2011 Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

«The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stress the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.»

2012 Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects

«Significant reductions were observed in body weight (−8.04 ± 2.31 kg), body mass index (−2.92 ± 0.85 kg/m²), and percent body fat (−4.44% ± 2.00%), as well as a small decrease in heart rate (−2.56 ± 2.85 beats per minute), but with no significant changes to diet over the course of the study. Importantly, the decreases occurred when subjects were taking GCA. Body mass index for six subjects shifted from preobesity to the normal weight range (<25.00 kg/m²).»

2017 The Effects of Ginger on Fasting Blood Sugar, Hemoglobin A1c, and Lipid Profiles in Patients with Type 2 Diabetes

Data from 45 patients were analyzed (23 patients in the ginger group and 22 patients in the control group) at the end of the study. Ginger consumption significantly reduced serum levels of fasting blood glucose (-26.30 ± 35.27 vs. 11.91 ± 38.58 mg/dl; P = 0.001) and hemoglobin A1C (-0.38 ± 0.35 vs. 0.22 ± 0.29 %; P < 0.0001) compared to the placebo group. Ginger consumption also reduced the ratio of LDL-C/HDL-C (2.64 ± 0.85 vs. 2.35 ± 0.8; P = 0.009). However, there was no significant change in serum concentration of triglycerides, total cholesterol, LDL-C, and HDL-C due to the ginger supplements.

1999 Molecular genetic basis of Gilbert's syndrome.

«Gilbert's syndrome, an hereditary, chronic, mild, unconjugated hyperbilirubinaemia resulting from impaired hepatic bilirubin clearance and otherwise normal liver function, is arguably the most common syndrome known in humans. Recent molecular genetic studies have determined that the clinical phenotype can be described by a dinucleotide polymorphism in the TATA box promoter of the bilirubin uridine diphosphate-glucuronosyltransferase (UGT-1A1) gene, most frequently (TA)7TAA, affecting up to 36% of Africans, but only 3% of Asians. However, a second common heterozygous mutation in the coding exon 1 of the UGT-1A1 gene (G71R) can also cause the Gilbert's phenotype in Japanese and Asians. The clinical phenotype may not be apparent as frequently as the determined genotype, due to environmental factors such as alcohol-induced hepatic bilirubin glucuronidation, reducing serum bilirubin levels and causing a latent condition. Gilbert's disease is a contributory factor of prolonged neonatal jaundice in breast-fed infants and may precipitate jaundice when coinherited with other disorders of haem metabolism. The genetic variation described as Gilbert's syndrome may lead to pharmacological variation in drug glucuronidation and unexpected toxicity from therapeutic agents.»

2004 Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine.

"The contents of glucose, glycated protein, glycosylated haemoglobin and fructosamine were significantly lowered by taurine treatment to high fructose rats. Taurine prevented in vitro glycation and the accumulation of AGEs. Furthermore, taurine enhanced glucose utilization in the rat diaphragm. This effect was additive to that of insulin and did not interfere with the action of insulin."

2006 Challenging sleep in aging: the effects of 200 mg of caffeine during the evening in young and middle-aged moderate caffeine consumers.

«The aim of this study was to evaluate the effects of a 200-mg administration of caffeine on polysomnographic sleep variables and quantitative sleep electroencephalography (EEG) in 12 young (20-30 years) and 12 middle-aged (40-60 years) moderate caffeine consumers (one to three cups of coffee per day). All subjects were submitted to both a caffeine (200 mg) and placebo (lactose) condition in a double-blind cross-over design. The conditions were separated by 1 week. Compared with the placebo condition, the evening ingestion of caffeine lengthened sleep latency, reduced sleep efficiency, and decreased sleep duration and amount of stage 2 sleep in both age groups. Caffeine also reduced spectral power in delta frequencies in frontal, central and parietal brain areas, but not in prefrontal (PF) and occipital regions. Moreover, caffeine increased spectral power in beta frequencies in frontal and central brain areas in both age groups. A suppression of spectral power in the PF area in low delta frequencies (0.5-1.00 Hz) and a rise in spectral power in the parietal region in high alpha (10.00-12.00 Hz) and beta frequencies (17.00-21.00, 23.00-25.00, 27.00-29.00 Hz) occurred solely in middle-aged subjects. No such changes were noticeable in young subjects. Generally, caffeine produced similar effects in young and middle-aged subjects. Only a few frequency bins showed more effects of caffeine in middle-aged subjects compared with young subjects. Furthermore, sleep EEG results do not entirely support the hypothesis that caffeine fully mimics the effects of a reduction of homeostatic sleep propensity when following a normal sleep-wake cycle.»

