Fructose Intake Research Articles

Identification of lead compound screened from the natural products atlas to treat renal inflammasomes using molecular docking and dynamics simulation

One of the most prevalent ailments is kidney disease. Effective therapies for chronic renal disease are hard to come by. As a result, there is significant clinical and social interest to predict and develop novel compounds to treat renal disorders. So, specific natural products have been employed in this study because they have protective effects against kidney diseases. When taken orally, natural products can help protect against or lessen the severity of the kidney damage caused by high fructose intake, a high-fat diet, and both Type I and Type 2 diabetes. Reduced podocyte injury, a contributor to albuminuria in diabetic nephropathy, reduces renal endothelial barrier function disruption due to hyperglycemia, as well as urinary microalbumin excretion and glomerular hyperfiltration. Multiple natural products have been shown to protect the kidneys from nephrotoxic chemicals such as LPS, gentamycin, alcohol, nicotine, lead, and cadmium, all of which can persuade acute kidney injury (AKI) or chronic kidney disease (CKD). Natural compounds inhibit regulatory enzymes for controlling inflammation-related diseases. For this, use computational methods such as drug design to identify novel flavonoid compounds against kidney diseases. Drug design via computational methods gaining admiration as a swift and effective technique to identify lead compounds in a shorter time at a low cost. In this in-silico study, we screened The Natural Product Atlas based on a structure-based pharmacophore query. Top hits were analyzed for ADMET analysis followed by molecular docking and docking validation. Finally, the lead compound was simulated for a period of 200 ns and trajectories were studied for stability. We found that NPA024823 showed promising binding and stability with the AIM2. This research work aims to predict novel anti-inflammatory compounds against kidney diseases to inhibit kidney inflammasome by targeting the AIM2 protein. So, in initial preclinical research, there will be lower failure rates that demonstrate safety profiles against predicted compounds. Communicated by Ramaswamy H. Sarma

Morroniside Delays NAFLD Progression in Fructose-Fed Mice by Normalizing Lipid Metabolism and Inhibiting the Inflammatory Response

Chronic fructose consumption is becoming one leading risk factor for NAFLD due to its hazard on cellular lipid metabolism, which plays an essential role in the pathogenesis of NAFLD. Morroniside, an iridoid glycoside from Cornus officinalis, has been suggested to have potent in regulating cellular glucolipid metabolism. However, the effect and mechanism of morroniside on improving fructose-induced hepatic steatosis and retarding NAFLD progression remain ambiguous. In this study, we illustrate the efficacy of morroniside in alleviating fructose-triggered hepatic steatosis in mice. Mechanically, morroniside suppressed de novo lipogenesis and promoted β-oxidation by inhibiting the activation of PGC1β. Additionally, morroniside was found to work in attenuating hepatic inflammation in response to long-term fructose intake. Taken together, the current study reveals that morroniside is a promising food and medicinal therapy for NAFLD treatment and is effective in delaying the progression of NAFLD to NASH, especially in subtypes caused by excessive carbohydrate intake.

Effect of high-fructose consumption in pregnancy on the bone growth of offspring rats.

Growing evidence suggests that bone health is programmed in early life. Maternal diet may influence the skeletal development of offspring. We aimed to determine the possible effects of high-fructose intake during pregnancy on different aspects of long bone morphology in the offspring of rats and to initially explore the possible mechanisms. Pregnant Sprague-Dawley rats were randomly divided into four groups and intragastrically administered the same dose of distilled water (CON, n = 12), 20 g/kg/day glucose (GLU, n = 12), 10 g/kg/day fructose (LFRU, n = 12), or 20 g/kg/day fructose (HFRU, n = 12) for 21 days during gestation. Computed tomography was used to analyze the cortical and cancellous bones of the distal femur of the offspring rats, and circulating bone metabolic biomarkers were measured using enzyme immunoassay. The results showed that high-fructose intake during pregnancy could decrease body weight, impair glucose metabolism, and increase serum leptin and uric acid in offspring. The offspring in the HFRU group had higher levels of the N-terminal propeptide of type I procollagen (PINP) and the C-telopeptide of type I collagen (CTX). The bone mean density (BMD), the total cross-sectional area inside the periosteal envelope (Tt.Ar), cortical bone area (Ct.Ar), medullary (or marrow) area (Ma.Ar), and trabecular mean density of the offspring in the HFRU group were lower than those in the CON group. Tartrate-resistant acid phosphatase (Trap) staining showed that high-fructose intake during pregnancy could increase the number of osteoclasts and increase the absorption area. Our results suggested that excessive fructose intake during pregnancy could inhibit skeletal development in offspring. Thus, attention to fructose intake during pregnancy is important for bone development in offspring.

