Bioactive dipeptides mitigate high-fat and high-fructose corn syrup diet-induced metabolic-associated fatty liver disease via upregulation of Nrf2/HO-1 expressions in C57BL/6J mice.

Metabolic-associated fatty liver disease (MAFLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), is a common liver disease characterized by an abnormal buildup of fat in liver. This study aimed to investigate whether bioactive dipeptides mitigate high-fat and high-fructose corn syrup diet (HFFD)-induced MAFLD in C57BL/6J mice. Sixty male C57BL/6J mice were randomly divided into six groups. The naïve group (untreated) was fed a standard chow diet and other groups were fed with HFFD along with vehicle and bioactive dipeptides treatment throughout experiment period. The control group received vehicle, YF10 and YF50 groups received Tyr-Phe, 10 and 50 mg/kg/day, FY10 and FY50 groups received Phe-Tyr, 10 and 50 mg/kg/day. At the end of experiment, body weight was recorded, and glucose homeostasis was assessed. Mice were sacrificed and blood samples were collected to measure biochemical parameters. Further, liver, visceral fat pads, and other organs were acutely dissected, weighed, and processed. Histopathological and immunohistochemical changes were analyzed. Long-term HFFD feeding resulted in elevated body weight gain, liver weight, visceral adiposity, liver injury, fasting hyperglycemia, hyperinsulinemia, and hyperlipidemia. It also increased severe hepatic steatosis, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and lipid peroxidation. However, bioactive dipeptides dose-dependently alleviated these complications which are associated with MAFLD by modulating adipokines secretion and antioxidant defense system via upregulation of Nrf2/HO-1 expressions. This study highlights potential of bioactive dipeptides as a promising approach for prevention and/or treatment of MAFLD induced by HFFD, providing novel insights into alternative therapeutic strategies.

Integrated omics analysis for characterization of the contribution of high fructose corn syrup to non-alcoholic fatty liver disease in obesity.

BACKGROUND: High-Fructose Corn Syrup (HFCS), a sweetener rich in glucose and fructose, is nowadays widely used in beverages and processed foods; its consumption has been correlated to the emergence and progression of Non-Alcoholic Fatty Liver Disease (NAFLD). Nevertheless, the molecular mechanisms by which HFCS impacts hepatic metabolism remain scarce, especially in the context of obesity. Besides, the majority of current studies focuses either on the detrimental role of fructose in hepatic steatosis or compare separately the additive impact of fructose versus glucose in high fat diet-induced NAFLD. AIM: By engaging combined omics approaches, we sought to characterize the role of HFCS in obesity-associated NAFLD and reveal molecular processes, which mediate the exaggeration of steatosis under these conditions. METHODS: Herein, C57BL/6 mice were fed a normal-fat-diet (ND), a high-fat-diet (HFD) or a HFD supplemented with HFCS (HFD-HFCS) and upon examination of their metabolic and NAFLD phenotype, proteomic, lipidomic and metabolomic analyses were conducted to identify HFCS-related molecular alterations of the hepatic metabolic landscape in obesity. RESULTS: Although HFD and HFD-HFCS mice displayed comparable obesity, HFD-HFCS mice showed aggravation of hepatic steatosis, as analysis of the lipid droplet area in liver sections revealed (12,15 % of total section area in HFD vs 22,35 % in HFD-HFCS), increased NAFLD activity score (3,29 in HFD vs 4,86 in HFD-HFCS) and deteriorated hepatic insulin resistance, as compared to the HFD mice. Besides, the hepatic proteome of HFD-HFCS mice was characterized by a marked upregulation of 5 core proteins implicated in de novo lipogenesis (DNL), while an increased phosphatidyl-cholines(PC)/phosphatidyl-ethanolamines(PE) ratio (2.01 in HFD vs 3.04 in HFD-HFCS) was observed in the livers of HFD-HFCS versus HFD mice. Integrated analysis of the omics datasets indicated that Tricarboxylic Acid (TCA) cycle overactivation is likely contributing towards the intensification of steatosis during HFD-HFCS-induced NAFLD. CONCLUSION: Our results imply that HFCS significantly contributes to steatosis aggravation during obesity-related NAFLD, likely deriving from DNL upregulation, accompanied by TCA cycle overactivation and deteriorated hepatic insulin resistance.