2006 UGT1A1 promoter polymorphism as a predisposing factor of hyperbilirubinaemia in neonates with acute pyelonephritis.

«We describe 4 jaundice neonates with acute pyelonephritis of whom family history was positive for or pointed to Gilbert's syndrome (GS). Uridine diphosphate glucuronosyltransferase 1A1 (UGT-1A1), (TA)7 polymorphism, associated with GS was found in these neonates. We suggest that extended (TA)7 promoter, acting as a predisposing factor, contributes substantially to hyperbilirubinaemia seen in a number of neonates with urinary tract infections (UTI).»

2013 Development of icterus gravis in a preterm infant with G71R UGT1A1 polymorphism.

«CONCLUSION: We speculated that this preterm infant with carrying the G71R polymorphism reduced UGT1A1 activity and developed severe jaundice that was likely triggered by factors such as breast feeding and medications. The polymorphism appears at some frequency among VLBWIs, which would necessitate adequate care of severe jaundice even after the acute phase.»

2014 Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia.

Adequate calorie intake would lead to the sufficient expression of UGT1A1 in the small intestine to reduce serum bilirubin levels. Supplemental treatment of newborns with glucose solution can be a convenient and efficient method to treat neonatal jaundice while allowing continuous breastfeeding.

2015 Expanding roles for AMPK in skeletal muscle plasticity.

, regular moderate-intensity exercise induces favorable changes in
glucose intolerance and decreases mean plasma glucose levels in type 2 diabetic patients through increased muscle
glucose disposal

2015 The evaluation of inflammatory and oxidative stress biomarkers on coffee-diabetes association: results from the 10-year follow-up of the ATTICA Stu...

«During follow-up, 191 incident cases of diabetes were documented (incidence 13.4% in men and 12.4% in women). After various adjustments, individuals who consumed ⩾250 ml of coffee (≈1.5cup) had 54% lower odds of developing diabetes (95% confidence interval: 0.24, 0.90), as compared with abstainers. A dose-response linear trend between coffee drinking and diabetes incidence was also observed (P for trend=0.017). When controlling for several oxidative stress and inflammatory biomarkers, the inverse association between habitual coffee drinking and diabetes was found to be mediated by serum amyloid-A levels.»

«This work highlights the significance of long-term habitual coffee drinking against diabetes onset. The anti-inflammatory effect of several coffee components may be responsible for this protection.»

«Caffeine has been also found to stimulate pancreatic
insulin secretion and CGA is believed to act as a potent inhibitor of
glucose-6-phosphatase, which releases glucose to circulation, and, when abnormal, disturbs normoglycaemia. Both caffeine and CGA
decrease glucose gastric absorption, modulating GIP and GLP-1 secretion.»

«CGA has been shown to inhibit the activation of NF-κb in cultured cells.»

2016 Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the UDP-glucuronosyltransferase 1A1 Gene.

«The total bilirubin value of a male infant was 385 μmol/l on day 5. Liver function test results were normal and there was no evidence of sepsis and no hemolysis reaction. Phototherapy was administered and on day 8 the patient's total bilirubin level was 255 μmol/l. Intermittent episodes of hyperbilirubinemia occurred without phototherapy, with the total bilirubin level reaching 335 μmol/l on day 19. A 3-day regimen of phenobarbital was administered and on day 24 his total bilirubin level was 180 μmol/l. The patient was discharged. At the age of 2 months, the total bilirubin value was 27 μmol/l. His direct bilirubin value was <15% of total bilirubin in every determination. A family study of the UDP-glucuronosyltransferase(UGT)1A1 gene showed that the infant carries a homozygous mutation at nucleotide -3279 plus compound heterozygous mutations at nucleotides 782 and 1091. The mutation at nucleotide 782 is a novel finding. Gilbert's syndrome was diagnosed.»

2016 Features of an altered AMPK metabolic pathway in Gilbert's Syndrome, and its role in metabolic health.

«Energy metabolism, involving the ATP-dependent AMPK-PgC-Ppar pathway impacts metabolic health immensely, in that its impairment can lead to obesity, giving rise to disease. Based on observations that individuals with Gilbert's syndrome (GS; UGT1A1(*)28 promoter mutation) are generally lighter, leaner and healthier than controls, specific inter-group differences in the AMPK pathway regulation were explored. Therefore, a case-control study involving 120 fasted, healthy, age- and gender matched subjects with/without GS, was conducted. By utilising intra-cellular flow cytometry (next to assessing AMPKα1 gene expression), levels of functioning proteins (phospho-AMPK α1/α2, PgC 1 α, Ppar α and γ) were measured in PBMCs (peripheral blood mononucleated cells). In GS individuals, rates of phospho-AMPK α1/α2, -Ppar α/γ and of PgC 1α were significantly higher, attesting to a boosted fasting response in this condition. In line with this finding, AMPKα1 gene expression was equal between the groups, possibly stressing the post-translational importance of boosted fasting effects in GS. In reflection of an apparently improved health status, GS individuals had significantly lower BMI, glucose, insulin, C-peptide and triglyceride levels. Herewith, we propose a new theory to explain why individuals having GS are leaner and healthier, and are therefore less likely to contract metabolic diseases or die prematurely thereof.»

2017 The Association between Prolonged Jaundice and UGT1A1 Gene Polymorphism (G71R) in Gilbert's Syndrome.

«RESULTS: Overall, 84% and 64% of subjects in the study and control groups were male, respectively. The distribution of Gilbert genotype was not significantly different between the two groups (p=0.772). There was a correlation between prolonged jaundice in males and UGT1A1 G71R polymorphism (p =0.03). In the study group, 5(5.7%) subjects were homozygous (for A/A), 73 (83.9%) were heterozygous (for A/G), and 9(10.3%) were normal (for G/G). In the control group, 3(3.7%) participants were homozygous (A/A), 68(84%) were heterozygous (A/G) and 10 (12.3%) were normal (G/G).

CONCLUSION: There was no association between prolonged jaundice and G71R polymorphism, even though a relationship was revealed between male gender and the mentioned polymorphism.»

2018 Bilirubin acts as a multipotent guardian of cardiovascular integrity: more than just a radical idea.

«Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert's syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid/protein modifications, and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion injury. These effects attenuate multiple stages of the atherosclerotic process in addition to protecting the heart during resultant ischemic stress, likely underpinning the profound reduction in cardiovascular mortality in hyperbilirubinemic GS. This review outlines our current knowledge of and uses for bilirubin in clinical medicine and summarizes recent progress in revealing the physiological importance of this poorly understood molecule. We believe that this review will be of significant interest to clinicians, medical researchers, and individuals who have GS.»

2019 Amygdala NPY Circuits Promote the Development of Accelerated Obesity under Chronic Stress Conditions

«Neuropeptide Y (NPY) exerts a powerful orexigenic effect in the hypothalamus. However, extra-hypothalamic nuclei also produce NPY, but its influence on energy homeostasis is unclear. Here we uncover a previously unknown feeding stimulatory pathway that is activated under conditions of stress in combination with calorie-dense food; NPY neurons in the central amygdala are responsible for an exacerbated response to a combined stress and high-fat-diet intervention. Central amygdala NPY neuron-specific Npy overexpression mimics the obese phenotype seen in a combined stress and high-fat-diet model, which is prevented by the selective ablation of Npy. Using food intake and energy expenditure as readouts, we demonstrate that selective activation of central amygdala NPY neurons results in increased food intake and decreased energy expenditure. Mechanistically, it is the diminished insulin signaling capacity on central amygdala NPY neurons under combined stress and high-fat-diet conditions that lead to the exaggerated development of obesity.»