The potential therapeutic roles of quercetin and luteolin in hereditary fructose intolerance

Hereditary fructose intolerance (HFI) is a genetic condition caused by a deficiency in the aldolase B enzyme. Patients with HFI are sensitive to fructose, and exposure to fructose can cause symptoms ranging from nausea to death. Treatment of HFI is currently limited to dietary restriction of fructose intake. However, emerging evidence indicates that dietary restriction is insufficient to fully protect patients from the adverse consequences of HFI. Despite strict dietary adherence, patients with HFI are more likely than the general population to develop non-alcoholic fatty liver disease and insulin resistance. This review proposes and examines evidence supporting the hypothesis that quercetin and luteolin, two inexpensive and widely available supplements, may mitigate the sequelae of HFI by inhibiting gastrointestinal fructose uptake and inhibiting endogenous fructose production. It further explores the additional hypothesis that quercetin and luteolin may mitigate the harms associated with a high-fructose diet in the general, fructose-tolerant populace.

The impact of dietary fructose on gut permeability, microbiota, abdominal adiposity, insulin signaling and reproductive function

The excessive intake of fructose in the regular human diet could be related to global increases in metabolic disorders. Sugar-sweetened soft drinks, mostly consumed by children, adolescents, and young adults, are the main source of added fructose. Dietary high-fructose can increase intestinal permeability and circulatory endotoxin by changing the gut barrier function and microbial composition. Excess fructose transports to the liver and then triggers inflammation as well as de novo lipogenesis leading to hepatic steatosis. Fructose also induces fat deposition in adipose tissue by stimulating the expression of lipogenic genes, thus causing abdominal adiposity. Activation of the inflammatory pathway by fructose in target tissues is thought to contribute to the suppression of the insulin signaling pathway producing systemic insulin resistance. Moreover, there is some evidence that high intake of fructose negatively affects both male and female reproductive systems and may lead to infertility. This review addresses dietary high-fructose-induced deteriorations that are obvious, especially in gut permeability, microbiota, abdominal fat accumulation, insulin signaling, and reproductive function. The recognition of the detrimental effects of fructose and the development of relevant new public health policies are necessary in order to prevent diet-related metabolic disorders.

Fructose promotes angiogenesis by improving vascular endothelial cell function and upregulating VEGF expression in cancer cells

BackgroundFructose is a very common sugar found in natural foods, while current studies demonstrate that high fructose intake is significantly associated with increased risk of multiple cancers and more aggressive tumor behavior, but the relevant mechanisms are not fully understood.MethodsTumor-grafting experiments and in vitro angiogenesis assays were conducted to detect the effect of fructose and the conditioned medium of fructose-cultured tumor cells on biological function of vascular endothelial cells (VECs) and angiogenesis. 448 colorectal cancer specimens were utilized to analyze the relationship between Glut5 expression levels in VECs and tumor cells and microvascular density (MVD).ResultsWe found that fructose can be metabolized by VECs and activate the Akt and Src signaling pathways, thereby enhancing the proliferation, migration, and tube-forming abilities of VECs and thereby promoting angiogenesis. Moreover, fructose can also improve the expression of vascular endothelial growth factor (VEGF) by upregulating the production of reactive oxygen species (ROS) in colorectal cancer cells, thus indirectly enhancing the biological function of VECs. Furthermore, this pro-angiogenic effect of fructose metabolism has also been well validated in clinical colorectal cancer tissues and mouse models. Fructose contributes to angiogenesis in mouse subcutaneous tumor grafts, and MVD is positively correlated with Glut5 expression levels of both endothelial cells and tumor cells of human colorectal cancer specimens.ConclusionsThese findings establish the direct role and mechanism by which fructose promotes tumor progression through increased angiogenesis, and provide reliable evidence for a better understanding of tumor metabolic reprogramming.