Dietary Fructose and Fructose-Induced Pathologies.

The consumption of fructose as sugar and high-fructose corn syrup has markedly increased during the past several decades. This trend coincides with the exponential rise of metabolic diseases, including obesity, nonalcoholic fatty liver disease, cardiovascular disease, and diabetes. While the biochemical pathways of fructose metabolism were elucidated in the early 1990s, organismal-level fructose metabolism and its whole-body pathophysiological impacts have been only recently investigated. In this review, we discuss the history of fructose consumption, biochemical and molecular pathways involved in fructose metabolism in different organs and gut microbiota, the role of fructose in the pathogenesis of metabolic diseases, and the remaining questions to treat such diseases.

High-fructose diet during puberty alters the sperm parameters, testosterone concentration, and histopathology of testes and epididymis in adult Wistar rats.

The consumption of fructose has increased in children and adolescents and is partially responsible for the high incidence of metabolic diseases. The lifestyle during postnatal development can result in altered metabolic programming, thereby impairing the reproductive system and fertility during adulthood. Therefore, the aim of this study was to evaluate the effect of a high-fructose diet in the male reproductive system of pubertal and adult rats. Male Wistar rats (30 d old) were assigned to four different groups: Fr30, which received fructose (20%) in water for 30 d and were euthanized at postnatal day (PND) 60; Re-Fr30, which received fructose (20%) for 30 d and were euthanized at PND 120; and two control groups C30 and Re-C30, which received water ad libitum and were euthanized at PND 60 and 120, respectively. Fructose induced an increase in abnormal seminiferous tubules with epithelial vacuoles, degeneration, and immature cells in the lumen. Moreover, Fr30 rats showed altered spermatogenesis and daily sperm production (DSP), as well as increased serum testosterone concentrations. After discontinuing high-fructose consumption, DSP and sperm number decreased significantly. We observed tissue remodeling in the epididymis, with a reduction in stromal and epithelial compartments that might have influenced sperm motility. Therefore, we concluded that fructose intake in peripubertal rats led to changes in the reproductive system observed both during puberty and adulthood.

"Sweet death": Fructose as a metabolic toxin that targets the gut-liver axis.

Glucose and fructose are closely related simple sugars, but fructose has been associated more closely with metabolic disease. Until the 1960s, the major dietary source of fructose was fruit, but subsequently, high-fructose corn syrup (HFCS) became a dominant component of the Western diet. The exponential increase in HFCS consumption correlates with the increased incidence of obesity and type 2 diabetes mellitus, but the mechanistic link between these metabolic diseases and fructose remains tenuous. Although dietary fructose was thought to be metabolized exclusively in the liver, evidence has emerged that it is also metabolized in the small intestine and leads to intestinal epithelial barrier deterioration. Along with the clinical manifestations of hereditary fructose intolerance, these findings suggest that, along with the direct effect of fructose on liver metabolism, the gut-liver axis plays a key role in fructose metabolism and pathology. Here, we summarize recent studies on fructose biology and pathology and discuss new opportunities for prevention and treatment of diseases associated with high-fructose consumption.

Dietary fructose improves intestinal cell survival and nutrient absorption.

Fructose consumption is linked to the rising incidence of obesity and cancer, which are two of the leading causes of morbidity and mortality globally1,2. Dietary fructose metabolism begins at the epithelium of the small intestine, where fructose is transported by glucose transporter type 5 (GLUT5; encoded by SLC2A5) and phosphorylated by ketohexokinase to form fructose 1-phosphate, which accumulates to high levels in the cell3,4. Although this pathway has been implicated in obesity and tumour promotion, the exact mechanism that drives these pathologies in the intestine remains unclear. Here we show that dietary fructose improves the survival of intestinal cells and increases intestinal villus length in several mouse models. The increase in villus length expands the surface area of the gut and increases nutrient absorption and adiposity in mice that are fed a high-fat diet. In hypoxic intestinal cells, fructose 1-phosphate inhibits the M2 isoform of pyruvate kinase to promote cell survival5-7. Genetic ablation of ketohexokinase or stimulation of pyruvate kinase prevents villus elongation and abolishes the nutrient absorption and tumour growth that are induced by feeding mice with high-fructose corn syrup. The ability of fructose to promote cell survival through an allosteric metabolite thus provides additional insights into the excess adiposity generated by a Western diet, and a compelling explanation for the promotion of tumour growth by high-fructose corn syrup.

