Related Metabolic Conditions Research Articles

Dual-Energy Computed Tomography-Guided Assessment of Visceral Adiposity and Its Correlation With Lipid Function Test: A Retrospective Study.

Introduction Obesity, a prevalent global health concern, is associated with various chronic conditions, including cardiovascular diseases and metabolic syndrome. Visceral adiposity, the accumulation of fat around internal organs, has a more significant impact on metabolic health compared to subcutaneous fat. Accurate assessment of visceral fat is critical for predicting metabolic risks. Dual-Energy Computed Tomography (DECT) is emerging as an effective tool for quantifying visceral adiposity, allowing for enhanced tissue differentiation. This study aims to assess visceral adiposity using DECT and explore its correlation with lipid function tests, including cholesterol and triglyceride levels, in a cohort of patients. Materials and methods This retrospective observational study was conducted in the Department of Radiology at Saveetha Medical College and Hospital, Chennai. Data from 100 patientsaged 25 to 75 years with a BMI of 25 kg/m² or higher, were analyzed. DECT scans were performed using a Siemens SOMATOM go.Top 128-slice CT scanner (Siemens, Munich) to quantify visceral fat, particularly mesenteric fat. Lipid function tests were conducted to measure total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. Pearson's correlation coefficient was used to analyze the relationship between visceral fat volume and lipid profile components. Results The study found significant correlations between visceral adiposity and lipid profile components. Total Visceral Fat Area (VFA) volume positively correlated with total cholesterol (r = 0.65, p < 0.01), LDL cholesterol (r = 0.58, p < 0.01), and triglycerides (r = 0.52, p < 0.05). An inverse relationship was observed between VFA volume and HDL cholesterol (r = -0.48, p < 0.05). Regression analysis confirmed that VFA volume is an independent predictor of these lipid levels after adjusting for age, gender, and BMI. The study also reported the prevalence of hepatomegaly in 11 (36.6%) cases and fatty liver in nine (30%) cases in the study population, underscoring the metabolic implications of visceral fat accumulation. Conclusion This study highlights the significant role of visceral adiposity in influencing lipid metabolism and associated cardiovascular risks. DECT proved to be a precise and reliable tool for assessing visceral fat and its metabolic implications. The findings suggest that increased visceral fat is associated with adverse lipid profiles, contributing to a higher risk of metabolic disorders. These results emphasize the need for incorporating advanced imaging techniques like DECT in clinical practice for better risk stratification and personalized treatment strategies in patients with obesity and related metabolic conditions.

Impact of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 Probiotic Supplementation on the Gut Microbiome of Hypercholesterolemia Patients: A Randomized Controlled Trial.

Probiotics have shown potential in managing hypercholesterolemia and related metabolic conditions. This study evaluated the effects of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 on the gut microbiome and metabolic health in patients with hypercholesterolemia, and was registered in the Thai Clinical Trial Registry (TCTR 20220917002). In a randomized, double-blind, placebo-controlled trial, 22 hypercholesterolemic participants received either the probiotic or a placebo daily for 90 days. Fecal samples collected before and after the intervention revealed significant microbiome changes, including a decrease in Subdoligranulum, linked to rheumatoid arthritis, and an increase in Flavonifractor, known for its anti-inflammatory properties. Additionally, the probiotic group exhibited a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels. These findings suggest that L. paracasei TISTR 2593 can modulate the gut microbiome and improve metabolic health, warranting further investigation into its mechanisms and long-term benefits.

The role of FGF19 in metabolic regulation: insights from preclinical models to clinical trials.

Fibroblast growth factor 19 (FGF19) is a hormone synthesized in enterocytes in response to bile acids. This review explores the pivotal role of FGF19 in metabolism, addressing the urgent global health concern of obesity and its associated pathologies, notably type 2 diabetes. The intriguing inverse correlation between FGF19 and body mass or visceral adiposity, as well as its rapid increase following bariatric surgery, emphasizes its potential as a therapeutic target. This article meticulously examines the impact of FGF19 on metabolism by gathering evidence primarily derived from studies conducted in animal models or cell lines, using both FGF19 treatment and genetic modifications. Overall, these studies demonstrate that FGF19 has antidiabetic and antiobesogenic effects. A thorough examination across metabolic tissues, including the liver, adipose tissue, skeletal muscle, and the central nervous system, is conducted, unraveling the intricate interplay of FGF19 across diverse organs. Moreover, we provide a comprehensive overview of clinical trials involving an FGF19 analog called aldafermin, emphasizing promising results in diseases such as nonalcoholic steatohepatitis and diabetes. Therefore, we aim to foster a deeper understanding of FGF19 role and encourage further exploration of its clinical applications, thereby advancing the field and offering innovative approaches to address the escalating global health challenge of obesity and related metabolic conditions.