The fructose survival hypothesis for obesity.

The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) that aims to protect animals in advance of crisis. The response is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation and increased blood pressure. The process is initiated by the ingestion of fructose or by stimulating endogenous fructose production via the polyol pathway. Unlike other nutrients, fructose reduces the active energy (adenosine triphosphate) in the cell, while blocking its regeneration from fat stores. This is mediated by intracellular uric acid, mitochondrial oxidative stress, the inhibition of AMP kinase and stimulation of vasopressin. Mitochondrial oxidative phosphorylation is suppressed, and glycolysis stimulated. While this response is aimed to be modest and short-lived, the response in humans is exaggerated due to gain of 'thrifty genes' coupled with a western diet rich in foods that contain or generate fructose. We propose excessive fructose metabolism not only explains obesity but the epidemics of diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular and Alzheimer's dementia, and even ageing. Moreover, the hypothesis unites current hypotheses on obesity. Reducing activation and/or blocking this pathway and stimulating mitochondrial regeneration may benefit health-span. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Determining the metabolic effects of dietary fat, sugars and fat-sugar interaction using nutritional geometry in a dietary challenge study with male mice

The metabolic effects of sugars and fat lie at the heart of the “carbohydrate vs fat” debate on the global obesity epidemic. Here, we use nutritional geometry to systematically investigate the interaction between dietary fat and the major monosaccharides, fructose and glucose, and their impact on body composition and metabolic health. Male mice (n = 245) are maintained on one of 18 isocaloric diets for 18–19 weeks and their metabolic status is assessed through in vivo procedures and by in vitro assays involving harvested tissue samples. We find that in the setting of low and medium dietary fat content, a 50:50 mixture of fructose and glucose (similar to high-fructose corn syrup) is more obesogenic and metabolically adverse than when either monosaccharide is consumed alone. With increasing dietary fat content, the effects of dietary sugar composition on metabolic status become less pronounced. Moreover, higher fat intake is more harmful for glucose tolerance and insulin sensitivity irrespective of the sugar mix consumed. The type of fat consumed (soy oil vs lard) does not modify these outcomes. Our work shows that both dietary fat and sugars can lead to adverse metabolic outcomes, depending on the dietary context. This study shows how the principles of the two seemingly conflicting models of obesity (the “energy balance model” and the “carbohydrate insulin model”) can be valid, and it will help in progressing towards a unified model of obesity. The main limitations of this study include the use of male mice of a single strain, and not testing the metabolic effects of fructose intake via sugary drinks, which are strongly linked to human obesity.

Traditional lifestyle factors partly mediate the association of socioeconomic position with intrahepatic lipid content: The Maastricht study

Recent studies have unveiled an association between socioeconomic position (SEP) and intrahepatic lipid (IHL) content. The aim of this study was to examine to what extent traditional lifestyle factors mediate the relationship between SEP and IHL content, independent of aetiology, and non-alcoholic fatty liver disease (NAFLD). We used cross-sectional data derived from The Maastricht Study (N= 4,001; mean age: 60 years, 49% women, 32% low education level, 21% diabetes, 21% NAFLD). Education, income, and occupation were used as indicators of SEP. Physical activity (accelerometer), intake of total energy, alcohol, saturated fat, protein, vitamin E, dietary fibre, and fructose from sugar-sweetened beverages (SSBs) and fruit juice (food frequency questionnaires) were potential mediators. IHL content was quantified by magnetic resonance imaging. Age, sex, and type 2 diabetes were covariates. Multiple parallel mediation analyses (bootstraps= 10,000) were performed. Individuals with a low education level had a 1.056-fold higher IHL content (95% CI: 1.03-1.08) and a 44% greater NAFLD risk (OR:1.44; 95% CI:1.18-1.77) compared with those with higher education levels. Approximately 8.9% of educational disparity in risk of IHL content was attributable to moderate-to-vigorous physical activity; 6.3% to fructose intake from SSBs; 5.5% to dietary fibre; and -23% to alcohol. Approximately 8.7% of educational disparity in risk of NAFLD was attributable to moderate-to-vigorous physical activity; and 7.7% to fructose intake from SSBs. However, the indirect effect of these mediators was small (0.998 for IHL content and 1.045 for NAFLD) in comparison to the total effect. Similar results were found when income and occupation were used as SEP indicators. Societal measures may alleviate the burden of NAFLD and further studies that identify mediators other than traditional lifestyle factors are warranted to define the relationship underlying SEP and IHL content. Individuals with a low or medium level of education, income, or occupational status had more fat accumulation in their livers than individuals with a higher education, income, or occupational status. This difference may be attributed to the influence of unhealthy lifestyle factors, such as reduced physical activity and a higher intake of sugar-sweetened beverages among individuals with lower socioeconomic position. Nevertheless, other yet unknown factors may also play a role.