Lactose-reduced infant formula with added corn syrup solids is associated with a distinct gut microbiota in Hispanic infants.

Infant formula feeding, compared with human milk, has been associated with development of a distinct infant gut microbiome, but no previous study has examined effects of formula with added sugars. This work examined differences in gut microbiota among 91 Hispanic infants who consumed human milk [at breast (BB) vs. pumped in bottle (BP)] and 2 kinds of infant formula [(traditional lactose-based (TF) vs. lactose-reduced with added sugar (ASF)]. At 1 and 6 months, infant stool was collected to characterize gut microbiota. At 6 months, mothers completed 24-hour dietary recalls and questionnaires to determine infant consumption of human milk (BB vs. BP) or formula (TF vs. ASF). Linear regression models were used to determine associations of milk consumption type and microbial features at 6 months. Infants in the formula groups exhibited a significantly more 'mature' microbiome than infants in the human milk groups with the most pronounced differences observed between the ASF vs. BB groups. In the ASF group, we observed reduced log-normalized abundance of Bifidobacteriaceae (TF-BB Mean Difference = -0.71, ASF-BB Mean Difference = -1.10), and increased abundance of Lachnospiraceae (TF-BB Mean Difference = +0.89, ASF-BB Mean Difference = +1.20). We also observed a higher Community Phenotype Index of propionate, most likely produced by Lachnospiraceae, in the ASF group (TF-BB Mean Difference = +0.27, ASF-BB Mean Difference = +0.36). This study provides the first evidence that consumption of infant formula with added sugar may have a stronger association than birth delivery mode, infant caloric intake, and maternal BMI on the infant's microbiome at 6 months of age.

The effect of corn syrup and whey on the conversion process of CO to ethanol using Clostridium ljungdahlii.

CO is one of the toxic components of syngas, which is the major source of air pollution. Syngas fermentation technology has the ability to convert toxic gases into valuable biofuels, such as ethanol. Fermentative ethanol production is an important method that can be used to promote environmental protection. CO can be converted into ethanol, via the Wood-Ljungdahl pathway, using Clostridium ljungdahlii. The components of the growing medium--especially the trace-element solution and yeast extract--are the main reasons for the high costs associated with this process, however, and this especially impacts scaled-up operations. In this study, cheaper substitutes for these components were used in order to determine their effect on ethanol production. The study comprised three main parts--the optimization of CO concentration, and the substitution of corn syrup and whey powder in the process. The optimum volume of CO for ethanol production was found to be 10 mL. Corn syrup can be used instead of trace-element solution, but the use of yeast extract with the corn syrup was determined to be essential. Up to 1.4 g/L ethanol production was observed with the addition of 15 mL corn syrup. Whey powder had the advantage of being usable without yeast extract, with up to 2.5 g/L ethanol being produced from a 30-g/L concentration. The main finding was that either corn syrup or whey powder can be used as substitutes for expensive basal-medium components.

Determining the contribution of a high-fructose corn syrup formulation to hepatic glycogen synthesis during ad-libitum feeding in mice.

