Dataset Information

Dietary Fructose Intake and Hippocampal Structure and Connectivity during Childhood.

ABSTRACT: In rodent literature, there is evidence that excessive fructose consumption during development has a detrimental impact on hippocampal structure and function. In this study of 103 children ages 7-11 years old, we investigated whether dietary fructose intake was related to alterations in hippocampal volume and connectivity in humans. To examine if these associations were specific to fructose or were related to dietary sugars intake in general, we explored relationships between dietary intake of added sugars and the monosaccharide, glucose, on the same brain measures. We found that increased dietary intake of fructose, measured as a percentage of total calories, was associated with both an increase in the volume of the CA2/3 subfield of the right hippocampus and increased axial, radial, and mean diffusivity in the prefrontal connections of the right cingulum. These findings are consistent with the idea that increased fructose consumption during childhood may be associated with an inflammatory process, and/or decreases or delays in myelination and/or pruning. Increased habitual consumption of glucose or added sugar in general were associated with an increased volume of right CA2/3, but not with any changes in the connectivity of the hippocampus. These findings support animal data suggesting that higher dietary intake of added sugars, particularly fructose, are associated with alterations in hippocampal structure and connectivity during childhood.

SUBMITTER: Clark KA

PROVIDER: S-EPMC7230400 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dietary Fructose Intake and Hippocampal Structure and Connectivity during Childhood.

Clark Kristi A KA Alves Jasmin M JM Jones Sabrina S Yunker Alexandra G AG Luo Shan S Cabeen Ryan P RP Angelo Brendan B Xiang Anny H AH Page Kathleen A KA

Nutrients 20200326 4

In rodent literature, there is evidence that excessive fructose consumption during development has a detrimental impact on hippocampal structure and function. In this study of 103 children ages 7-11 years old, we investigated whether dietary fructose intake was related to alterations in hippocampal volume and connectivity in humans. To examine if these associations were specific to fructose or were related to dietary sugars intake in general, we explored relationships between dietary intake of a ...[more]

PMID: 32224933

Similar Datasets

Project description:The role of nutrition and diet in the development of non-alcoholic fatty liver disease (NAFLD) is still not fully understood. In the present study, we determined if dietary pattern and markers of intestinal permeability differ between overweight children with and without NAFLD. In addition, in a feasibility study, we assessed the effect of a moderate dietary intervention only focusing on nutrients identified to differ between groups on markers of intestinal barrier function and health status. Anthropometric data, dietary intake, metabolic parameters, and markers of inflammation, as well as of intestinal permeability, were assessed in overweight children (n = 89, aged 5⁻9) and normal-weight healthy controls (n = 36, aged 5⁻9). Sixteen children suffered from early signs of NAFLD, e.g., steatosis grade 1 as determined by ultrasound. Twelve children showing early signs of NAFLD were enrolled in the intervention study (n = 6 intervention, n = 6 control). Body mass index (BMI), BMI standard deviation score (BMI-SDS), and waist circumference were significantly higher in NAFLD children than in overweight children without NAFLD. Levels of bacterial endotoxin, lipopolysaccharide-binding protein (LBP), and proinflammatory markers like interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) were also significantly higher in overweight children with NAFLD compared to those without. Total energy and carbohydrate intake were higher in NAFLD children than in those without. The higher carbohydrate intake mainly resulted from a higher total fructose and glucose intake derived from a significantly higher consumption of sugar-sweetened beverages. When counseling children with NAFLD regarding fructose intake (four times, 30⁻60 min within 1 year; one one-on-one counseling and three group counselings), neither alanine aminotransferase (ALT) nor aspartate aminotransferase (AST) activity in serum changed; however, diastolic blood pressure (p < 0.05) and bacterial endotoxin levels (p = 0.06) decreased markedly in the intervention group after one year. Similar changes were not found in uncounseled children. Our results suggest that a sugar-rich diet might contribute to the development of early stages of NAFLD in overweight children, and that moderate dietary counseling might improve the metabolic status of overweight children with NAFLD.