Long-term high fructose intake promotes lacrimal gland dysfunction by inducing gut dysbiosis in mice

The lacrimal gland is essential for maintaining ocular surface health through the secretion of the aqueous layer of the tear film. It is therefore important to explore the intrinsic and extrinsic factors that affect the structure and function of the lacrimal gland and the mechanisms underlying them. With the prevalence of Westernized diets characterized by high sugar and fat content, the susceptibility to many diseases, including ocular diseases, is increased by inducing dysbiosis of the gut microbiome. Here, we found that the composition, abundance, and diversity of the gut microbiome was significantly altered in mice by drinking 15% high fructose water for one month, as determined by 16S rRNA sequencing. This was accompanied by a significant increase in lipid deposition and inflammatory cell infiltration in the extraorbital lacrimal glands (ELGs) of mice. Transcriptome analysis based on bulk RNA-sequencing revealed abnormal activation of some of several metabolic and immune-related pathways. In addition, the secretory response to stimulation with the cholinergic receptor agonist pilocarpine was significantly reduced. However, when the composition and diversity of the gut microbiome of high fructose intake (HFI)-treated mice were improved by transplanting feces from normal young healthy mice, the pathological alterations in ELG structure, inflammatory cell infiltration, secretory function and transcriptome analysis described above were significantly reversed compared to age-matched control mice. In conclusion, our data suggest that prolonged HFI may cause pathological damage to the structure and function of the ELG through the induction of gut dysbiosis. Restoration of intestinal dysbiosis in HFI-treated mice by fecal transplantation has a potential role in ameliorating these pathological impairments.

Lipid peroxidation and neuroinflammation: A possible link between maternal fructose intake and delay of acquisition of neonatal reflexes in Wistar female rats.

Fructose is a common sweetener found in the daily diet supplemented to many processed and ultra-processed foods and beverages. Consumption of fructose-sweetened beverages has drastically increased in the last decades and is widely associated with metabolic disease, systemic pro-inflammatory status, and adverse transgenerational effects. To date, the impact of maternal fructose intake in brain function of the offspring is less explored. Therefore, the aim of this study was first, to investigate adverse effects in developmental milestones of the progeny of mothers with metabolic syndrome (MetS), induced by ad libitum consumption of a 20% fructose solution, and second to identify possible molecular changes in the nervous system of the newborns associated with maternal fructose intake. Wistar rats were randomly separated into two groups with access to water or fructose (20% w/v in water) for 10 weeks. After MetS was confirmed, dams were mated with control males and continued drinking water or fructose solution during gestation. At postnatal day (PN) 1, a subgroup of offspring of each sex was sacrificed and brains were dissected for oxidative stress and inflammatory status analysis. Changes in the developmental milestones due to maternal fructose consumption were studied (PN3-PN21) in another subgroup of offspring. Sexually dimorphic effects were found on the progeny's acquisition of neurodevelopmental milestones, in brain lipid peroxidation, neuroinflammation, and antioxidative defensive response. Our results suggest that dams' MetS, induced by fructose intake, disrupts brain redox homeostasis in female offspring and affects sensorimotor brain circuitry which may have a translational value for studying neurodevelopmental diseases.

Fructose Consumption Alters Biogenic Amines Associated with Cardiovascular Disease Risk Factors.