Excessive sugar intake including high-fructose corn syrup (HFCS) is implicated in the rise of obesity, insulin resistance and non-alcoholic fatty liver disease. Liver glycogen synthesis is influenced by both fructose and insulin signaling. Therefore, the effect of HFCS on hepatic glycogenesis was evaluated in mice feeding ad-libitum. Using deuterated water: the fraction of glycogen derived from triose-P sources, Krebs cycle substrates, and direct pathway + cycling, was measured in 9 normal-chow fed mice (NC) and 12 mice fed normal chow plus a 55% fructose/45% glucose mix in the drinking water at 30% w/v (HFCS-55). This was enriched with [U-13C]fructose or [U-13C]glucose to determine the contribution of each to glycogenesis. For NC, direct pathway + cycling, Krebs cycle, and triose-P sources accounted for 66 ± 0.7%, 23 ± 0.8% and 11 ± 0.4% of glycogen synthesis, respectively. HFCS-55 mice had similar direct pathway + cycling (64 ± 1%) but lower Krebs cycle (12 ± 1%, p < 0.001) and higher triose-P contributions (24 ± 1%, p < 0.001). HFCS-55-fructose contributed 17 ± 1% via triose-P and 2 ± 0% via Krebs cycle. HFCS-55-glucose contributed 16 ± 3% via direct pathway and 1 ± 0% via Krebs cycle. In conclusion, HFCS-55 supplementation resulted in similar hepatic glycogen deposition rates. Indirect pathway contributions shifted from Krebs cycle to Triose-P sources reflecting HFCS-55-fructose utilization, while HFCS-55-glucose was incorporated almost exclusively by the direct pathway.

Updates on inulinases: Structural aspects and biotechnological applications.

Inulinases are inulin catalyzing enzymes which belongs to glycoside hydrolases (GH) family 32. Bacteria, fungi and yeasts are the potential sources of inulinases. In the present biotechnological era, inulinases are gaining considerable attention, due to their wide range of applications which includes the production of high fructose syrup, fructooligosaccharides and many other important metabolites like bioethanol, organic acids, single cell oil, 2,3-butanediol, single cell proteins, etc. These applications of inulinases have attracted the researchers world-wide to understand the inulin-inulinase interactions for polyfructan hydrolysis. To understand these interactions, the information on structural organization of inulinases is very important which is scarce in literature. The current review highlights the structural and functional properties of inulinases, and difference in their structural organization. The biotechnological potential of inulinases for the production of different bio-products from inulin/inulin-rich raw materials using different bioprocessing strategies has also been elaborated.

High-level expression of Thermobifida fusca glucose isomerase for high fructose corn syrup biosynthesis.

Glucose isomerase (GIase), an efficient enzyme in the isomerization of d-glucose to d-fructose, has been widely used in food processing. In this study, an efficient expression system for a Thermobifida fusca GIase (GIaseTfus) in Escherichia coli was firstly designed via a two-stage feeding strategy for improving expression level. The cultivation strategy was performed at an exponential feeding rate during the pre-induction phase, followed by a gradient-decreasing feeding rate at the induction phase in a 3-L fermenter. During this process, the effect of induction conditions and the complex nitrogen supplementation in feeding solutions on GIaseTfus production were investigated and optimized. Under the optimal conditions, the yield of GIaseTfus reached 124.1 U/mL, which is the highest expression level of GIase by recombinant E. coli reported to date. Additionally, the obtained GIaseTfus was performed to produce high fructose corn syrup (HFCS) with conversion approacing 55 % from glucose (45 %, w/v) to fructose. According to the molecular dynamic simulation, a number of hydrogen bonds existed in the enzyme-substrate complex could stablilize the transient states, and a appreciate reaction distance of M1 catalytic site and oxygen atom of glucose make the reaction proceed easily, thus resulting in the efficient biosynthesis of HFCS. The function of GIaseTfus renders it a valuable catalyst for HFCS-55 (containing 55 % d-fructose) manufacturing, the most favorable industrial product of HFCS. The efficient expression of GIaseTfus and its efficient HFCS production lays the foundation for its proming industrial application.

Enhancement of 1,3-propanediol production from industrial by-product by Lactobacillus reuteri CH53.

