy metabolism analysis suggested that most metabolites of fructose did not enter the tricarboxylic acid cycle to provide energy for the body’s development. Furthermore, serum bone metabolism markers showed that excessive fructose intake could decrease both bone formation and resorption. Our results suggested that excessive fructose intake could inhibit skeletal development in adolescents. One potential mechanism might be that it affected the intestinal microbiota homeostasis in the juvenile body, thus changing the energy metabolism level, and ultimately affecting the bone metabolic balance.

Metformin alleviates long-term high-fructose diet-induced skeletal muscle insulin resistance in rats by regulating purine nucleotide cycle

Nutrient excess caused by excessive fructose intake can lead to insulin resistance and dyslipidemia, which further causes the development of metabolic syndrome. Metformin is a well-known AMPK activator widely used for the treatment of metabolic syndrome, while the mechanism of AMPK activation remains unclear. The present study aimed to investigate the pharmacological effects of metformin on fructose-induced insulin resistance rat, and the potential mechanism underlying AMPK activation in skeletal muscle tissue. Results indicated that metformin significantly ameliorated features of insulin resistance, including body weight, Lee's index, hyperinsulinemia, dyslipidemia, insulin intolerance and pancreatic damage. Moreover, treatment with metformin attenuated the inflammatory response in serum and enhanced the antioxidant capacity in skeletal muscle tissue. The therapeutic effects of metformin on fructose-induced insulin resistance may be related to the activation of AMPK to regulate Nrf2 pathway and mitochondrial abnormality. Additionally, metformin suppressed the expression of adenosine monophosphate deaminase 1 (AMPD1) and up-regulated the expression of adenylosuccinate synthetase (ADSS) in the purine nucleotide cycle (PNC), which facilitated the increase of AMP level and the ratio of AMP/ATP. Therefore, we proposed a novel mechanism that metformin activated AMPK via increasing AMP by regulating the expression of AMPD1 and ADSS in PNC pathway.

Maternal fructose intake during pregnancy and lactation: Later effects on renal function.

Excessive fructose consumption has been associated with hypertension and metabolic disorders and can alter physiological adaptations during pregnancy, with long‐term detrimental consequences. This study evaluated in post‐weaning mothers the effects of increased fructose consumption during pregnancy and lactation on blood pressure and renal function. Female Wistar rats were assigned to one of four experimental groups: non‐pregnant control (NPC); pregnant control (PC); non‐pregnant fructose (NPF), and pregnant fructose (PF). Control rats had free access to food and water, while the fructose groups had free access to food and to a 20% fructose solution, over the time period of the experiment. The systolic BP and renal function parameters were measured at the end of the experimental period, one week after weaning (28 days after delivery). The results were presented as means ± standard error. Higher values of BP were observed in both pregnant and non‐pregnant rats treated with fructose compared to control. Creatinine clearance was reduced only in the PF group; however, both the PF and NPF groups had reduced Na+ and K+ excretions. In the PF group, there was also glomerular enlargement and changes in the media/lumen (M/L) ratio of interlobular arteries. Additionally, the PF group showed increased macrophage infiltration and expression of alpha‐SM‐actin and reduced expression of nitric‐oxide‐synthase endothelial in renal tissue. These findings suggest that the association of high fructose intake with pregnancy aggravated kidney changes that persisted for up to four weeks after delivery, which may represent a risk factor for maternal health.

Development and evaluation of novel rodent model of PCOS mimicking clinical phenotype in human disease

BackgroundPolycystic ovary syndrome is a most common female reproductive disorder, involving endocrine and metabolic disorders with unclear etiology. Androgen-based rodent animal models like DHEA and DHT are most suitable for PCOS induction, but still, these models fail to produce non-lean PCOS phenotypes such as hyperandrogenism, hyperinsulinemia, elevated estrogen levels, and ovary weight. Excess fructose consumption leads to hyperandrogenism, hyperinsulinemia, and insulin resistance. The purpose of this study is to investigate, whether fructose consumption along with androgens in rats, could develop all metabolic and endocrine phenotypes of non-lean human PCOS disease. MethodsPrepubertal SD rats were administered with DHT (83ug, s.c.) and fructose (20%, p.o.) for 90 days whereas DHEA (7 mg/kg, s.c) and fructose (20%, p.o.) for 30 days. During study duration, the blood glucose level for oral glucose tolerance test, estrus cyclicity, and ultrasonography was observed. Reproductive hormones LH, FSH, insulin, testosterone, and estradiol levels were assessed using ELISA. The ovary, uterus, abdominal fat, and subcutaneous fat were collected and weighed, and histopathology was done for any anomaly’s findings.ResultsDHT + fructose-treated rats showed significant (p < 0.05) increase in serum testosterone, LH, estradiol, decreased FSH levels, and caused multiple cystic follicles. Abdominal fat, subcutaneous fat, ovary, and uterine weight were higher in DHT + F and DHEA + F when compared to control groups. OGTT reveals impaired insulin sensitivity and glucose tolerance in both model groups. Ovarian histopathology of DHT + F shows more cysts than the DHEA + F groups. No significant changes in uterine histology of DHT + F and DHEA + F-treated rats.ConclusionDHT + F-treated rats mimic all clinical phenotypes and could be used as novel rodent model for non-lean type PCOS.

An experimental study to investigate the impact of Aspirin and Vitamin C therapy on fructose induced hepatic and pancreatic damage

It is assumed that excessive fructose consumption is associated with the risk of developing various diseases, especially metabolic disease. The aims of this study were two fold: 1) Does liver and pancreatic damage occur due to excessive fructose consumption 2) If damage occurs, can we reduce this damage by using (ASA) and Vit. C. The rats were divided randomly into five groups of eight as follows: Group1-control; Group2-corn syrup (Fructose: F; 30% F solution); Group3-F and ASA (F+10 mg/kg/day, ASA, oral); Group4-F and Vit. C (F+200 mg/kg/day, Vit. C, oral); Group5-F, ASA and Vit C (F+A+C -same dose administration, respectively). The rats were sacrificed 24 h after the last application at the end of the 6th week, and their blood serum, liver and pancreas tissues were taken and evaluated histologically and biochemically. It was found that serum cholesterol and AST levels were significantly lower in the F+C and F+A+C groups, and ALT and TG levels were significantly lower in the F+A+C group compared to the F group (p