Cardiovascular diseases (CVD) are the major cause of mortality worldwide, whose most prominent risk factor is unhealthy eating habits, such as high fructose intake. Biogenic amines (BAs) perform important functions in the human body. However, the effect of fructose consumption on BA levels is still unclear, as is the association between these and CVD risk factors. This study aimed to establish the association between BA levels and CVD risk factors in animals that consumed fructose. Male Wistar rats received standard chow (n=8) or standard chow + fructose in drinking water (30%) (n=8) over a 24-week period. At the end of this period, the nutritional and metabolic syndrome (MS) parameters and plasmatic BA levels were analyzed. A 5% level of significance was adopted. Fructose consumption led to MS, reduced the levels of tryptophan and 5-hydroxitryptophan, and increased histamine. Tryptophan, histamine, and dopamine showed a correlation with metabolic syndrome parameters. Fructose consumption alters BAs associated with CVD risk factors.

Systematic Review on the Effects of Food on Mental Health via Gut Microbiome

Recent studies have suggested that diet may affect the gut microbiome, subsequently influencing mental health. While several systematic reviews have been done on the effects of diet on mental health via the gut microbiome, there are focused on either specific diets or mental disorders. This systematic review examines the effect of diet and broad-based mental health via the gut microbiome. 21 out of 99 studies published prior to 2023 and listed in PubMed are included. Our analysis suggests that a vegan diet, a Mediterranean-style diet, fiber, probiotics, dietary vitamin D, unpasteurized milk, foods with a low omega-3 to omega-6 ratio, and Xiao Yan Sanmay have positive effects on gut microbiome, leading to a positive influence on mental health, while a meat-rich diet, a high-fat diet, high fructose intake, and zinc deficiency may have negative effects on gut microbiome, leading to a negative influence on mental health. Collectively, the effects of diet on mental health via gut microbiome may be explained by the composition of gut microbiome and the metabolites produced by gut microbiome on gut permeability. Doi: 10.28991/SciMedJ-2023-05-02-05 Full Text: PDF

Can early-life high fructose exposure induce long-term depression and anxiety-like behaviours? – A preclinical systematic review

Early-life environmental factors, such as maternal diet or early-life nutrition, have been described as significant risk factors for anxiety and depression later in life. With the rising intake of fructose since the 1960 s, several adverse effects have been described, but little is known about the impact of early-life high fructose exposure on the risk of developing depression and anxiety later in life. Since animal models provide ways to test this hypothesis longitudinally in an experimental and controlled environment, we performed a systematic review to investigate whether high fructose exposure during early life influences the risk of developing depression or anxiety-like behaviours in animals. We adopted a high-sensitivity strategy to find potential studies. We included 1805 papers for screening, but only found nine eligible studies that tested only high fructose exposure during development, all conducted in rats. Data extraction and analysis revealed that 6 studies found evidence indicating that fructose exposure in early life increases the risk of anxiety or depression. The remaining 3 studies found no altered behavior after fructose exposure. The discrepancies may be caused by multiple factors, such as time of diet exposure, animal strain, behavioural testing differences, and fructose's metabolic influence. Due to weak and contradictory evidence, we could not conclude if early-life fructose exposure influences the risk of anxiety or depression-like behaviors. We propose future directions and suggestions for future studies to strengthen their findings.

Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD

Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome, and is estimated to affect one billion individuals worldwide. An increased intake of a high-fat diet (HFD) and sugar-sweetened beverages are risk-factors for NAFLD development, but how their combined intake promotes progression to a more severe form of liver injury is unknown. Here we show that fructose metabolism via ketohexokinase (KHK) C isoform leads to unresolved endoplasmic reticulum (ER) stress when coupled with a HFD intake. Conversely, a liver-specific knockdown of KHK in mice consuming fructose on a HFD is adequate to improve the NAFLD activity score and exert a profound effect on the hepatic transcriptome. Overexpression of KHK-C in cultured hepatocytes is sufficient to induce ER stress in fructose free media. Upregulation of KHK-C is also observed in mice with genetically induced obesity or metabolic dysfunction, whereas KHK knockdown in these mice improves metabolic function. Additionally, in over 100 inbred strains of male or female mice hepatic KHK expression correlates positively with adiposity, insulin resistance, and liver triglycerides. Similarly, in 241 human subjects and their controls, hepatic Khk expression is upregulated in early, but not late stages of NAFLD. In summary, we describe a novel role of KHK-C in triggering ER stress, which offers a mechanistic understanding of how the combined intake of fructose and a HFD propagates the development of metabolic complications.

