Obesity Syndrome Research Articles

Sex-based differences in metabolic protection by the ANP genetic variant rs5068 in the general population.

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are produced in the heart and secreted into the circulation. As hormones, both peptides activate the guanylyl cyclase receptor A (GC-A), playing a role in blood pressure (BP) regulation. A significant role for ANP and BNP includes favorable actions in metabolic homeostasis. Sex-based high prevalence of risk factors for cardiovascular disease in males compared with females is well established, but sex-based differences on cardiometabolic protection have not been investigated in relation to ANP (NPPA) and BNP (NPPB) gene variants. We included 1,146 subjects in the general population from Olmsted County, Minnesota. Subjects were genotyped for the ANP gene variant rs5068 and BNP gene variant rs198389. Cardiometabolic parameters and medical records were reviewed. In the presence of the minor allele of rs5068, diastolic BP, creatinine, body mass index (BMI), waist measurement, insulin, and prevalence of obesity and metabolic syndrome were lower, whereas HDL was higher in males with only trends observed in females. We observed no associations of the minor allele with echocardiographic parameters in either males or females. Regarding rs198389 genotype, the minor allele was not associated with any BP, metabolic, renal, or echocardiographic parameters in either sex. In the general community, the minor allele of the ANP gene variant rs5068 is associated with a favorable metabolic phenotype in males. No associations were observed with the BNP gene variant rs198389. These studies support a protective role of the ANP pathway on metabolic function and underscore the importance of sex in relationship to natriuretic peptide responses.NEW & NOTEWORTHY Males are characterized by lower ANP and BNP with greater prevalence of cardiometabolic disease. The ANP genetic variant rs5068 was associated with less metabolic dysfunction in males, whereas no metabolic profile was related to the BNP genetic variant rs198389 in the general population. ANP may play a more biological role in metabolic homeostasis compared with BNP in the general population with greater physiological metabolic actions in males compared with females.

Abstract P379: Acute Mineralocorticoid Receptor Antagonism Does Not Alter Insulin Sensitivity Or Secretion In Metabolic Syndrome

We previously demonstrated that maximal dietary sodium restriction impairs insulin secretion in humans, and that aldosterone impairs insulin secretion ex vivo in isolated islets. Aldosterone is inappropriately elevated in obesity and metabolic syndrome, but it is unknown if mineralocorticoid receptor antagonism with eplerenone improves insulin secretion in metabolic syndrome (MS) during moderate sodium restriction. We hypothesized that eplerenone would improve insulin secretion and insulin sensitivity in participants with the metabolic syndrome. We conducted a randomized, double-blind cross-over study in 16 volunteers with MS and elevated blood pressure in whom we provided either Eplerenone 50 mg or Amlodipine 5 mg and a standardized 50mmol Na/day diet for 7 days. Insulin sensitivity was assessed with hyperinsulinemic clamp and insulin secretion was assessed with hyperglycemic clamp at 5 and 7 days of diet, respectively. EPL increased plasma aldosterone compared to AML treatment (19.8±9.3 vs 12.2±3.9 ng/dL, in EPL and AML, respectively; mean±SD, for all descriptions; P <0.001) but did alter systolic blood pressure (127.5±15.6 vs 124.5±14.5 mmHg; P =0.51). EPL did not alter insulin sensitivity assessed by hyperinsulinemic clamp (19.3±7.8 vs 18.7±7.3 μg/kg/min per uU/mL Insulin; P =0.82).Fasting glucose (101.8±9.0 vs 100.5±6.8 mg/dL, P=0.76) and insulin (28.1±18.0 vs 23.9±12.7 μU/mL; P =0.7) were similar during EPL treatment. EPL did not alter acute glucose-stimulated insulin secretion (68.2±45.5 vs 58.7±43.7 μU/ml; P =0.7) or L-arginine stimulated insulin secretion (578±238 vs 579±228 μU/ml; P =0.8) assessed by hyperglycemic clamp. Disposition index was similarly unchanged (1.2±0.8 vs 1.1±0.9; P =0.8). We conclude that mineralocorticoid receptor antagonism with eplerenone during 7 days of moderate sodium restriction does not alter insulin sensitivity or insulin secretion in Metabolic Syndrome.

