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

Background/Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

[1]  I. Kavakli,et al.  Diurnal Changes in Capecitabine Clock-Controlled Metabolism Enzymes Are Responsible for Its Pharmacokinetics in Male Mice , 2023, Journal of biological rhythms.

[2]  Z. Younossi,et al.  Nonalcoholic Fatty Liver Disease: Disease Burden and Disease Awareness. , 2023, Clinics in liver disease.

[3]  Manuel Vargas-Vargas,et al.  Avocado oil alleviates non-alcoholic fatty liver disease by improving mitochondrial function, oxidative stress and inflammation in rats fed a high fat–High fructose diet , 2022, Frontiers in Pharmacology.

[4]  Wachirawadee Malakul,et al.  Naringin attenuates fructose-induced NAFLD progression in rats through reducing endogenous triglyceride synthesis and activating the Nrf2/HO-1 pathway , 2022, Frontiers in Pharmacology.

[5]  Sunhee Jung,et al.  Dietary Fructose and Fructose-Induced Pathologies. , 2022, Annual review of nutrition.

[6]  Tianlong Liu,et al.  Akkermansia muciniphila Colonization Alleviating High Fructose and Restraint Stress-Induced Jejunal Mucosal Barrier Disruption , 2022, Nutrients.

[7]  Yong Su,et al.  New Insights into the Diurnal Rhythmicity of Gut Microbiota and Its Crosstalk with Host Circadian Rhythm , 2022, Animals : an open access journal from MDPI.

[8]  G. Ji,et al.  The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease , 2021, Frontiers in Pharmacology.

[9]  Jiaqi Wang,et al.  Alkaline phosphatase attenuates LPS-induced liver injury by regulating the miR-146a-related inflammatory pathway. , 2021, International immunopharmacology.

[10]  P. Muriel,et al.  Fructose and the Liver , 2021, International journal of molecular sciences.

[11]  M. Jin,et al.  Intestinal Microbiota Mediates High-Fructose and High-Fat Diets to Induce Chronic Intestinal Inflammation , 2021, Frontiers in Cellular and Infection Microbiology.

[12]  B. Popkin,et al.  Towards unified and impactful policies to reduce ultra-processed food consumption and promote healthier eating. , 2021, The lancet. Diabetes & endocrinology.

[13]  W. Qi,et al.  High-Fructose Diet Increases Inflammatory Cytokines and Alters Gut Microbiota Composition in Rats , 2020, Mediators of inflammation.

[14]  J. Woo,et al.  Impact of the new definition of metabolic associated fatty liver disease on the epidemiology of the disease. , 2020, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[15]  P. Watkins,et al.  Glutamate dehydrogenase as a biomarker for mitotoxicity; insights from furosemide hepatotoxicity in the mouse , 2020, PloS one.

[16]  N. Miura,et al.  Chronotoxicity of Streptomycin-Induced Renal Injury in Mice. , 2020, Biological & pharmaceutical bulletin.

[17]  M. Cruz-López,et al.  High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymes , 2019, Molecular Biology Reports.

[18]  M. Brady,et al.  Dietary Fructose Consumption and Triple-Negative Breast Cancer Incidence , 2019, Front. Endocrinol..

[19]  W. Willett,et al.  Food in the Anthropocene: the EAT–Lancet Commission on healthy diets from sustainable food systems , 2019, The Lancet.

[20]  K. Seyssel,et al.  The extra-splanchnic fructose escape after ingestion of a fructose-glucose drink: An exploratory study in healthy humans using a dual fructose isotope method. , 2019, Clinical nutrition ESPEN.

[21]  M. Sakono,et al.  Daily Consumption of Bilberry ( Vaccinium myrtillus L.) Extracts Increases the Absorption Rate of Anthocyanins in Rats. , 2018, Journal of agricultural and food chemistry.