Project description:BackgroundWestern-style diets arouse neuroinflammation and impair emotional and cognitive behavior in humans and animals. Our previous study showed that a high-fructose diet caused the hippocampal neuroinflammatory response and neuronal loss in animals, but the underlying mechanisms remained elusive. Here, alterations in the gut microbiota and intestinal epithelial barrier were investigated as the causes of hippocampal neuroinflammation induced by high-fructose diet.ResultsA high-fructose diet caused the hippocampal neuroinflammatory response, reactive gliosis, and neuronal loss in C57BL/6N mice. Depletion of the gut microbiota using broad-spectrum antibiotics suppressed the hippocampal neuroinflammatory response in fructose-fed mice, but these animals still exhibited neuronal loss. Gut microbiota compositional alteration, short-chain fatty acids (SCFAs) reduction, intestinal epithelial barrier impairment, NOD-like receptor family pyrin domain-containing 6 (NLRP6) inflammasome dysfunction, high levels of serum endotoxin, and FITC-dextran were observed in fructose-fed mice. Of note, SCFAs, as well as pioglitazone (a selective peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist), shaped the gut microbiota and ameliorated intestinal epithelial barrier impairment and NLRP6 inflammasome dysfunction in fructose-fed mice. Moreover, SCFAs-mediated NLRP6 inflammasome activation was inhibited by histamine (a bacterial metabolite) in ex vivo colonic explants and suppressed in murine CT26 colon carcinoma cells transfected with NLRP6 siRNA. However, pioglitazone and GW9662 (a PPAR-γ antagonist) exerted no impact on SCFAs-mediated NLRP6 inflammasome activation in ex vivo colonic explants, suggesting that SCFAs may stimulate NLRP6 inflammasome independently of PPAR-γ activation. SCFAs and pioglitazone prevented fructose-induced hippocampal neuroinflammatory response and neuronal loss in mice. Additionally, SCFAs activated colonic NLRP6 inflammasome and increased DCX+ newborn neurons in the hippocampal DG of control mice.ConclusionsOur findings reveal that gut dysbiosis is a critical factor for a high-fructose diet-induced hippocampal neuroinflammation in C57BL/6N mice possibly mediated by impairing intestinal epithelial barrier. Mechanistically, the defective colonic NLRP6 inflammasome is responsible for intestinal epithelial barrier impairment. SCFAs can stimulate NLRP6 inflammasome and ameliorate the impairment of intestinal epithelial barrier, resulting in the protection against a high-fructose diet-induced hippocampal neuroinflammation and neuronal loss. This study addresses a gap in the understanding of neuronal injury associated with Western-style diets. A new intervention strategy for reducing the risk of neurodegenerative diseases through SCFAs supplementation or dietary fiber consumption is emphasized.

Project description:BackgroundFructose consumption is a potential risk factor for hyperuricemia because uric acid (UA) is a byproduct of fructose metabolism caused by the rapid consumption of adenosine triphosphate and accumulation of adenosine monophosphate (AMP) and other purine nucleotides. Additionally, a clinical experiment with four gout patients demonstrated that intravenous infusion of fructose increased the purine de novo synthesis rate, which implied fructose-induced hyperuricemia might be related to purine nucleotide synthesis. Moreover, the mechanistic (mammalian) target of rapamycin (mTOR) is a key protein both involved in fructose metabolism and purine de novo synthesis. The present study was conducted to elucidate how fructose influences mTOR and purine de novo synthesis in a hepatic cell line and livers of mice.Materials and methodsRNA-sequencing in NCTC 1469 cells treated with 0- and 25-mM fructose for 24 h and metabolomics analysis on the livers of mice fed with 0- and 30-g/kg fructose for 2 weeks were assessed. Gene and protein expression of phosphoribosyl pyrophosphate synthase (PRPSAP1), Glutamine PRPP aminotransferase (PPAT), adenyl succinate lyase (ADSL), adenyl succinate synthetase isozyme-1 (Adss1), inosine-5'-monophosphate dehydrogenase (IMPDH), and guanine monophosphate synthetase (GMPS) was measured. The location of PRPSAP1 and PPAT in the liver was assessed by an immunofluorescence assay.ResultsMetabolite profiling showed that the level of AMP, adenine, adenosine, hypoxanthine, and guanine was increased significantly. RNA-sequencing showed that gene expression of phosphoribosyl pyrophosphate synthase (PRPS2), phosphoribosyl glycinamide formyl transferase (GART), AICAR transformylase (ATIC), ADSL, Adss1, and IMPDH were raised, and gene expression of adenosine monophosphate deaminase 3 (AMPD3), adenosine deaminase (ADA), 5',3'-nucleotidase, cytosolic (NT5C), and xanthine oxidoreductase (XOR) was also increased significantly. Fructose increased the gene expression, protein expression, and fluorescence intensity of PRPSAP1 and PPAT in mice livers by increasing mTOR expression. Fructose increased the expression and activity of XOR, decreased the expression of uricase, and increased the serum level of UA.ConclusionThis study demonstrated that the increased purine de novo synthesis may be a crucial mechanism for fructose-induced hyperuricemia.

Dataset Information

Dietary Fructose Intake and Hippocampal Structure and Connectivity during Childhood.

Publications

Dietary Fructose Intake and Hippocampal Structure and Connectivity during Childhood.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets