Sour Taste SNP KCNJ2-rs236514 and Differences in Nutrient Intakes and Metabolic Health Markers in the Elderly

Single nucleotide polymorphisms (SNPs) in taste receptors influence dietary choices that contribute to health and quality of life. Individual differences in sour taste perception and preference have been linked to heritable genetics, yet the impact of sour taste receptor SNPs on sour taste is under-researched, and studies on sour taste SNP associations to diet and health are lacking. Therefore, this study explored the relationships between the sour taste SNP KCNJ2-rs236514 and estimated macronutrient, vitamin and mineral intakes, and markers of metabolic health. Associations were explored in 523 participants aged 65 years and older with data analysed using standard least squares and nominal logistic regression modelling with post hoc student's t-tests and Tukey's HSD. Associations were found between the presence of the KCNJ2-rs236514 variant allele (A) and lower intakes of energy, total fat, monounsaturated fat and saturated fat. The lower fat intakes were significant in female carriers of the variant allele (A), along with lower water intake. Lower retinol, riboflavin, folate, calcium and sodium intakes were found in the KCNJ2-A allele carriers. In females, the variant allele was associated with lower sodium intake before and after Bonferroni adjustment. Higher body mass index, waist and waist-to-hip ratio measures were found in males carrying the variant allele. Lower levels of liver function biomarkers were associated with the presence of the KCNJ2-A allele. Overall and in males, the variant's association to lower gamma-glutamyl transferase (GGT) levels remained significant after Bonferroni adjustments. These novel findings suggest the sour taste SNP, KCNJ2-rs236514, may be modifying macronutrient, vitamin and mineral intakes, and markers of metabolic health. Research on the extra-oral functions of this SNP may improve health outcomes for those with overweight, obesity and liver disease.

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11βHSD1 Inhibition with AZD4017 Improves Lipid Profiles and Lean Muscle Mass in Idiopathic Intracranial Hypertension

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa766 ◽

2020 ◽

Vol 106 (1) ◽

pp. 174-187

Author(s):

Rowan S Hardy ◽

Hannah Botfield ◽

Keira Markey ◽

James L Mitchell ◽

Zerin Alimajstorovic ◽

...

Keyword(s):

Intracranial Hypertension ◽

Muscle Mass ◽

Idiopathic Intracranial Hypertension ◽

Hepatic Function ◽

Lipid Profiles ◽

Gamma Glutamyl Transferase ◽

Peripheral Tissues ◽

Lean Muscle Mass ◽

Glutamyl Transferase ◽

The Impact

Abstract Background The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH). Methods We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry. Results Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased high-density lipoprotein [HDL] and cholesterol/HDL ratio), markers of hepatic function (decreased alkaline phosphatase and gamma-glutamyl transferase), and increased lean muscle mass (1.8%, P < .001). No changes in body mass index, fat mass, and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass. Conclusions These beneficial metabolic changes represent a reduction in risk factors associated with raised intracranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia.

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Roles of Moringa oleifera Leaf Extract in Improving the Impact of High Dietary Intake of Monosodium Glutamate-Induced Liver Toxicity, Oxidative Stress, Genotoxicity, DNA Damage, and PCNA Alterations in Male Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/4501097 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Tarfa Albrahim ◽

Manal Abdulaziz Binobead

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Leaf Extract ◽

Liver Toxicity ◽

Monosodium Glutamate ◽

Male Rats ◽

Control Group ◽

Gamma Glutamyl Transferase ◽

Glutamyl Transferase ◽

The Impact

It is common for food to be made more palatable through the use of the flavour enhancer monosodium glutamate, also known as vetsin powder. The purpose of the study described in this paper was to explore how vetsin-induced hepatic toxicity, DNA fragmentation, damage, and oxidative stress modifications could be mitigated with moringa leaf extract (MLE). To that end, 40 male rats were separated into four groups: normal control, positive control or MLE, vetsin, and vetsin combined with MLE. Results indicated that, compared to the control group, the levels of serum alanine aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), liver malondialdehyde (MDA), DNA damage, injury, PCNA, and P53 expressions were significantly enhanced by the administration of vetsin (P<0.05). However, the vetsin group had significantly reduced levels of albumin, globulin, total protein, liver glutathione (GSH), superoxide dismutase enzyme (SOD), catalase, and glutathione S-transferase (GST) enzyme activities (P<0.05) by comparison to control. Meanwhile, modifications in liver functions, oxidative stress, DNA damage, liver injury, and PCNA expression were alleviated when vetsin was administered alongside MLE. The authors conclude that vetsin may have many side effects and that MLE can ameliorate biochemical changes, oxidative stress, hepatic injury, PCNA, and P53 alterations induced by vetsin administration.