BACKGROUND: 1,3-propanediol (1,3-PDO) is the most widely studied value-added product that can be produced by feeding glycerol to bacteria, including Lactobacillus sp. However, previous research reported that L. reuteri only produced small amounts and had low productivity of 1,3-PDO. It is urgent to develop procedures that improve the production and productivity of 1,3-PDO. RESULTS: We identified a novel L. reuteri CH53 isolate that efficiently converted glycerol into 1,3-PDO, and performed batch co-fermentation with glycerol and glucose to evaluate its production of 1,3-PDO and other products. We optimized the fermentation conditions and nitrogen sources to increase the productivity. Fed-batch fermentation using corn steep liquor (CSL) as a replacement for beef extract led to 1,3-PDO production (68.32 ± 0.84 g/L) and productivity (1.27 ± 0.02 g/L/h) at optimized conditions (unaerated and 100 rpm). When CSL was used as an alternative nitrogen source, the activity of the vitamin B12-dependent glycerol dehydratase (dhaB) and 1,3-propanediol oxidoreductase (dhaT) increased. Also, the productivity and yield of 1,3-PDO increased as well. These results showed the highest productivity in Lactobacillus species. In addition, hurdle to 1,3-PDO production in this strain were identified via analysis of the half-maximal inhibitory concentration for growth (IC50) of numerous substrates and metabolites. CONCLUSIONS: We used CSL as a low-cost nitrogen source to replace beef extract for 1,3-PDO production in L. reuteri CH53. These cells efficiently utilized crude glycerol and CSL to produce 1,3-PDO. This strain has great promise for the production of 1,3-PDO because it is generally recognized as safe (GRAS) and non-pathogenic. Also, this strain has high productivity and high conversion yield.

Potential of an Interorgan Network Mediated by Toxic Advanced Glycation End-Products in a Rat Model.

Excessive intake of glucose and fructose in beverages and foods containing high-fructose corn syrup (HFCS) plays a significant role in the progression of lifestyle-related diseases (LSRD). Glyceraldehyde-derived advanced glycation end-products (AGEs), which have been designated as toxic AGEs (TAGE), are involved in LSRD progression. Understanding of the mechanisms underlying the effects of TAGE on gene expression in the kidneys remains limited. In this study, DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were used to investigate whether HFCS-consuming Wister rats generated increased intracellular serum TAGE levels, as well as the potential role of TAGE in liver and kidney dysfunction. HFCS consumption resulted in significant accumulation of TAGE in the serum and liver of rats, and induced changes in gene expression in the kidneys without TAGE accumulation or upregulation of receptor for AGEs (RAGE) upregulation. Changes in specific gene expression profiles in the kidney were more correlated with TAGE levels in the liver tissue than in the serum. These findings suggest a direct or indirect interaction may be present between the liver and kidneys that does not involve serum TAGE or RAGE. The involvement of internal signal transduction factors such as exosomes or cytokines without IL-1ß and TNF-α is suggested to contribute to the observed changes in kidney gene expression.

Consumption of fructose rich industrialized beverages in patients with biopsy-proven non-alcoholic fatty liver disease: a cross-sectional study

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and liver fibrosis. Recently, consumption of high fructose corn syrup (HFCS) has been associated with NAFLD development. OBJECTIVE: The aim of this study was to investigate the relationship between consumption of HFCS and NAFLD associated metabolic factors and disease progression. METHODS: This cross-sectional study included 51 patients with biopsy-proven NAFLD who underwent biochemical tests, anthropometrical assessment and full-day dietary evaluation including industrialized beverages quantification. RESULTS: Individuals were 80% female, with 54 ± 12 years old, 96% with central obesity, 75% with insulin resistance or diabetes mellitus and were separated according to industrialized beverage intake: < 7 and ≥ 7 coups/week (i.e., daily). Daily consumption of HFCS was associated with obesity (P = 0.04), hypertriglyceridemia (P = 0.05), higher serum triglycerides (P = 0.03) and VLDL (P = 0.01). There was a significant correlation (R = 0.29; P = 0.04) between consumption of industrialized beverages and increased serum triglycerides. We found no association between daily HFCS intake and NASH diagnosis or presence of fibrosis. CONCLUSION: Excessive consumption of HFCS in industrialized beverages was associated with obesity, hypertriglyceridemia and high levels of blood triglycerides in patients with NAFLD

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Evidence for Toxic Advanced Glycation End-Products Generated in the Normal Rat Liver.

