PMID: 

Microbiome. 2019 Jun 29 ;7(1):98. Epub 2019 Jun 29. PMID: 31255176

Abstract Title: 

Dietary fructose-induced gut dysbiosis promotes mouse hippocampal neuroinflammation: a benefit of short-chain fatty acids.

Abstract: 

BACKGROUND: Western-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.RESULTS: A 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-γactivation. SCFAs and pioglitazone prevented fructose-induced hippocampal neuroinflammatory response and neuronal loss in mice. Additionally, SCFAs activated colonic NLRP6 inflammasome and increased DCXnewborn neurons in the hippocampal DG of control mice.CONCLUSIONS: Our 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.

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PMID: 

J Nutr Biochem. 2019 Jun ;68:42-50. Epub 2019 Mar 26. PMID: 31030166

Abstract Title: 

High-fructose drinks affect microRNAs expression differently in lean and obese mice.

Abstract: 

High fructose intake from soft drinks and sweets is assumed to have a negative impact on human health. Yet in spite of intensive research, the molecular mechanisms of these effects have not been fully elucidated yet, for example, the effect of high fructose intake could be different in normal and obese individuals. Four groups of mice were used in this study: control groups of lean mice and mice with obesity induced by a high-fat diet, then both of these groups with or without fructose administration in drinks. In plasma of each group, triacylglycerol, cholesterol, free fatty acids, alanine aminotransferase, insulin and adiponectin were measured. The expression levels of selected microRNAs (miRNAs) in plasma, the liver, white adipose tissue, brown adipose tissue and subcutaneous adipose tissue were quantified. In both lean and obese mice, high fructose intake increased cholesterol amount in the liver, up-regulated hepatic miR-27a, down-regulated miR-33a in white adipose tissue and increased plasmatic level of miR-21. The effect of high fructose intake on other miRNAs in the liver, plasma and adipose tissues differed in normal and obese mice. Fructose intake led to hepatic hypercholesterolemia and aberrant expression of several miRNAs participating in lipid metabolism, adipocytes differentiation and nonalcoholic fatty liver disease promotion. The effect of fructose on miRNAs expression differed in normal and obese mice. Nevertheless, plasmatic miR-21, which was induced by fructose in both lean and obese mice, may be considered as a potential biomarker of excessive fructose intake.

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PMID: 

Nutrition. 2019 Mar 28 ;65:103-112. Epub 2019 Mar 28. PMID: 31079017

Abstract Title: 

Beneficial effects of intermittent fasting on steatosis and inflammation of the liver in mice fed a high-fat or a high-fructose diet.

Abstract: 

OBJECTIVE: Intermittent fasting (IF) is a nutritional intervention with significant metabolic effects on the liver that are not yet fully understood. The aim of this study was to investigate the effects of IF on body mass, lipid profile, glucose metabolism, liver lipogenesis,β-oxidation, and inflammation.METHODS: We used cellular and molecular techniques to investigate the effects of IF on 3-mo-old male C57 BL/6 mice that were fed control (10% kcal fat), high-fat (HF; 50% kcal fat), or high-fructose (HFr; 50% kcal fructose) diets for 8 wk. Half of the animals were submitted to IF (1 d fed, 1 d fast) for an additional 4 wk.RESULTS: Although food intake on the fed day did not differ between the groups, mice in the HF and HFr groups showed diminished body mass, total cholesterol, and triacylglycerol levels. Also, plasma adiponectin increased in the HFr group and leptin decreased in the HF mice. Oral glucose tolerance test and insulin were ameliorated by IF, regardless of the diet consumed (HF or HFr), and decreased hepatic lipogenesis and increasedβ-oxidation markers, resulting in a reduction of the hepatic steatosis and inflammation.CONCLUSIONS: There were beneficial effects of IF even with the continuity of the obesogenic diet and proinflammatory diet in mice. It is recommended that based on the beneficial effects of IF on glucose and liver metabolism and inflammation that IF be a coadjutant factor in the treatment of hepatic metabolic issues and steatosis.

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PMID: 

J Physiol. 2019 Jul ;597(14):3561-3571. Epub 2019 Jun 9. PMID: 31116420

Abstract Title: 

Health outcomes of a high fructose intake: the importance of physical activity.