[22]  M. Do,et al.  High-Glucose or -Fructose Diet Cause Changes of the Gut Microbiota and Metabolic Disorders in Mice without Body Weight Change , 2018, Nutrients.

[23]  Tetsuya Yoshikawa,et al.  Diurnal Variation of Melatonin Concentration in the Cerebrospinal Fluid of Unanesthetized Microminipig. , 2018, In vivo.

[24]  L. Tappy Fructose-containing caloric sweeteners as a cause of obesity and metabolic disorders , 2018, Journal of Experimental Biology.

[25]  B. Brzozowski,et al.  The Role of Intestinal Alkaline Phosphatase in Inflammatory Disorders of Gastrointestinal Tract , 2017, Mediators of inflammation.

[26]  G. Matić,et al.  Fructose-enriched diet induces inflammation and reduces antioxidative defense in visceral adipose tissue of young female rats , 2017, European Journal of Nutrition.

[27]  S. Grundy Overnutrition, ectopic lipid and the metabolic syndrome , 2016, Journal of Investigative Medicine.

[28]  M. S. Malo,et al.  A High Level of Intestinal Alkaline Phosphatase Is Protective Against Type 2 Diabetes Mellitus Irrespective of Obesity , 2015, EBioMedicine.

[29]  H. Yki-Järvinen Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. , 2014, The lancet. Diabetes & endocrinology.

[30]  J. Millán,et al.  Intestinal alkaline phosphatase prevents metabolic syndrome in mice , 2013, Proceedings of the National Academy of Sciences.

[31]  A. Wakita,et al.  Serum alkaline phosphatase isoenzymes in SD rats detected by polyacrylamide-gel disk electrophoresis , 2012, Toxicology mechanisms and methods.

[32]  K. Chin,et al.  Survey of American food trends and the growing obesity epidemic , 2011, Nutrition research and practice.

[33]  Bevil R. Conway,et al.  Color Vision: Mice See Hue Too , 2007, Current Biology.

[34]  G. H. Jacobs,et al.  Emergence of Novel Color Vision in Mice Engineered to Express a Human Cone Photopigment , 2007, Science.

[35]  K. Tsutsumi,et al.  The relationship between lipoprotein lipase activity and respiratory quotient of rats in circadian rhythms. , 2002, Biological & pharmaceutical bulletin.

[36]  G. Cornelissen,et al.  Circadian rhythm of sister chromatid exchanges in human chromosomes. , 1995, In vivo.

[37]  S. Amagaya,et al.  Diurnal variations in blood chemical items in Sprague-Dawley rats. , 1995, Experimental animals.

[38]  H. Sakakibara,et al.  Novel Biomarker Establishment for Evaluation of Excessive Fructose Consumption Using a Rat Model , 2023, In Vivo.

[39]  Yusuke Suzuki,et al.  Specificity of transaminase activities in the prediction of drug-induced hepatotoxicity. , 2020, The Journal of toxicological sciences.

[40]  K. Shimoi,et al.  Dosage time affects alkylating agents induced micronuclei in mouse peripheral blood reticulocytes through the function of erythropoietin. , 2019, The Journal of toxicological sciences.

[41]  N. Miura,et al.  Multidirectional analyses of hepatic chronotoxicity induced by cadmium in mice. , 2017, The Journal of toxicological sciences.

[42]  K. Kimura,et al.  Whey Protein-hydrolyzed Peptides Diminish Hepatic Lipid Levels in Rats Consuming High-sucrose Diets , 2016 .

[43]  S. Zucoloto,et al.  Fructose and NAFLD: metabolic implications and models of induction in rats. , 2011, Acta cirurgica brasileira.

[44]  K. Shimoi,et al.  Effects of animal care procedures on plasma corticosterone levels in group-housed mice during the nocturnal active phase. , 2010, Experimental animals.

[45]  Health Beneficial Effects of Food Factors Can Be Applicable to Humans? Guest Editor: Kazuki Kanazawa Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors , 2022 .