Glucose/fructose in beverages/foods containing high-fructose corn syrup (HFCS) are metabolized to glyceraldehyde (GA) in the liver. We previously reported that GA-derived advanced glycation end-products (toxic AGEs, TAGE) are generated and may induce the onset/progression of non-alcoholic fatty liver disease (NAFLD). We revealed that the generation of TAGE in the liver and serum TAGE levels were higher in NAFLD patients than in healthy humans. Although we propose the intracellular generation of TAGE in the normal liver, there is currently no evidence to support this, and the levels of TAGE produced have not yet been measured. In the present study, male Wister/ST rats that drank normal water or 10% HFCS 55 (HFCS beverage) were maintained for 13 weeks, and serum TAGE levels and intracellular TAGE levels in the liver were analyzed. Rats in the HFCS group drank 127.4 mL of the HFCS beverage each day. Serum TAGE levels and intracellular TAGE levels in the liver both increased in the HFCS group. A positive correlation was observed between intracellular TAGE levels in the liver and serum TAGE levels. On the other hand, in male Wister/ST rats that drank Lactobacillus beverage for 12 weeks-a commercial drink that contains glucose, fructose, and sucrose- no increases were observed in intracellular TAGE or serum TAGE levels. Intracellular TAGE were generated in the normal rat liver, and their production was promoted by HFCS, which may increase the risk of NAFLD.

High Fructose Intake and Adipogenesis.

In modern societies, high fructose intake from sugar-sweetened beverages has contributed to obesity development. In the diet, sucrose and high fructose corn syrup are the main sources of fructose and can be metabolized in the intestine and transported into the systemic circulation. The liver can metabolize around 70% of fructose intake, while the remaining is metabolized by other tissues. Several tissues including adipose tissue express the main fructose transporter GLUT5. In vivo, chronic fructose intake promotes white adipose tissue accumulation through activating adipogenesis. In vitro experiments have also demonstrated that fructose alone induces adipogenesis by several mechanisms, including (1) triglycerides and very-low-density lipoprotein (VLDL) production by fructose metabolism, (2) the stimulation of glucocorticoid activation by increasing 11ß-HSD1 activity, and (3) the promotion of reactive oxygen species (ROS) production through uric acid, NOX and XOR expression, mTORC1 signaling and Ang II induction. Moreover, it has been observed that fructose induces adipogenesis through increased ACE2 expression, which promotes high Ang-(1-7) levels, and through the inhibition of the thermogenic program by regulating Sirt1 and UCP1. Finally, microRNAs may also be involved in regulating adipogenesis in high fructose intake conditions. In this paper, we propose further directions for research in fructose participation in adipogenesis.

A novel thermostable and efficient Class II glucose isomerase from the thermophilic Caldicoprobacter algeriensis: Biochemical characterization, molecular investigation, and application in High Fructose Syrup production.

A novel glucose isomerase gene from the thermophilic Caldicoprobacter algeriensis, encoding a polypeptide of 438 residues, was identified, cloned and successfully expressed in E. coli. The purified enzyme (GICA) was a homotetramer of about 200 kDa displaying the highest activity at pH 7.0 and 90 °C and retaining 97% of its maximum activity at pH 6.5. The enzyme showed an excellent thermostability with a half-life of 6 min at 100 °C. Interestingly, GICA had a very high affinity of 40 mM and catalytic efficiency of 194 min-1 mM-1 toward d-glucose at 90 °C. A maximum of 54.7% d-glucose to d-fructose conversion was achieved by GICA at 85 °C making it an attractive candidate for HFCS-55 production. The primary sequence inspection and molecular modeling studies revealed that the thermal stability of GICA could be attributed to the presence of extra charged residues at the surface like E108 and Q408 increasing surface charge interactions. Moreover, a serine at position 56 near to P58 could establish hydrogen bond strengthening the dimer attachment. The high catalytic efficiency and affinity of GICA could be ascribed to the presence of amino acid like E108 and K62 that created more charges around the catalytic site entry.

Whole cell immobilization of refractory glucose isomerase using tris(hydroxymethyl)phosphine as crosslinker for preparation of high fructose corn syrup at elevated temperature.