Korean Red Ginseng Improves Oxidative Stress-Induced Hepatic Insulin Resistance via Enhancing Mitophagy.

This study explored the potential of saponins from Korean Red Ginseng to target the PINK1/Parkin mitophagy pathway, aiming to enhance insulin sensitivity in hepatocytes-a key factor in metabolic disorders like metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes. Results from both in vitro and in vivo experiments showed increased expression of PINK1 and Parkin, activating mitophagy and reducing oxidative stress through reduction in mitochondrial and total reactive oxygen species. Additionally, improvements in insulin signaling were observed, including the upregulation of phosphorylated IRS and AKT, and downregulation of gluconeogenic enzymes, underscoring the saponins' efficacy in boosting insulin sensitivity. The findings highlighted Korean Red Ginseng-derived saponins as potential treatments for insulin resistance and related metabolic conditions.

Association Between Vitamin D and Asymptomatic Hyperuricaemia Among Adults––An Observational Study

Introduction: The relationship between Vitamin D levels and asymptomatic hyperuricaemia is gaining attention due to its potential implications for public health. This study investigates this association, focussing on the interplay between Vitamin D, serum uric acid and parathyroid hormone (PTH) levels in adults. Materials and Methods: This cross-sectional observational study, conducted from April to June 2023, involved 100 adult participants (65 males, 35 females) from the general population. Participants were selected based on specific inclusion and exclusion criteria. Data collection included a comprehensive questionnaire, physical examinations and blood sample analysis. Vitamin D levels were measured using liquid chromatography-tandem mass spectrometry, uric acid levels through an enzymatic colorimetric test, and PTH levels via a chemiluminescent immunoassay. Statistical analysis was performed using SPSS version 25.0, IBM Corp, Chicago, IL, USA. Results: The study found an inverse correlation between Vitamin D and serum uric acid levels. Participants with lower Vitamin D levels had higher serum uric acid and PTH levels. The mean serum Vitamin D level was 32.17 ng/mL, and the mean serum uric acid level was 9.99 mg/dL. The study categorised Vitamin D levels as deficient, insufficient and sufficient, observing significant variations in PTH and uric acid levels across these categories. Conclusion: The study suggests a significant relationship between Vitamin D levels and serum uric acid concentrations in adults, with implications for the management of asymptomatic hyperuricaemia and related metabolic conditions. Despite limitations, such as the cross-sectional design and small sample size, this study highlights the potential significance of Vitamin D levels in the management of asymptomatic hyperuricaemia and related metabolic disorders.

Non-Coding RNAs in Kidney Stones.

Nephrolithiasis is a major public health concern associated with high morbidity and recurrence. Despite decades of research, the pathogenesis of nephrolithiasis remains incompletely understood, and effective prevention is lacking. An increasing body of evidence suggests that non-coding RNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a role in stone formation and stone-related kidney injury. MiRNAs have been studied quite extensively in nephrolithiasis, and a plethora of specific miRNAs have been implicated in the pathogenesis of nephrolithiasis, involving remarkable changes in calcium metabolism, oxalate metabolism, oxidative stress, cell-crystal adhesion, cellular autophagy, apoptosis, and macrophage (Mp) polarization and metabolism. Emerging evidence suggests a potential for miRNAs as novel diagnostic biomarkers of nephrolithiasis. LncRNAs act as competing endogenous RNAs (ceRNAs) to bind miRNAs, thereby modulating mRNA expression to participate in the regulation of physiological mechanisms in kidney stones. Small interfering RNAs (siRNAs) may provide a novel approach to kidney stone prevention and treatment by treating related metabolic conditions that cause kidney stones. Further investigation into these non-coding RNAs will generate novel insights into the mechanisms of renal stone formation and stone-related renal injury and might lead to new strategies for diagnosing and treating this disease.

