Hepatic Transporters Alternations Associated with Non-alcoholic Fatty Liver Disease (NAFLD): A Systematic Review.
European journal of drug metabolism and pharmacokinetics. 2023;(1):1-10
BACKGROUND AND OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disorder and is usually accompanied by obesity, metabolic syndrome, and diabetes mellitus. NAFLD progression can lead to impaired functions of hepatocytes such as alternations in expression and function of hepatic transporters. The present study aimed to summarize and discuss the results of clinical and preclinical human studies that investigate the effect of NAFLD on hepatic transporters. METHODS The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to 1 March 2022. The risk of bias was assessed for cross-sectional studies through the Newcastle-Ottawa Scale score. RESULTS Our review included ten cross-sectional studies consisting of 485 participants. Substantial alternations in hepatic transporters were seen during NAFLD progression to non-alcoholic steatohepatitis (NASH) in comparison with control groups. A significant reduction in expression and function of several hepatic uptake transporters, upregulation of many efflux transporters, downregulation of cholesterol efflux transporters, and mislocalization of canalicular transporter ABCC2 are associated with NAFLD progression. CONCLUSION Since extensive changes in hepatic transporters could alter the pharmacokinetics of the drugs and potentially affect the safety and efficacy of drugs, close monitoring of drug administration is highly suggested in patients with NASH.
Effects of fenugreek supplementation on the components of metabolic syndrome: A systematic review and dose-response meta-analysis of randomized clinical trials.
Pharmacological research. 2023;:106594
Metabolic syndrome (MetS) is a cluster of metabolic disorders with a heavy disease burden. Fenugreek was reported to be effective in some components of MetS. Therefore, a comprehensive review and meta-analysis of randomized controlled trials was conducted to study the effects of fenugreek on MetS indices. From the beginning until August 2022, PubMed, Embase, Scopus, and Web of science were searched. Data were analyzed using the random-effect model, and presented as weighted mean difference (WMD) and associated 95 % confidence interval (CI). This meta-analysis comprised from a total of 29 eligible RCTs with 31 arms measuring fasting plasma glucose (FPG), Triglyceride (TG), high-density lipoprotein (HDL), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The results indicated significant improving effects of fenugreek on FPG (WMD: -16.75 mg/dL; 95 % CI: -23.36, -10.15; P < 0.001), TG (-20.12 mg/dL; 95 % CI: -34.238, -5.994; P < 0.001), HDL (WMD: 3.55 mg/dL; 95 % CI: 1.98, 5.12; P < 0.001), WC (WMD: -2.51; 95 % CI: -3.78, -1.24; P < 0.001) and SBP (WMD: -3.45 mmHg; 95 % CI: -6.38, -0.52; P = 0.021); However the effect on DBP (WMD: 3.17; 95 % CI: -5.40, 11.73; P = 0.469) and BMI (WMD: -0.40 kg/m2; 95 % CI: -1.114, 0.324; P = 0.281) was not significant. Administration of fenugreek can meaningfully reduce FPG, TG, WC, and SBP and increase HDL. The overall results support possible protective and therapeutic effects of fenugreek on MetS parameters.
Health benefits of proanthocyanidins linking with gastrointestinal modulation: An updated review.
Food chemistry. 2023;(Pt A):134596
Proanthocyanidins (PACs) are the bioactive components naturally present in daily diet, especially in fruits and vegetables. Multiple pieces of evidence suggested that ingestion of PACs or diets full of PACs might contribute to physiological benefits, such as metabolic syndrome regulation, immune modulation, cancer prevention, and neuroprotection. Many studies stated that dysbiosis is closely linked with the abovementioned health conditions, and the extremely poor bioavailability of PACs, directly associated with the structural diversity, leads to extensively metabolized through gut microbiota (GM). GM transforms PACs into bioactive metabolites. Conversely, PACs also modulate the gut microbiome and the composition of GM. Thus, the complex bidirectional interactions between PACs and gut microbiota might help to understand the ambiguity between bioavailability and pleiotropic bioactivity. In this review, we summarize recent in vivo and in vitro studies from the aspect of intestinal function of PACs and its associated disease, as well as the underlying mechanisms.
Tophaceous gout in a young man with Gitelman syndrome: a case report with an overview.
Clinical rheumatology. 2023;(1):285-291
Gitelman syndrome represents the clinical manifestations of inactivation of the Slc12a3 genes encoding the thiazide-sensitive sodium chloride cotransporter and the Trpm6-Mg genes encoding the magnesium transporters in the distal convoluted tubule. In fact, the biochemical findings resemble those with thiazide diuretics such as hypokalemia, hypomagnesaemia, hypocalciuria, metabolic alkalosis, and low normal blood pressure. He is usually associated with calcium pyrophosphate deposition. Serum uricemia level is rarely affected in Gitelman syndrome. We aimed to report a rare association of chronic gout with Gitelman syndrome, hence the interest of our case. We describe a 29-year-old male patient with a history of Gitelman syndrome associated with articular gout including pelvic localization. We provided pictorial evidence of extensive and diffuse monosodium urate deposition in articular and periarticular structures to confirm the gout origin. A literature review illustrates 4 reported cases of Gitelman syndrome associated with gout. The gender distribution was equal with a mean age of 40 years.