Glucose isomerase (GI) responsible for catalyzing the isomerization from d-glucose to d-fructose, was an important enzyme for producing high fructose corn syrup (HFCS). In a quest to prepare HFCS at elevated temperature and facilitate enzymatic recovery, an effective procedure for whole cell immobilization of refractory Thermus oshimai glucose isomerase (ToGI) onto Celite 545 using tris(hydroxymethyl)phosphine (THP) as crosslinker was established. The immobilized biocatalyst showed an activity of approximate 127.3 U/(g·immobilized product) via optimization in terms of cells loading, crosslinker concentration and crosslinking time. The pH optimum of the immobilized biocatalyst was displaced from pH 8.0 of native enzyme to neutral pH 7.0. Compared with conventional glutaraldehyde (GLU)-immobilized cells, it possessed the enhanced thermostability with 70.1% residual activity retaining after incubation at 90°C for 72 h. Moreover, the THP-immobilized biocatalyst exhibited superior operational stability, in which it retained 85.8% of initial activity after 15 batches of bioconversion at 85°C. This study paved a way for reducing catalysis cost for upscale preparation of HFCS with higher d-fructose concentration.

Prenatal and Early Life Fructose, Fructose-Containing Beverages, and Midchildhood Asthma.

RATIONALE: Cross-sectional studies have linked intake of high-fructose corn syrup-sweetened beverages with asthma in schoolchildren. OBJECTIVES: To examine associations of maternal prenatal and early childhood intake of sugar-sweetened beverages and fructose with current asthma in midchildhood (median age, 7.7 yr). METHODS: We assessed maternal pregnancy (first- and second-trimester average) and child (median age, 3.3 yr) intake of sugar-sweetened beverages and total fructose using food frequency questionnaires in 1,068 mother-child pairs from Project Viva, a prospective prebirth cohort. In a multivariable analysis, we examined associations of quartiles of maternal and child sugar-sweetened beverage, juice, and total fructose intake with child current asthma in midchildhood, assessed by questionnaire as ever having doctor-diagnosed asthma plus taking asthma medications or reporting wheezing in the past 12 months. RESULTS: Higher maternal pregnancy sugar-sweetened beverage consumption (mean, 0.6 servings/d; range, 0-5) was associated with younger maternal age, nonwhite race/ethnicity, lower education and income, and higher prepregnancy body mass index. Adjusting for prepregnancy body mass index and other covariates, comparing quartile 4 with quartile 1, higher maternal pregnancy intake of sugar-sweetened beverages (odds ratio, 1.70; 95% confidence interval, 1.08-2.67) and total fructose (odds ratio, 1.58; 95% confidence interval, 0.98-2.53) were associated with greater odds of midchildhood current asthma (prevalence, 19%). Higher early childhood fructose intake (quartile 4 vs. quartile 1) was also associated with midchildhood current asthma in models adjusted for maternal sugar-sweetened beverages (odds ratio, 1.79; 95% confidence interval, 1.07-2.97) and after additional adjustment for midchildhood body mass index z-score (odds ratio, 1.77; 95% confidence interval, 1.06-2.95). CONCLUSIONS: Higher sugar-sweetened beverage and fructose intake during pregnancy and in early childhood was associated with childhood asthma development independent of adiposity.

Suppression of Ghrelin Exacerbates HFCS-Induced Adiposity and Insulin Resistance.

High fructose corn syrup (HFCS) is widely used as sweetener in processed foods and soft drinks in the United States, largely substituting sucrose (SUC). The orexigenic hormone ghrelin promotes obesity and insulin resistance; ghrelin responds differently to HFCS and SUC ingestion. Here we investigated the roles of ghrelin in HFCS- and SUC-induced adiposity and insulin resistance. To mimic soft drinks, 10-week-old male wild-type (WT) and ghrelin knockout (Ghrelin-/-) mice were subjected to ad lib. regular chow diet supplemented with either water (RD), 8% HFCS (HFCS), or 10% sucrose (SUC). We found that SUC-feeding induced more robust increases in body weight and body fat than HFCS-feeding. Comparing to SUC-fed mice, HFCS-fed mice showed lower body weight but higher circulating glucose and insulin levels. Interestingly, we also found that ghrelin deletion exacerbates HFCS-induced adiposity and inflammation in adipose tissues, as well as whole-body insulin resistance. Our findings suggest that HFCS and SUC have differential effects on lipid metabolism: while sucrose promotes obesogenesis, HFCS primarily enhances inflammation and insulin resistance, and ghrelin confers protective effects for these metabolic dysfunctions.