The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diet: a study protocol for a triple-blind, randomized, placebo-controlled clinical trial

BackgroundObesity is a multifaceted disease characterized by an abnormal accumulation of adipose tissue. Growing evidence has proposed microbiota-derived metabolites as a potential factor in the pathophysiology of obesity and related metabolic conditions over the last decade. As one of the essential metabolites, butyrate affects several host cellular mechanisms related to appetite sensations and weight control. However, the effects of butyrate on obesity in humans have yet to be studied. Thus, the present study was aimed to evaluate the effects of sodium butyrate (SB) supplementation on the expression levels of peroxisome proliferator activated-receptor (PPAR) gamma coactivator-1α (PGC-1α), PPARα and uncoupling protein 1 (UCP1) genes, serum level of glucagon-like peptide (GLP1), and metabolic parameters, as well as anthropometric indices in obese individuals on a weight loss diet.MethodsThis triple-blind randomized controlled trial (RCT) will include 50 eligible obese subjects aged between 18 and 60 years. Participants will be randomly assigned into two groups: 8 weeks of SB (600 mg/day) + hypo-caloric diet or placebo (600 mg/day) + hypo-caloric diet. At weeks 0 and 8, distinct objectives will be pursued: (1) PGC-1α, PPARα, and UCP1 genes expression will be evaluated by real-time polymerase chain reaction; (2) biochemical parameters will be assayed using enzymatic methods; and (3) insulin and GLP1 serum level will be assessed by enzyme-linked immunosorbent assay kit.DiscussionNew evidence from this trial may help fill the knowledge gap in this realm and facilitate multi-center clinical trials with a substantially larger sample size.Trial registrationIranian Registry of Clinical Trials: IRCT20190303042905N2. Registered on 31 January 2021.

Prevalence of obesity and abdominal obesity and their association with metabolic-related conditions in Vietnamese adults: an analysis of Vietnam STEPS survey 2009 and 2015

The abdominal obesity trends and prevalence are important contributing factors to significant rise of many noncommunicable diseases in Vietnam but have not been well-documented in the literature. This study aimed to describe the prevalence and trends of obesity and abdominal obesity in Vietnam from 2009 to 2015 and evaluate how different definitions of obesity and abdominal obesity are associated with metabolic-related conditions. We conducted a secondary analysis based on the Vietnam STEPS (STEPwise approach to Surveillance) cross-sectional Survey 2009 and 2015. Obesity and abdominal obesity were defined using the body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) cut-offs from the World Health Organization (WHO) and International Diabetes Federation (IDF). Depending on the specific cut-offs, from 2009 to 2015, obesity prevalence increased from 0.8%-10% to 1.7%-16.4% in women and from 0.8%-10.3% to 1.7%-15% in men; abdominal obesity prevalence increased from 3%-31.3% to 8%-41.7% in women and from 0.3%-19.3% to 0.4%-25% in men. Abdominal obesity using WC-IDF and WHR-WHO definitions had noticeably higher sensitivity and lower specificity for metabolic-related conditions compared to the other four criteria. All anthropometric measurements were statistically correlated with biomarkers/blood pressure in 2009 and 2015 except for fasting glucose. Only WC-IDF and WHR-WHO definitions showed consistent association with all reported metabolic-related conditions regardless of sex and survey years. The prevalence of obesity and abdominal obesity in Vietnam is increasing rapidly, especially abdominal obesity in women regardless of the criteria used. More studies are needed to investigate how using different diagnostic criteria for obesity and abdominal obesity could better identify metabolic-related conditions. Authors received no funding for this study.

Metabolomic Methods to Predict Cancer-Associated Skeletal Muscle Wasting from Profiles of Urinary Metabolites

It is known that cachexia is a cancer-associated muscle wasting and reduction in the function status due to treatment especially chemotherapy and in life expectancy, to assess cachexia muscle loss there are many methods as Computed Tomography (CT) scan which has many disadvantages as high cost, invasive, time consuming and cannot detect early stages of muscle wasting [1]. This novel approach uses single-time point urinary metabolite profiles for determining whether the patient is subjected to muscle wasting by analysis of 93 random urine samples from patients with cancer using 2 successive CT images by assessing of lumbar skeletal muscle area by cubic centimeter to estimate the rate of muscle change per time for every patient. The average muscle change over time was -4.71% in 100 days in the muscle-losing group and 3.91% in 100 days in the control group. Bivariate statistics identified metabolites to muscle wasting including constituents and metabolites of muscle as creatine and creatinine, amino acids as serine, threonine, glutamic acid, isoleucine and valine. These results suggest that urine analysis of a single random urine sample is cheap, fast, and non-invasive tool to screen muscle loss and it is useful to clarify prediction of related metabolic conditions possible with methodology presented. The metabolomics methods used in this article are Univariate analysis T-test, correlation analysis, principal component analysis and heatmap clustering.