Linking serum vitamin D levels with gut microbiota after 1-year lifestyle intervention with Mediterranean diet in patients with obesity and metabolic syndrome: a nested cross-sectional and prospective study

ABSTRACT Vitamin D, microbiota, and the Mediterranean diet (MedDiet) have been the focus of recent research due to their potential role in maintaining overall health. We hypothesize that MedDiet may alter the gut microbiota profile through changes in vitamin D levels. We aimed to investigate changes in gut microbiota and serum vitamin D levels after a MedDiet within a lifestyle intervention. The study included 91 patients with obesity and metabolic syndrome, who were categorized based on their serum vitamin D levels as having either optimal or low 25-hydroxyvitamin D [25(OH)D levels]. The profile of the gut microbiota was analyzed by the 16S rRNA sequencing, inferring its functionality through PICRUsT. Participants underwent a hypocaloric MedDiet and change in their lifestyle for 1 year, and the profile and functionality of their gut microbiota were evaluated by analyzing inter-individual differences in time. At baseline, gut microbiota profiles qualitatively differed between participants with Optimal or Low 25(OH)D levels [Unweighted (p = 0.016)]. Moreover, participants with Optimal 25(OH)D levels showed a higher gut microbiota diversity than those with Low 25(OH)D levels (p < 0.05). The differential analysis of abundance between the Low and Optimal 25(OH)D groups revealed differences in the levels of Bacteroides, Prevotella, and two Clostridiales features. After 1-year dietary intervention, both groups increased their 25(OH)D levels. Furthermore, both groups did not show significant differences in gut microbiota diversity, although the Low 25(OH)D group showed greater improvement in gut microbiota diversity by comparing at baseline and after dietary intervention (p < 0.05). Changes in specific bacterial taxa were observed within each group but did not differ significantly between the groups. Metabolic pathway analysis indicated differences in microbial functions between the groups (p < 0.05). These findings suggest that 25(OH)D status is associated with gut microbiota composition, diversity, and functionality, and lifestyle intervention can modulate both gut microbiota and 25(OH)D levels, potentially influencing metabolic pathways.

Correlation between Uric Acid Levels and the Severity of Psoriasis Vulgaris Patients

Introduction: Psoriasis vulgaris (PV) is a recurrent chronic inflammatory skin disease characterized by erythematous, scaly, well-defined plaques with the greatest predilection, generally in the areas of the elbows, knees, scalp, and lower back. The psoriasis area and severity index (PASI) is one of the most widely used evaluation tools to determine the development of psoriasis vulgaris in a patient. Hyperuricemia is the dominant risk factor for PV when compared to other known risk factors, such as obesity or metabolic syndrome. This study aimed to determine whether there is a relationship between serum uric acid levels and the severity of PV based on the PASI score.&#x0D; Methods: Cross-sectional study with one-time sampling conducted from December 2021 to February 2022 in psoriasis vulgaris patients who came to the Dermatology and Venereology clinic at Dr. Moewardi General Hospital, Surakarta, Indonesia. All data were statistically analyzed using SPSS 26. Variables, including age, gender, disease duration, body mass index, and uric acid levels, were subjected to univariate analysis. Bivariate analysis was then followed by a parametric test. The p-value &lt;0.05 was considered significant.&#x0D; Results: There were 36 patients during the study period. The average uric acid level was 6.0135, with an average PASI score of 10.6388. The relationship between uric acid levels and the severity of psoriasis vulgaris was found to be significant, with a value of p = 0.025.&#x0D; Conclusion: There is a significant relationship between uric acid levels and the severity of psoriasis vulgaris, where the higher the uric acid level, the more severe the severity of psoriasis vulgaris.