Abstract: 

Fructose metabolism is generally held to occur essentially in cells of the small bowel, the liver, and the kidneys expressing fructolytic enzymes (fructokinase, aldolase B and a triokinase). In these cells, fructose uptake and fructolysis are unregulated processes, resulting in the generation of intracellular triose phosphates proportionate to fructose intake. Triose phosphates are then processed into lactate, glucose and fatty acids to serve as metabolic substrates in other cells of the body. With small oral loads, fructose is mainly metabolized in the small bowel, while with larger loads fructose reaches the portal circulation and is largely extracted by the liver. A small portion, however, escapes liver extraction and is metabolized either in the kidneys or in other tissues through yet unspecified pathways. In sedentary subjects, consumption of a fructose-rich diet for several days stimulates hepatic de novo lipogenesis, increases intrahepatic fat and blood triglyceride concentrations, and impairs insulin effects on hepatic glucose production. All these effects can be prevented when high fructose intake is associated with increased levels of physical activity. There is also evidence that, during exercise, fructose carbons are efficiently transferred to skeletal muscle as glucose and lactate to be used for energy production. Glucose and lactate formed from fructose can also contribute to the re-synthesis of muscle glycogen after exercise. We therefore propose that the deleterious health effects of fructose are tightly related to an imbalance between fructose energy intake on one hand, and whole-body energy output related to a low physical activity on the other hand.

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PMID: 

Phytomedicine. 2019 Jun 28 ;63:153002. Epub 2019 Jun 28. PMID: 31301539

Abstract Title: 

Boswellic extracts and 11-keto-ß-boswellic acids prevent type 1 and type 2 diabetes mellitus by suppressing the expression of proinflammatory cytokines.

Abstract: 

BACKGROUND: Type 1 diabetes is an autoimmune disease directed to the pancreatic islets where inflammation leads to the death of insulin-producingß cells and insulin deficiency. Type 2 diabetes, which is closely related to overweight, is characterized by insulin resistance. In both cases, proinflammatory cytokines play an important role by causing insulitis and insulin resistance. The gum resin of Boswellia species and its pharmacologicallyactive compounds, including 11-keto-ß-boswellic acids have been shown to suppress the expression of proinflammatory cytokines in various immune-competent cells.PURPOSE: To review the present evidence of the therapeutic effects of boswellic extracts (BE) and/or 11-keto-ß-boswellic acids in the prevention/treatment of diabetes mellitus and to provide comprehensive insights into the underlying molecular mechanisms.METHODS: This review considers all available informations from preclinical and clinical studies concerning BEs, 11-keto-ß-boswellic acids, proinflammatory cytokines and diabetes mellitus collected via electronic search (PubMed) and related publications of the author.RESULTS: Type 1 diabetes: Studies in mice with autoimmune diabetes revealed that in the model of multiple injections of low doses of streptozotocin (MLD-STZ), an extract of the gum resin of Boswellia serrata and 11-keto-ß-boswellic acid (KBA) suppressed the increase in proinflammatory cytokines in the blood, infiltration of lymphocytes into pancreatic islets and increase in blood glucose. In a second model, i.e. the nonobese diabetic (NOD) mouse, KBA prevented the infiltration of lymphocytes into pancreatic islets. Regarding the clinical effects, a case report provided evidence that BE suppressed the blood levels of tyrosine phosphatase antibody (IA-A), a marker for insulitis, in a patient with late-onset autoimmune diabetes of the adult (LADA). Type 2 diabetes: In a preclinical study in rats where obesity was alimentary induced, the administration of BE significantly reduced food intake, overweight, proinflammatory cytokines such as interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) and ameliorated the parameters of glucose and lipid metabolism. Similar results were obtained in a second animal study, where type 2 diabetes was induced by a combination of a high-fat/high-fructose diet and a single dose of streptozotocin. Two clinical trials with patients with type 2 diabetes receiving the resin of Boswellia serrata demonstrated improvement in the blood glucose, HbAand lipid parameters.CONCLUSION: Preclinical and clinical data suggest that BE and/or 11-keto-ß-boswellic acids by inhibiting the expression of proinflammatory cytokines from immune-competent cells, may prevent insulitis and insulin resistance in type 1 and type 2 diabetes, respectively, and therefore may be an option in the treatment/prevention of type 1 and type 2 diabetes. It is hypothesized that molecularly, BE and 11-keto-ß-boswellic acids act via interference with the IκB kinase/Nuclear Transcription Factor-κB (IKK/NF-κB) signaling pathway through inhibition of the phosphorylation activity of IKK. However, further investigations and well-designed clinical studies are required.

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Gratitude Is Good For Your Health – https://weil.ws/2KMomK4 

PMID: 

BMC Nephrol. 2018 11 8 ;19(1):315. Epub 2018 Nov 8. PMID: 30409184

Abstract Title: 

Fructose increases risk for kidney stones: potential role in metabolic syndrome and heat stress.

Abstract: 

BACKGROUND: Fructose intake, mainly as table sugar or high fructose corn syrup, has increased in recent decades and is associated with increased risk for kidney stones. We hypothesized that fructose intake alters serum and urinary components involved in stone formation.METHODS: We analyzed a previously published randomized controlled study that included 33 healthy male adults (40-65 years of age) who ingested 200 g of fructose (supplied in a 2-L volume of 10% fructose in water) daily for 2 weeks. Participants were evaluated at the Unit of Nephrology of the Mateo Orfila Hospital in Menorca. Changes in serum levels of magnesium, calcium, uric acid, phosphorus, vitamin D, andintact PTH levels were evaluated. Urine magnesium, calcium, uric acid, phosphorus, citrate, oxalate, sodium, potassium, as well as urinary pH, were measured.RESULTS: Ingestion of fructose was associated with an increased serum level of uric acid (p 

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PMID: 

Diabetes Metab Syndr Obes. 2019 ;12:821-826. Epub 2019 May 27. PMID: 31213868

Abstract Title: 

The negative and detrimental effects of high fructose on the liver, with special reference to metabolic disorders.

Abstract: 

The increased consumption of fructose in the average diet through sweeteners such as high-fructose corn syrup (HFCS) and sucrose has resulted in negative outcomes in society through producing a considerable economic and medical burden on our healthcare system. Ingestion of fructose chronically has contributed to multiple health consequences, such as insulin resistance, obesity, liver disorders, and diabetes. Fructose metabolism starts with fructose phosphorylation by fructose kinase in the liver, and this process is not feedback regulated. Therefore, ingestion of high fructose can deplete ATP, increase uric acid production, and increase nucleotide turnover. This review focuses the discussion on the hepatic manifestations of high fructose-implicated liver metabolic disorders such as insulin resistance, obesity due to enhanced lipogenesis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and type 2 diabetes. The detrimental effects of high fructose on the liver, contributed potentially by microbiome and leptin, were also discussed. The authors believe that, together with diet management, further studies focusing on disrupting or blocking fructose metabolism in the liver may help with designing novel strategies for prevention and treatment of fructose-induced chronic liver metabolic diseases.

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PMID: 

Science. 2019 03 22 ;363(6433):1345-1349. PMID: 30898933

Abstract Title: 

High-fructose corn syrup enhances intestinal tumor growth in mice.

Abstract: 

Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated with obesity and with an increased risk of colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. We investigated the effects of daily oral administration of HFCS in adenomatous polyposis coli (APC) mutant mice, which are predisposed to develop intestinal tumors. The HFCS-treated mice showed a substantial increase in tumor size and tumor grade in the absence of obesity and metabolic syndrome. HFCS increased the concentrations of fructose and glucose in the intestinal lumen and serum, respectively, and the tumors transported both sugars. Within the tumors, fructose was converted to fructose-1-phosphate, leading to activation of glycolysis and increased synthesis of fatty acids that support tumor growth. These mouse studies support the hypothesis that the combination of dietary glucose and fructose, even at a moderate dose, can enhance tumorigenesis.

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PMID: 

Circulation. 2019 Apr 30 ;139(18):2113-2125. PMID: 30882235

Abstract Title: 

Long-Term Consumption of Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Mortality in US Adults.

Abstract: 

BACKGROUND: Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with risk of mortality is of public health interest.METHODS: We examined associations between consumption of SSBs and ASBs with risk of total and cause-specific mortality among 37 716 men from the Health Professional's Follow-up study (from 1986 to 2014) and 80 647 women from the Nurses' Health study (from 1980 to 2014) who were free from chronic diseases at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals.RESULTS: We documented 36 436 deaths (7896 cardiovascular disease [CVD] and 12 380 cancer deaths) during 3 415 564 person-years of follow-up. After adjusting for major diet and lifestyle factors, consumption of SSBs was associated with a higher risk of total mortality; pooled hazard ratios (95% confidence intervals) across categories (

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