Association of fructose consumption with prevalence of functional gastrointestinal disorders manifestations: results from Hellenic National Nutrition and Health Survey (HNNHS).

The study aimed to assess the total prevalence of functional gastrointestinal disorders (FGID), and separately, irritable bowel syndrome (IBS) among adults and to determine their potential association with fructose consumption. Data from the Hellenic National Nutrition and Health Survey were included (3798 adults; 58·9 % females). Information regarding FGID symptomatology was assessed using self-reported physician diagnosis questionnaires the reliability of which were screened using the ROME III, in a sample of the population. Fructose intake was estimated from 24 h recalls, and the MedDiet score was used to assess adherence to the Mediterranean diet. The prevalence of FGID symptomatology was 20·2 %, while 8·2 % had IBS (representing 40·2 % of total FGID). The likelihood of FGID was 28 % higher (95 %CI: 1·03-1·6) and of IBS 49 % (95 %CI: 1·08-2·05) in individuals with higher fructose intake than with lower intake (3rd tertile compared with 1st). When area of residence was accounted for, individuals residing in the Greek islands had a significantly lower probability of FGID and IBS compared with those residing in Mainland and the main Metropolitan areas, with Islanders also achieving a higher MedDiet score and lower added sugar intake, comparatively to inhabitants of the main metropolitan areas. FGID and IBS symptomatology was most prominent among individuals with higher fructose consumption, and this was most conspicuous in areas with a lower Mediterranean diet adherence, suggesting that the dietary source of fructose rather than total fructose should be examined in relation to FGID.

METABOLIC DYSFUNCTIONS CAUSED BY EARLY FRUCTOSE INGESTION ARE PREVENTED IN CONCURRENTLY EXERCISED ADULT MALE RATS

This study evaluated whether fructose ingestion at adolescence programs the development ofmetabolic syndrome (MetS) in adult rats and whether moderate-intensity combined exercisecan attenuate fructose-induced MetS compounds. Pubertal rats were trained on a treadmill(55-65% VO 2max ), 3 times/week, 44 min/session, for one month. They were allocated into fourgroups: sedentary control (SC), trained control (TC), sedentary fructose (SF), and trainedfructose (TF). Groups F ingested 10% fructose. Food intake (AI) and body weight (BW) weremeasured weekly. At 60 and 120 days of age, metabolic parameters were evaluated. Fructoseintake mainly affected animals in adult life, and these changes were related to glucoseintolerance (p=0.001), periepididymal fat (p<0.03), and increase in total cholesterol (TC) (p<0.001), triglycerides (TAGs) (p<0.0001) and insulin (p<0.0001) levels. Early physicalexercise was able to decrease periepididymal (p<0.003) and retroperitoneal (p<0.0002)adipose tissue, TC levels (p<0.0001) and glucose tolerance (p=0.21). Rats that receivedcombined treatments during adolescence showed low glycemia (p=0.003) and insulinemia(p<0.0001) during the intraperitoneal glucose tolerance test (ipGTT). HOMA-IR (p=0.02) andTYG (p=0.0003) scores also improved in these rats. We conclude that early ingestion of 10%fructose was effective in programming adult rats to MetS, and simultaneous moderateexercise attenuated these aggressions, causing changes in glycemic homeostasis and lipidmetabolism.

Dietary Factors and Pancreatic Cancer Risk: An Umbrella Review of Meta-Analyses of Prospective Observational Studies.

Dietary factors may be associated with the occurrence of pancreatic cancer. This umbrella review aimed to review and grade the evidence for the associations between dietary factors and pancreatic cancer risk. We searched PubMed, EMBASE, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and CINAHL for eligible literature. We included meta-analyses of randomized controlled trials (RCTs) or prospective observational studies. We used AMSTAR-2, a measurement tool to assess systematic reviews, to evaluate the methodological quality of the included meta-analyses. For each association, we calculated the summary effect size, 95% CI, heterogeneity, number of cases, 95% prediction interval, small-study effect, and excess significance bias. The protocol for this review was registered in the PROSPERO database (CRD42022333669). We included 41 meta-analyses of prospective observational studies describing 59 associations between dietary factors and pancreatic cancer risk. None of the retrieved meta-analyses included RCTs. No association was supported by convincing or highly suggestive evidence; however, there was suggestive evidence of a positive association between fructose intake and pancreatic cancer risk. There was weak evidence for an inverse association of nuts intake or adherence to the Mediterranean diet with pancreatic cancer incidence, and for positive associations between a higher intake of red meat or heavy alcohol intake and pancreatic cancer incidence. The remaining 54 associations were nonsignificant. Consistent with the American Institute for Cancer Research review, this umbrella review found that regular consumption of nuts and reduced intake of fructose, red meat, and alcohol were associated with a lower risk of pancreatic cancer. Emerging weak evidence supported an inverse association between adherence to the Mediterranean diet and pancreatic cancer risk. As some associations were rated as weak and most were considered nonsignificant, further prospective studies are needed to investigate the role of dietary factors and risk of pancreatic cancer.