Alcohol consumption and metabolic syndrome: Clinical and epidemiological impact on liver disease.
Journal of hepatology. 2023;(1):191-206
Alcohol use and metabolic syndrome are highly prevalent in the population and frequently co-exist. Both are implicated in a large range of health problems, including chronic liver disease, hepatocellular carcinoma, and liver-related outcomes (i.e. decompensation or liver transplantation). Studies have yielded mixed results regarding the effects of mild-moderate alcohol consumption on the risk of metabolic syndrome and fatty liver disease, possibly due to methodological differences. The few available prospective studies have indicated that mild-moderate alcohol use is associated with an increase in liver-related outcomes. This conclusion was substantiated by systems biology analyses suggesting that alcohol and metabolic syndrome may play a similar role in fatty liver disease, potentiating an already existing dysregulation of common vital homeostatic pathways. Alcohol and metabolic factors are independently and jointly associated with liver-related outcomes. Indeed, metabolic syndrome increases the risk of liver-related outcomes, regardless of alcohol intake. Moreover, the components of metabolic syndrome appear to have additive effects when it comes to the risk of liver-related outcomes. A number of population studies have implied that measures of central/abdominal obesity, such as the waist-to-hip ratio, can predict liver-related outcomes more accurately than BMI, including in individuals who consume harmful quantities of alcohol. Many studies even point to synergistic interactions between harmful alcohol use and many metabolic components. This accumulating evidence showing independent, combined, and modifying effects of alcohol and metabolic factors on the onset and progression of chronic liver disease highlights the multifactorial background of liver disease in the population. The available evidence suggests that more holistic approaches could be useful for risk prediction, diagnostics and treatment planning.
Polyphenols: a route from bioavailability to bioactivity addressing potential health benefits to tackle human chronic diseases.
Archives of toxicology. 2023;(1):3-38
Chronic pathologies or non-communicable diseases (NCDs) include cardiovascular diseases, metabolic syndrome, neurological diseases, respiratory disorders and cancer. They are the leading global cause of human mortality and morbidity. Given their chronic nature, NCDs represent a growing social and economic burden, hence urging the need for ameliorating the existing preventive strategies, and for finding novel tackling therapies. NCDs are highly correlated with unhealthy lifestyle habits (such as high-fat and high-glucose diet, or sedentary life). In general, lifestyle approaches that might improve these habits, including dietary consumption of fresh vegetables, fruits and fibers, may contrast NCD symptoms and prolong life expectancy of affected people. Polyphenols (PPLs) are plant-derived molecules with demonstrated biological activities in humans, which include: radical scavenging and anti-oxidant activities, capability to modulate inflammation, as well as human enzymes, and even to bind nuclear receptors. For these reasons, PPLs are currently tested, both preclinically and clinically, as dietary adjuvants for the prevention and treatment of NCDs. In this review, we describe the human metabolism and bioactivity of PPLs. Also, we report what is currently known about PPLs interaction with gastro-intestinal enzymes and gut microbiota, which allows their biotransformation in many different metabolites with several biological functions. The systemic bioactivity of PPLs and the newly available PPL-delivery nanosystems are also described in detail. Finally, the up-to-date clinical studies assessing both safety and efficacy of dietary PPLs in individuals with different NCDs are hereby reported. Overall, the clinical results support the notion that PPLs from fruits, vegetables, but also from leaves or seeds extracts, are safe and show significant positive results in ameliorating symptoms and improving the whole quality of life of people with NCDs.
Secular trend for increasing birthweight in offspring of pregnant women with type 1 diabetes: is improved placentation the reason?
Despite enormous progress in managing blood glucose levels, pregnancy in women with type 1 diabetes still carries risks for the growing fetus. While, previously, fetal undergrowth was not uncommon in these women, with improved maternal glycaemic control we now see an increased prevalence of fetal overgrowth. Besides short-term implications, offspring of women with type 1 diabetes are more likely to become obese and to develop diabetes and features of the metabolic syndrome. Here, we argue that the increase in birthweight is paradoxically related to improved glycaemic control in the pre- and periconceptional periods. Good glycaemic control reduces the prevalence of microangiopathy and improves placentation in early pregnancy, which may lead to unimpeded fetal nutrition. Even mild maternal hyperglycaemia may then later result in fetal overnutrition. This notion is supported by circumstantial evidence that lower HbA1c levels as well as increases in markers of placental size and function in early pregnancy are associated with large-for-gestational age neonates. We also emphasise that neonates with normal birthweight can have excessive fat deposition. This may occur when poor placentation leads to initial fetal undergrowth, followed by fetal overnutrition due to maternal hyperglycaemia. Thus, the complex interaction of glucose levels during different periods of pregnancy ultimately determines the risk of adiposity, which can occur in fetuses with both normal and elevated birthweight. Prevention of fetal adiposity calls for revised goal setting to enable pregnant women to maintain blood glucose levels that are closer to normal. This could be supported by continuous glucose monitoring throughout pregnancy and appropriate maternal gestational weight gain. Future research should consider the measurement of adiposity in neonates.
Effect of positive pressure ventilation and bariatric surgery on extracellular vesicle microRNAs in patients with severe obesity and obstructive sleep apnea.
International journal of obesity (2005). 2023;(1):24-32
INTRODUCTION Obstructive sleep apnea (OSA) and severe obesity share a common pathophysiological phenomenon, systemic and tissue hypoxia. Hypoxaemia modifies microRNA expression, particularly, extracellular vesicles microRNAs which are involved in the progression of cardiovascular diseases, metabolic syndrome and cancer. We aim to evaluate extracellular vesicle miRNAs among patients with severe obesity with and without OSA and the effect of OSA and severe obesity treatment: continuous positive airway pressure (CPAP) and bariatric surgery. METHODS Patients were selected from the Epigenetics Modification in Morbid Obesity and Obstructive Sleep Apnea (EPIMOOSA) study (NCT03995836), a prospective observational study of patients undergoing bariatric surgery. Patients were divided into OSA (Apnea-hyponea index (AHI) > 10) and non-OSA (AHI < 10). Patients with OSA were treated with CPAP for 6 months. Then, all patients had bariatric surgery and re-evaluated 12 months later. At each visit, blood samples were obtained for biobanking. Subsequently, extracellular vesicles were extracted, and then, miRNA expression was analysed. RESULTS 15 patients with OSA and 9 without OSA completed the protocol. At baseline, patients with OSA showed higher miR16, miR126 and miR320 (p < 0.05) and lower miR223 expression (p < 0.05) than those without OSA. In patients with severe obesity and OSA, after 6 months with CPAP, we observed a significant decrease in miR21 (p < 0.01), miR126 (p < 0.001) and miR320 (p < 0.001), with no changes in any miRNA in patients without OSA. No changes were detected in any miRNA after 6 months of bariatric surgery in patients with or without OSA. CONCLUSION Co-existance of OSA and severe obesity alters the profile of extracellular vesicle miRNAs. Bariatric surgery and weight loss did not reverse this effect meanwhile the treatment with CPAP in patients with severe obesity and OSA showed a recovery outcome in those extracellular vesicle miRNAs. Those facts remark the need for OSA screening in patients with severe obesity. CLINICAL TRIAL REGISTRATION The study has also been registered at ClinicalTrials.gov identifier: NCT03995836.
Examining the relationship between obstructive sleep apnoea and eating behaviours and attitudes: A systematic review.
BACKGROUND Between 60 and 90% of adults with OSA are reported as overweight. The co-existence of obesity and OSA can greatly increase an individual's risk of type 2 diabetes, metabolic syndrome and cardiovascular disease. To better understand this relationship between OSA and weight, this review aimed to investigate if there is evidence of certain eating behaviours or eating attitudes that might be found in adults living with OSA. METHODS We searched four databases (MEDLINE, Embase, PsycInfo and Web of Science) on January 17th, 2022, to identify studies assessing the association between eating patterns and OSA in adults. Twenty-one studies met the inclusion criteria. A narrative synthesis was conducted on the included studies, following the vote-counting method. RESULTS There is preliminary evidence that the time of day when calories are consumed is associated with lower OSA severity. No other clear patterns of eating behaviours or attitudes were identified however this may be due to disparity within research studies and their reported results. CONCLUSION Further research is needed to examine the relationship between eating times and OSA severity. We recommend standardising the approach to examining the eating patterns of those living with OSA and the relationship that this might have on OSA symptoms as well as looking at attitudes towards food in this population. This may prove helpful in providing a better understanding of the relationship between OSA and persons with overweight and help in future intervention development.
Bone marrow oxalosis with pancytopenia in a patient with short bowel syndrome: Report of a case and review of the literature.
JPEN. Journal of parenteral and enteral nutrition. 2023;(1):165-170
Systemic oxalosis is a condition in which calcium oxalate crystals deposit into various bodily tissues. Although this may occur as the result of a rare primary syndrome in which an error of glyoxylate metabolism causes an overproduction of oxalate, it is more often seen as a secondary process characterized by increased enteric oxalate absorption. Here, we describe a patient with short bowel syndrome on long-term parenteral nutrition support who developed a unique manifestation of systemic oxalosis, leading to deposition of oxalate crystals within the bone marrow contributing to pancytopenia. In this report, in addition to reviewing the literature on this presumably rare manifestation of oxalosis, we also discuss its pathogenesis in the setting of short bowel syndrome and its management, including prevention.