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Relationship between Alcohol Consumption and Impaired Liver Function

JURNAL INFO KESEHATAN ◽

10.31965/infokes.vol18.iss2.474 ◽

2020 ◽

Vol 18 (2) ◽

pp. 163-170

Author(s):

Agustina W. Djuma ◽

Novian A. Yudhaswara ◽

Suzanne Patricia Dardeau

Keyword(s):

Alcohol Consumption ◽

Liver Function ◽

Gamma Glutamyl Transferase ◽

Research Subjects ◽

Impaired Liver Function ◽

Cross Sectional ◽

Impaired Liver ◽

Glutamyl Transferase ◽

The Impact ◽

The Relationship

East Nusa Tenggara is a province of high alcohol abuse in Indonesia. Ngada Regency has a prevalence of 38.8%. The high prevalence is inseparable from traditional factors and socio-cultural norms which strongly influence the habit of consuming alcohol, the cold temperature in this area further strengthens this habit. The impact of alcohol consumption is the emergence of various types of diseases, one of which is impaired liver function such as alcoholic liver disease. The objective of this study is to determine the relationship between alcohol consumption and impaired liver function in communities in Bajawa and Golewa Districts, Ngada Regency. This research method is an observational analytic with cross-sectional design. The research subjects were 55 people who consumed alcohol in Golewa and Bajawa Districts, who had met the inclusion criteria. Alcohol consumption was measured by the AUDIT (The Alcohol Use Disorders Identification Test) questionnaire, while the parameter for liver disorders was the level of Gamma Glutamyl Transferase (GGT). The prevalence of liver dysfunction based on GGT examination was 15%. Meanwhile, the relationship between alcohol consumption and impaired liver function was tested with the Spearman correlation with α 0.05, the correlation value was p = 0.413, which means it has a moderate or significant, not too strong relationship. It is recommended that the people of Ngada Regency reduce alcohol consumption so that it can reduce the risk of impaired liver function.

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Impact of the cardio-hepatic syndrome on outcomes after transcatheter mitral valve edge-to-edge repair

European Heart Journal ◽

10.1093/eurheartj/ehab724.2217 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

L Stolz ◽

M Orban ◽

N Karam ◽

E Lubos ◽

M Wild ◽

...

Keyword(s):

Liver Function ◽

Cox Regression ◽

Cox Model ◽

Hepatic Function ◽

Gamma Glutamyl Transferase ◽

Prognostic Impact ◽

Laboratory Parameters ◽

Glutamyl Transferase ◽

The Impact

Abstract Background The prognostic value of impaired liver function in the presence of moderate-to-severe and severe mitral regurgitation (MR), also called cardio-hepatic syndrome (CHS), for outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) has not been studied yet. Purpose In this work, we aimed at identifying the prognostic impact of the CHS on two-year all-cause mortality in patients undergoing TEER compared to established risk factors. Furthermore, we evaluated the change in hepatic function after TEER. Methods Hepatic function was assessed by laboratory parameters of liver function (bilirubin, gamma glutamyl transferase [GGT], alkaline phosphatase [AP], aspartate and alanine aminotransferase [AST and ALT]). We defined CHS as elevation of at least two out of three laboratory parameters of hepatic cholestasis (bilirubin, GGT, AP). The impact of CHS on two-year mortality was evaluated using a proportional hazards Cox model. The change in hepatic function after TEER was evaluated by repeat laboratory testing at follow-up. Results We included 1083 patients who underwent TEER for highly symptomatic primary or secondary MR at four high volume academic European centers between 2008 and 2019. In 66.4% of patients, we observed elevated levels of either bilirubin, GGT or AP. CHS was present in 23% of patients and showed strong association with a reduced two-year survival (52.9% vs. 87.0% in patients without CHS, p<0.01). In a multivariate Cox regression model, CHS was identified as a strong and independent predictor of increased two-year mortality (hazard ratio 1.49, p=0.03). In patients with successful MR reduction ≤2+ (90.7% of patients), parameters of hepatic function significantly improved from baseline to follow-up (−0.2 mg/dl for bilirubin; −21 U/l for GGT, respectively, p<0.01), while they did not in case of residual postprocedural MR >2+. Conclusions CHS can be observed in up to 25% of patients undergoing TEER and is associated with impaired two-year survival rates. Successful TEER is associated with decreased levels of hepatic enzymes at follow-up evaluation. FUNDunding Acknowledgement Type of funding sources: None. Cardio-hepatic syndrome TEER

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Gamma-glutamyl Transferase Levels are Associated with the Occurrence of Post-stroke Cognitive Impairment: A Multicenter Cohort Study

10.21203/rs.3.rs-789716/v1 ◽

2021 ◽

Author(s):

Siqi Li ◽

Xiaoling Liao ◽

Yuesong Pan ◽

Xianglong Xiang ◽

Yumei Zhang

Keyword(s):

Cohort Study ◽

Cognitive Impairment ◽

Gamma Glutamyl Transferase ◽

Multicenter Cohort Study ◽

Gamma Glutamyl ◽

Post Stroke ◽

Multicenter Cohort ◽

Glutamyl Transferase ◽

The Impact

Abstract Background: Gamma-glutamyl transferase (GGT) can maintain the physiological concentration of glutathione in cells, and protect them from oxidative stress-induced damage. However, its role in post-stroke cognitive impairment (PSCI) remains unknown. Here, we explored the impact of serum biomarker-GGT on PSCI. Methods: We conducted a prospective, multicenter cohort study. 1, 957 participants who suffered a stroke and measured baseline GGT were enrolled from the Impairment of Cognition and Sleep (ICONS) study of the China National Stroke Registry-3 (CNSR-3). They were categorized into four groups according to the quartiles of baseline GGT levels. Cognitive function was assessed by using the Montreal Cognitive Assessment (MoCA) approach. The multiple logistic regression models were performed to evaluate the relationship between GGT and PSCI at 3 months follow-up.Results: Among 1,957 participants, 671 (34.29%) patients suffered PSCI at 3 months follow-up. The highest GGT level quartile group exhibited a lower risk of PSCI in the fully adjusted model [OR (95% CI): 0.69 (0.50-0.96)], relative to the lowest group. Moreover, incorporation of GGT to the conventional model resulted in a slight improvement in PSCI outcomes after 3 months (NRI: 12.00%; IDI: 0.30%).Conclusions: Our findings demonstrated that serum GGT level was inversely associated with the risk of PSCI, with extremely low levels acting as a risk factor for PSCI.

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Role of percutaneous liver biopsy in infantile cholestasis: cohort from Arabs

BMC Gastroenterology ◽

10.1186/s12876-021-01699-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Amna Basheer M. Ahmed ◽

Musa Ahmad Fagih ◽

Muhammed Salman Bashir ◽

Abdulrahman Abdullah Al-Hussaini

Keyword(s):

Liver Biopsy ◽

Diagnostic Yield ◽

Molecular Testing ◽

Gamma Glutamyl Transferase ◽

High Gamma ◽

Infantile Cholestasis ◽

Glutamyl Transferase ◽

Gene Panels ◽

The Impact

Abstract Background Investigators from different parts of the world are calling for a re-evaluation of the role of liver biopsy (LB) in the evaluation of infantile cholestasis (IC), especially in the light of emerging non-invasive diagnostic technologies. Therefore, this retrospective single-center study was conducted to determine the impact of LB on the diagnosis and management of IC in a cohort from Arabs. Methods From 2007 until 2019, 533 cases of IC were referred for evaluation. All infants who underwent LB were included in the study. We categorized the yield of LB into: (1) defined specific diagnosis; (2) excluded an important diagnosis. A single pathologist reviewed and made the histology report. Results 122 LB specimens met the inclusion criteria. The main indication for LB was a high suspicion of biliary atresia (BA) [high gamma-glutamyl transferase (GGT) cholestasis and pale stool] in 46 cases (37.8%). Liver biopsy had sensitivity of 86.4%, specificity (66.7%), PPV (70.4%), NPV (84.2%) in diagnosing BA. LB had a direct impact on clinical management in 52 cases (42.6%): (1) The true diagnosis was suggested by LB in 36 cases; (2) LB excluded BA and avoided intraoperative cholangiogram in 16 cases with high suspicion of BA. Among the 76 cases with low suspicion of BA, LB suggested the true diagnosis or helped to initiate specific management in 8 cases only (10.5%). In contrast, molecular testing confirmed the diagnosis in 48 (63%). Conclusion LB continues to be an important tool in the workup of cases with a high suspicion of BA. The low yield of LB in cases with low suspicion of BA calls for a re-evaluation of its role in these cases in whom early incorporation of cholestasis sequencing gene panels can have a better diagnostic yield.