Liver acts as a metabolic gate for the traumatic brain injury pathology: Protective action of thyroid hormone

Clinical evidence indicates that injury to the brain elicits systemic metabolic disturbances that contributes to the brain pathology. Since dietary fructose is metabolized in the liver, we explored mechanisms by which traumatic brain injury (TBI) and dietary fructose influence liver function and their possible repercussions to brain. Consumption of fructose contributed to the detrimental effects of TBI on liver operation, in terms of glucose and lipid metabolism, de novo lipogenesis, lipid peroxidation. Thyroid hormone (T4) is metabolized in the liver and found that T4 supply improved lipid metabolism by reducing de novo lipogenesis, lipid accumulation, lipogenic enzymes (ACC, AceCS1, FAS), lipid peroxidation in liver in response to fructose and fructose-TBI. T4 supply also helped to normalize glucose metabolism and improve insulin sensitivity. Furthermore, T4 counteracted elevations of the pro-inflammatory cytokines, Tnfα and Mcp-1 after TBI and/or fructose intake in liver and circulation. T4 also exerted an effect on isolated primary hepatocytes by potentiating phosphorylation of AMPKα and AKT substrate, AS160, leading to increased glucose uptake. In addition, T4 restored the metabolism of DHA in the liver disrupted by TBI and fructose, adding important information to optimize the action of DHA in therapeutics. The overall evidence seems to indicate that the liver works as a gate for the regulation of the effects of brain injury and foods on brain pathologies.

Fructose-induced salt-sensitive blood pressure differentially affects sympathetically mediated aortic stiffness in male and female Sprague-Dawley rats.

Hypertension is the leading risk factor for major adverse cardiovascular events (MACE). Aortic stiffness and sympathoexcitation are robust predictors of MACE. Combined high fructose and sodium intake increases arterial pressure, aortic stiffness, renin, and sympathetic nerve activity in male rats. We hypothesized that activation of the renin angiotensin system (RAS) and/or the sympathetic system mediates aortic stiffness in rats with fructose-induced salt-sensitive blood pressure. Male and female Sprague-Dawley rats ingested 20% fructose or 20% glucose in drinking water with 0.4% NaCl chow for 1 week. Then, fructose-fed rats were switched to 4% NaCl chow (Fru + HS); glucose-fed rats remained on 0.4% NaCl chow (Glu + NS, controls for caloric intake). After 2 weeks, mean arterial pressure (MAP) and aortic pulsed wave velocity (PWV) were evaluated at baseline or after acute intravenous vehicle, clonidine, enalapril, losartan, or hydrochlorothiazide. Baseline global longitudinal strain (GLS) was also assessed. MAP and PWV were greater in male Fru + HS versus Glu + NS male rats (p < 0.05 and p < 0.001, respectively). PWV was similar between the female groups. Despite similarly reduced MAP after clonidine, PWV decreased in Fru + HS versus Glu + NS male rats (p < 0.01). Clonidine induced similar decreases in MAP and PWV in females on either diet. GLS was lower in Fru + HS versus Glu + NS male rats and either of the female groups. Thus, acute sympathoinhibition improved aortic compliance in male rats with fructose salt-sensitive blood pressure. Female rats retained aortic compliance regardless of diet. Acute RAS inhibition exerted no significant effects. Male rats on fructose high salt diet displayed an early deficit in myocardial function. Taken together, these findings suggest that adult female rats are protected from the impact of fructose and high salt diet on blood pressure, aortic stiffness, and early left ventricular dysfunction compared with male rats.