The Effects of Momordica charantia on Type 2 Diabetes Mellitus and Alzheimer’s Disease

T2DM is a complex metabolic disorder characterized by hyperglycemia and glucose intolerance. It is recognized as one of the most common metabolic disorders and its prevalence continues to raise major concerns in healthcare globally. Alzheimer's disease (AD) is a gradual neurodegenerative brain disorder characterized by the chronic loss of cognitive and behavioral function. Recent research suggests a link between the two diseases. Considering the shared characteristics of both diseases, common therapeutic and preventive agents are effective. Certain bioactive compounds such as polyphenols, vitamins, and minerals found in vegetables and fruits can have antioxidant and anti-inflammatory effects that allow for preventative or potential treatment options for T2DM and AD. Recently, it has been estimated that up to one-third of patients with diabetes use some form of complementary and alternative medicine. Increasing evidence from cell or animal models suggests that bioactive compounds may have a direct effect on reducing hyperglycemia, amplifying insulin secretion, and blocking the formation of amyloid plaques. One plant that has received substantial recognition for its numerous bioactive properties is Momordica charantia (M. charantia), otherwise known as bitter melon, bitter gourd, karela, and balsam pear. M. charantia is utilized for its glucose-lowering effects and is often used as a treatment for diabetes and related metabolic conditions amongst the indigenous populations of Asia, South America, India, and East Africa. Several pre-clinical studies have documented the beneficial effects of M. charantia through various postulated mechanisms. Throughout this review, the underlying molecular mechanisms of the bioactive components of M. charantia will be highlighted. More studies will be necessary to establish the clinical efficacy of the bioactive compounds within M. charantia to effectively determine its pertinence in the treatment of metabolic disorders and neurodegenerative diseases, such as T2DM and AD.

The Potential of Lamiaceae Herbs for Mitigation of Overweight, Obesity, and Fatty Liver: Studies and Perspectives.

Numerous plants, plant extracts, and plant-derived compounds are being explored for their beneficial effects against overweight and liver diseases. Obesity is associated with the increased prevalence of non-alcoholic fatty liver disease (NAFLD), becoming the most common liver disease in Western countries. Obesity and NAFLD are closely associated with many other metabolic alternations such as insulin resistance, diabetes mellitus, and cardiovascular diseases. Many herbs of the Lamiaceae family are widely employed as food and spices in the Mediterranean area, but also in folk medicine, and their use for the management of metabolic disorders is well documented. Hereby, we summarized the scientific results of the medicinal and nutraceutical potential of plants from the Lamiaceae family for prevention and mitigation of overweight and fatty liver. The evidence indicates that Lamiaceae plants may be a cost-effective source of nutraceuticals and/or phytochemicals to be used in the management of metabolic-related conditions such as obesity and NAFLD. PubMed, Google Scholar, Scopus, and SciFinder were accessed to collect data on traditional medicinal plants, compounds derived from plants, their reported anti-obesity mechanisms, and therapeutic targets.

3,5-T2-an Endogenous Thyroid Hormone Metabolite as Promising Lead Substance in Anti-Steatotic Drug Development?

Thyroid hormones, their metabolites, and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid beta-oxidation, cholesterol metabolism, and metabolic pathways of glucose homeostasis. Many of these effects are mediated by T3 receptor β1-dependent modulation of transcription. However, rapid non-canonical mitochondrial effects have also been reported, especially for the metabolite 3,5-diiodothyronine (3,5-T2), which does not elicit the full spectrum of “thyromimetic” actions inherent to T3. Most preclinical studies in rodent models of obesity and first human clinical trials are promising with respect to the antisteatotic hepatic effects, but potent agents exhibit unwanted thyromimetic effects on the heart and/or suppress feedback regulation of the hypothalamus-pituitary-thyroid-periphery axis and the fine-tuned thyroid hormone system. This narrative review focuses on 3,5-T2 effects on hepatic lipid and glucose metabolism and (non-)canonical mechanisms of action including its mitochondrial targets. Various high fat diet animal models with distinct thyroid hormone status indicate species- and dose-dependent efficiency of 3,5-T2 and its synthetic analogue TRC150094. No convincing evidence has been presented for their clinical use in the prevention or treatment of obesity and related metabolic conditions.

Silk Hydrogel-Mediated Delivery of Bone Morphogenetic Protein 7 Directly to Subcutaneous White Adipose Tissue Increases Browning and Energy Expenditure.

Objective: Increasing the mass and/or activity of brown adipose tissue (BAT) is one promising avenue for treating obesity and related metabolic conditions, given that BAT has a high potential for energy expenditure and is capable of improving glucose and lipid homeostasis. BAT occurs either in discrete “classical” depots, or interspersed in white adipose tissue (WAT), termed “inducible/recruitable” BAT, or ‘beige/brite’ adipocytes. We and others have demonstrated that bone morphogenetic protein 7 (BMP7) induces brown adipogenesis in committed and uncommitted progenitor cells, resulting in increased energy expenditure and reduced weight gain in mice. BMP7 is therefore a reliable growth factor to induce browning of WAT. Methods: In this study, we sought to deliver BMP7 specifically to subcutaneous (sc)WAT in order to induce tissue-resident progenitor cells to differentiate into energy-expending recruitable brown adipocytes, without off-target effects like bone formation, which can occur when BMPs are in the presence of bone progenitor cells (outside of WAT). BMP7 delivery directly to WAT may also promote tissue innervation, or directly activate mitochondrial activity in brown adipocytes, as we have demonstrated previously. We utilized silk protein in the form of an injectable hydrogel carrying BMP7. Silk scaffolds are useful for in vivo delivery of substances due to favorable material properties, including controlled release of therapeutic proteins in an active form, biocompatibility with minimal immunogenic response, and prior FDA approval for some medical materials. For this study, the silk was engineered to meet desirable release kinetics for BMP7 in order to mimic our prior in vitro brown adipocyte differentiation studies. Fluorescently-labeled silk hydrogel loaded with BMP7 was directly injected into WAT through the skin and monitored by non-invasive in vivo whole body imaging, including in UCP1-luciferase reporter mice, thereby enabling an approach that is translatable to humans. Results: Injection of the BMP7-loaded silk hydrogels into the subcutaneous WAT of mice resulted in “browning”, including the development of multilocular, uncoupling protein 1 (UCP1)-positive brown adipocytes, and an increase in whole-body energy expenditure and skin temperature. In diet-induced obese mice, BMP7-loaded silk delivery to subcutaneous WAT resulted in less weight gain, reduced circulating glucose and lower respiratory exchange ratio (RER). Conclusions: In summary, BMP7 delivery via silk scaffolds directly into scWAT is a novel translational approach to increase browning and energy expenditure, and represents a potential therapeutic avenue for delivering substances directly to adipose depots in pursuit of metabolic treatments.

Liver stiffness and steatosis in preeclampsia as shown by transient elastography–a prospective cohort study

Preeclampsia is a multisystem disorder and the leading cause of severe morbidity and death in pregnancy. Liver involvement in preeclampsia ranges from elevated liver enzyme levels to hepatic infarction or rupture. Endothelial dysfunction leads to changes in blood flow and congestion and may be involved in the pathophysiology of preeclampsia. Changes in splanchnic blood flow and portal congestion can lead to altered liver stiffness. Transient elastography is a noninvasive, ultrasound-based technique that measures organ stiffness and steatosis and is therefore widely used in clinical hepatology. Previous studies reported elevated liver stiffness and liver steatosis, as measured by transient elastography, in women with preeclampsia. This study followed changes in liver stiffness and steatosis, as measured by transient elastography, from the antepartum period to 1-week postpartum among women with preeclampsia compared with healthy controls and evaluated the association between preeclampsia severity and transient elastography results. This prospective cohort study was conducted from 2017 through 2021. The study group comprised women with preeclampsia, and the control group comprised healthy pregnant women hospitalized for other reasons. All the participants underwent transient elastography either on diagnosis of preeclampsia (study group) or on hospital admission (control group) and again in the postpartum period. Liver stiffness measurements are expressed in kilopascals (kPa) in the range of 2.5 to 75 kPa, and liver steatosis isexpressed by controlled attenuation parameter in the range of 100 to 400 dB/m. The study group comprised 36 women and the control group 37. Liver stiffness scores were significantly elevated in the study when compared with the control group, both in the antepartum period (P<.001) and the postpartum period (P=.025). Liver stiffness scores decreased significantly after delivery in the study and control groups (P<.001 and P=.002, respectively). Liver steatosis scores were higher in the study group than in the control group both in the antepartum and postpartum periods (P<.001 and P<.02, respectively). In the multivariable analysis, the diagnosis of preeclampsia correlated with higher antepartum liver stiffness scores (P=.005). For the study group, postpartum liver stiffness and liver steatosis scores were increased among those with vs those without severe features of preeclampsia (P=.03 and P=.04, respectively) CONCLUSION: Reductions in liver stiffness and steatosis from the antepartum to the postpartum period were documented in both the preeclampsia and control groups. However, both these measures were higher in the preeclampsia group and correlated with preeclampsia severity. Larger studies may be able to determine whether transient elastography can predict the severity of preeclampsia or other related metabolic conditions that correlate with chronic hypertension.

Role of Sumac (Rhus coriaria L.) in the management of metabolic syndrome and related disorders: Focus on NAFLD-atherosclerosis interplay

Sumac (Rhus coriaria L.) is a commonly used spice in the Mediterranean region and considered as healthy food ingredients. The beneficial value of sumac is well documented in folk medicine. Accumulating data explored the phytochemical, nutritional and therapeutic proprieties suggesting sumac as a potential functional food. Here, we discuss the general and scientific aspects of sumac. Sumac is rich in different polyphenolic compounds such as flavonoids, tannins, and phenolic acids. The potential therapeutic effects of sumac have been studied in various cellular and animal models, as well as in human. These reports suggest that Sumac has potential effect against oxidative stress, inflammation, obesity, hyperglycemia, hypercholesterolemia, and hyperlipidemia, which represent key pathogenic mechanisms contributing to cardio-metabolic, liver, and cancer diseases. Clinical studies using sumac or its major compounds, suggest that this herbal product may represent a useful therapeutic tool in the management of metabolic-related conditions such as liver-atherosclerosis complications.

Adult but not childhood onset asthma is associated with the metabolic syndrome, independent from body mass index

IntroductionAdult-onset asthma (AOA) is usually more severe compared to childhood onset asthma (CoA). Given the increasing evidence that AoA is associated with obesity, we investigated the relationship of other related metabolic comorbid conditions with AoA compared to CoA. Study design and methodsThis cross-sectional study compared the metabolic syndrome and lipid derived inflammatory markers in patients with AoA, CoA and age- and sex-matched control subjects without asthma. Participants were asthma patients visiting the outpatient clinic of two teaching hospitals in Rotterdam, The Netherlands. All participants underwent lung function tests, blood tests and physical activity tracking. AoA was defined as asthma age of onset after the age of 18 years. Metabolic syndrome was defined according to the international joint interim statement criteria. ResultsEighty-one participants were included (27 AoA, 25 CoA, 29 controls). AoA was associated with the metabolic syndrome (Odds Ratio = 3.64 95% CI (1.16–11.42) p = 0.03, Nagelkerke R2 = 0.26), adjusted for age, sex, body mass index and smoking habits. AoA patients had higher median serum IL-6 and leptin-adiponectin (LA) ratio compared to controls (IL-6 (pg/mL): 3.10 [1.11–4.30] vs. 1.13 [0.72–1.58], p = 0.002 and LA ratio (pg/mL): 6.21 [2.45–14.11] vs. 2.24 [0.67–4.71], p = 0.0390). This was not observed in CoA and controls. ConclusionAoA was associated with the metabolic syndrome and its related pro-inflammatory endocrine and cytokine status. This may suggest adipose tissue derived inflammatory markers play a role in the pathophysiology of AoA.

Modeling and simulation in medical sciences: an overview of specific applications based on research experience in EMRI (Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences).

The concomitant use of various types of models (in silico, in vitro, and in vivo) has been exemplified here within the context of biomedical researches performed in the Endocrinology and Metabolism Research Institute (EMRI) of Tehran University of Medical Sciences. Two main research aeras have been discussed: the search for new small molecules as therapeutics for diabetes and related metabolic conditions, and diseases related to protein aggregation. Due to their multidisciplinary nature, the majority of these studies have needed the collaboration of different specialties. In both cases, a brief overview of the subject is provided through literature examples, and sequential use of these methods is described.

Associations between Helicobacter pylori with nonalcoholic fatty liver disease and other metabolic conditions in Guatemala.

Previous studies have suggested an association between Helicobacter pylori (Hpylori) and nonalcoholic fatty liver disease (NAFLD). The aim of the current study was to examine the association in Guatemala, a region with elevated prevalences of both Hpylori and NAFLD. Associations between Hpylori and other metabolic conditions were also examined, as were associations between Hhepaticus and Hbilis and the metabolic conditions. The analysis included 424 participants from a cross-sectional study in Guatemala. Hpylori seropositivity was defined as positivity for≥4 antigens. Seropositivities for Hbilis and Hhepaticus were defined as positivity for≥2 antigens. NAFLD was estimated using the Fatty Liver Index and the Hepatic Steatosis Index. Other conditions examined were obesity, central obesity, hypercholesterolemia, low HDL, diabetes and metabolic syndrome (MetSyn). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated. No overall associations between Hpylori,Hhepaticus, or Hbilis and NAFLD or related metabolic conditions were found. Seropositivity for Hpylori antigens CagA and VacA and Hhepaticus antigen HH0713 was each significantly associated with NAFLD, however. In addition, associations were observed between the Hpylori antigens HyuA, HP1564, and UreA and specified metabolic conditions. While no overall associations between Hpylori or Helicobacter species with NAFLD or related conditions were observed, some selected Helicobacter spp. antigens were associated with NAFLD. Further research is warranted to examine whether H. species are associated with any metabolic condition.

The Link Between Social Determinants of Health, Sleep, and Cardiovascular Disease

Chronic sleep insufficiency or long-sleep duration appears to contribute to the development of cardiovascular disease (CVD) and other related metabolic conditions, including obesity and type 2 diabetes mellitus. Emerging evidence suggests that effective treatment of a sleep disorder may prevent subsequent cardiovascular events. Therefore, promotion of optimal sleep and the identification and adequate treatment of sleep disorders earlier in life may prevent or reduce the risk of CVD and the subsequent consequences of CVD. Promotion of optimal health behaviors, including sleep health, need to consider how social determinants of health (SDOH) influence and affect the ability of individuals to adequately and effectively incorporate health behavior recommendations into their daily lives. Therefore, the purpose of this perspective article is to (1) discuss how persistent deviation from the recommended amount and quality of sleep contributes to the development of CVD; and (2) discuss how SDOH across the levels of the Social–Ecological Model influence sleep health and potentially CVD.

PAR2 controls cholesterol homeostasis and lipid metabolism in nonalcoholic fatty liver disease

ObjectiveIncreases in hepatic and plasma cholesterol occur in patients with nonalcoholic fatty liver disease (NAFLD), although the reason for this is not well understood. We investigated whether Protease-Activated Receptor 2 (PAR2) plays a role in cholesterol and lipid homeostasis in NAFLD. MethodsHuman liver biopsies (n = 108) were quantified for PAR2 expression from NAFLD cases randomly selected and stratified by liver fibrosis stage, the primary predictor for clinical outcomes, while controlling for age, gender, and BMI between fibrosis groups. Demographic data and laboratory studies on plasma samples were obtained within 6 months of liver biopsy. Wild-type and PAR2-KO (C57BL/6 F2rl1−/−) mice were fed either normal or high fat diet for 16 weeks and plasma and liver assayed for lipids and soluble metabolites. ResultsSeverity of NAFLD and plasma cholesterol levels significantly correlated with hepatocyte PAR2 expression in NAFLD patients. Conversely, PAR2 deficiency in mice resulted in reduced expression of key hepatic genes involved in cholesterol synthesis, a 50% drop in plasma and total liver cholesterol, and induced a reverse cholesterol transport system that culminated in 25% higher fecal bile acid output. PAR2-deficient mice exhibited enhanced fatty acid β-oxidation with a ketogenic shift and an unexpected increase in liver glycogenesis. Mechanistic studies identified Gi-Jnk1/2 as key downstream effectors of protease-activated PAR2 in the regulation of lipid and cholesterol homeostasis in liver. ConclusionsThese data indicate that PAR2 may be a new target for the suppression of plasma cholesterol and hepatic fat accumulation in NAFLD and related metabolic conditions.