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Decrease in rat taste receptor cell intracellular pH is the proximate stimulus in sour taste transduction

AJP Cell Physiology ◽

10.1152/ajpcell.2001.281.3.c1005 ◽

2001 ◽

Vol 281 (3) ◽

pp. C1005-C1013 ◽

Cited By ~ 109

Author(s):

Vijay Lyall ◽

Rammy I. Alam ◽

Duy Q. Phan ◽

Glenn L. Ereso ◽

Tam-Hao T. Phan ◽

...

Keyword(s):

Intracellular Ph ◽

Plasma Membranes ◽

Taste Receptor ◽

Taste Perception ◽

Sour Taste ◽

Taste Transduction ◽

Taste Reception ◽

Small Change ◽

Strong Acids ◽

Paracellular Shunt

Taste receptor cells (TRCs) respond to acid stimulation, initiating perception of sour taste. Paradoxically, the pH of weak acidic stimuli correlates poorly with the perception of their sourness. A fundamental issue surrounding sour taste reception is the identity of the sour stimulus. We tested the hypothesis that acids induce sour taste perception by penetrating plasma membranes as H+ ions or as undissociated molecules and decreasing the intracellular pH (pHi) of TRCs. Our data suggest that taste nerve responses to weak acids (acetic acid and CO2) are independent of stimulus pH but strongly correlate with the intracellular acidification of polarized TRCs. Taste nerve responses to CO2 were voltage sensitive and were blocked with MK-417, a specific blocker of carbonic anhydrase. Strong acids (HCl) decrease pHi in a subset of TRCs that contain a pathway for H+ entry. Both the apical membrane and the paracellular shunt pathway restrict H+ entry such that a large decrease in apical pH is translated into a relatively small change in TRC pHi within the physiological range. We conclude that a decrease in TRC pHi is the proximate stimulus in rat sour taste transduction.

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Post-hoc analysis of a randomized controlled trial on the impact of pre-transplant use of probiotics on outcomes after liver transplantation

Scientific Reports ◽

10.1038/s41598-020-76994-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

M. Grąt ◽

K. Grąt ◽

M. Krawczyk ◽

Z. Lewandowski ◽

M. Krasnodębski ◽

...

Keyword(s):

Liver Transplantation ◽

Graft Survival ◽

Controlled Trial ◽

Long Term Results ◽

Gamma Glutamyl Transferase ◽

Long Term Effects ◽

Post Transplant ◽

Glutamyl Transferase ◽

The Impact

AbstractPerioperative use of probiotics serves as efficient prophylaxis against postoperative infections after liver transplantation, yet data on long-term effects of pre-transplant probiotic intake is lacking. The aim of this study was to assess the effects of pre-transplant probiotic administration on long-term results of liver transplantation. This was secondary analysis of a randomized trial. Patients were randomized to receive either 4-strain probiotic or placebo before liver transplantation. Five year graft survival was set as the primary end-point. Secondary end-points comprised serum bilirubin and C-reactive protein (CRP) concentration, international normalized ratio (INR), serum transaminases and gamma-glutamyl transferase (GGT) activity. Study group comprised 44 patients, of whom 21 received probiotics and 23 received placebo with 5-year graft survival of 81.0% and 87.0%, respectively (p = 0.591). Patients in the probiotic arm exhibited lower INR (p = 0.001) and CRP (p = 0.030) over the first 6 post-transplant months. In the absence of hepatitis B or C virus infection, pre-transplant administration of probiotics also reduced aspartate transaminase activity (p = 0.032). In the intervention arm, patients receiving probiotics for under and over 30 days had 5-year graft survival rates of 100% and 66.7%, respectively (p = 0.061). Duration of probiotic intake > 30 days was additionally associated with increased INR (p = 0.031), GGT (p = 0.032) and a tendency towards increased bilirubin (p = 0.074) over first 6 post-transplant months. Pre-transplant administration of probiotics has mild positive influence on 6-month allograft function, yet should not exceed 30 days due to potential negative effects on long-term outcomes. (ClinicalTrials.gov Identifier: NCT01735591).

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Diethylnitrosamine aggravates cadmium-induced hepatorenal oxidative damage in prepubertal rats

Toxicology and Industrial Health ◽

10.1177/0748233719863287 ◽

2019 ◽

Vol 35 (8) ◽

pp. 537-547 ◽

Cited By ~ 1

Author(s):

Solomon E Owumi ◽

Uche J Dim ◽

Eseroghene S Najophe

Keyword(s):

Oxidative Damage ◽

Dietary Exposure ◽

Gamma Glutamyl Transferase ◽

Exposure Group ◽

Simultaneous Exposure ◽

Liver And Kidney ◽

Antioxidant Defense Systems ◽

Prepubertal Rats ◽

Glutamyl Transferase ◽

The Impact

The adverse health consequences of environmental, occupational, and dietary exposure to either diethylnitrosamine (DEN) or cadmium (Cd) have been widely investigated. However, because most environmental exposures to xenobiotics do not occur in isolation but in mixtures, the effects of simultaneous exposure to both DEN and Cd on hepatorenal function deserves investigation. The present study investigated the impact of 7 days oral co-exposure to 10 mg/kg body weight (b.w.) of DEN and 5 mg/kg b.w. of Cd on biomarkers of hepatic and renal functions, antioxidant defense systems, and oxidative stress indices in the liver and kidney of prepubertal rats. The results showed that the significant ( p < 0.05) increases in the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, urea, and creatinine following separate administration of DEN and Cd to rats were further increased in the co-exposure group. Moreover, marked decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase as well as glutathione levels following individual administration of DEN and Cd to rats were exacerbated in the co-exposure group. Further, the marked increase in the lipid peroxidation level and the histopathological lesions in the liver and kidney of rats treated with DEN or Cd alone were intensified in the co-exposure group These findings indicate that co-exposure to DEN and Cd elicited more severe hepatic and renal oxidative damage in the rats, thus suggesting a greater risk to humans who are co-exposed to them.

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Ameliorative effect of gallic acid on methotrexate-induced hepatotoxicity and nephrotoxicity in rat

Journal of Xenobiotics ◽

10.4081/xeno.2016.6092 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Ebenezer Tunde Olayinka ◽

Ayokanmi Ore ◽

Oluwatobi Adewumi Adeyemo ◽

Olaniyi Solomon Ola

Keyword(s):

Gallic Acid ◽

Gamma Glutamyl Transferase ◽

Glutathione S Transferase ◽

Group I ◽

Malondialdehyde Content ◽

Ameliorative Effect ◽

Male Wistar Rats ◽

Enzymic Antioxidants ◽

Glutamyl Transferase ◽

The Impact

We investigated the protective effect of gallic acid (GA) against methotrexate (MTX)-induced hepatotoxicity and nephrotoxicity. Male Wistar rats were randomized into five groups (n = 6/group): I, control; II, MTX-treated for seven days; III, pre-treated with GA for seven days, followed by MTX for seven days; IV, co-treated with MTX and GA for seven days and V, GA for seven days. MTX caused a significant increase (P<0.05) in plasma biomarkers of nephrotoxicity (urea, creatinine) and hepatotoxicity (Bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase) when compared with control. Furthermore, MTX caused a significant decrease in the activities of hepatic enzymic antioxidants (superoxide dismutase, catalase, glutathione S-transferase) and nonenzymic antioxidants (Vitamin C and glutathione), followed by a significant increase in hepatic malondialdehyde content. However, pretreatment and co-treatment with gallic acid ameliorated the MTX-induced biochemical changes observed. Taken together, GA protected against MTX-induced hepatotoxicity and nephrotoxicity in rats, by reducing the impact of oxidative damage to tissues.

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