Patatin-Like Phospholipase Domain Containing 3 (PNPLA3) as a Non-Invasive Marker in Diagnosis of NASH

Abstract Background Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of progressive liver disease characterized by increased hepatic triglyceride content (HTGC) in the absence of excess alcohol consumption. NAFLD includes simple steatosis, non-alcoholic steatohepatitis, fibrosis and ultimately cirrhosis, and is strongly associated with features of the metabolic syndrome (obesity, insulin resistance/type 2 diabetes mellitus and dyslipidemia). Objective To study the role of PNPLA3 as non-invasive biomarker in diagnosis of NASH. Patients and Methods Single Centre randomized case control clinical study This study was conducted for patients attended Bariatric surgery unit at Ain-Shams University Hospital. Literature review designed and data collection started in October 2019 up to March 2021. This study performed on 50 Egyptian patients, proven NAFLD by histology, patients were biopsied during a bariatric Surgery at Ain-Shams University Hospital after written consent were obtained, and 25 healthy control Subjects were selected randomly after meted the criteria. Results The G risk allele shows higher level of ALT and statistically significant (p &amp;lt; 0.028*) but not significant with AST (p &amp;lt; 0.243), significant with triglycerides (p &amp;lt; 0.013*), with total cholesterol (p &amp;lt; 0.010*) and BMI (p &amp;lt; 0.016*) independent of the others parameter compared to wild type C allele. To greater number of G risk allele more higher scoring of NAS score (p &amp;lt; 0.002*) and increasing likelihood of advance fibrosis stage (p &amp;lt; 0.046*). By dominant analysis 54.77% of the steatohepatitis patients carrying the risk allele G while steatosis group only 22.42% carrying the risk allele the risk G allele had 4.19 fold more risk of having sheatohepatitis (NASH) than the wild type C allele among the studied NAFLD patients group (odds ratio 4.19, CI 95% 1.762-9.962, p &amp;lt; 0.001*). Homozygous and heterozygous Risk allele GG, CG had 4.37 fold risk of developing NAFLD than the homozygous wild type CC (CI 1.491-12.826, p &amp;lt; 0.005*) and by dominant analysis the risk G allele had 3.45 fold more risk of having NAFLD than the wild type C allele (CI 1.408-8.474, P-value &amp;lt;0.003*) in Egyptian Conclusion We demonstrated for the first time risk of PNPLA3 rs738409 polymorphism in Egyptian, by dominant analysis the risk G allele had 3.45 fold more risk of having NAFLD than the wild type C allele in Egyptian, the risk G allele had 4.19 fold more risk of having sheatohepatitis (NASH) than the wild type C allele among the studied NAFLD patients group.

NAFLD renaming to MAFLD, MASLD: background, similarities, differences, and countermeasures

Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic stress liver injury due to chronic malnutrition in genetically susceptible individuals. With the prevalence of obesity, diabetes, and metabolic syndrome, NAFLD has become the world's number one chronic liver disease, and the flaws of forty years of exclusive disease diagnostic criteria and stigmatized disease terminology are becoming increasingly prominent. To this end, in the past three years, the international consensus group and the three major hepatology societies have suggested that NAFLD be renamed metabolism-associated fatty liver disease (MAFLD) and metabolism-associated steatosis liver disease (MASLD). Here is a description of the background of naming NAFLD, MAFLD, and MASLD, the similarities and differences of the three terms, the existing disputes, and our country's coping strategies.

Kynurenine pathway dynamics in patients with schizophrenia spectrum disorders across the disease trajectory

The aim of this study was to evaluate how schizophrenia spectrum disorders (SSD) and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum levels of tryptophan (Trp) metabolites. A total of 112 adults (54 first-episode psychosis [FEP] patients and 58 control subjects [CSs]) participated in the study. The investigated changes in the metabolite levels appeared against a background of persistent increase in BMI and waist circumference among the patients. Regarding the kynurenine (KYN) pathway, the strongest changes were seen in AP-naïve FEP patients. Trp, KYN, kynurenic acid (KYNA), and anthranilic acid (ANT) levels were significantly reduced in blood samples from patients in the early stage of the disease. Furthermore, 3-OH-kynurenine (3-HK) and quinolinic acid (QUIN) levels were somewhat lower in these patients. Most of these changes in the KYN pathway became weaker with AP treatment. The levels of serotonin and its metabolite 5-HIAA tended to be higher at 5.1 years in patients showing the relation of elevated serotonin turnover to increased BMI and waist circumference. The similar trend was evident for the ratio between xanthurenic acid (XA) and KYNA with strong link to the elevated BMI. Altogether, the present study supports the role of Trp-metabolites in the development of obesity and metabolic syndrome in SSD patients.

A Clinical Study on the Efficiency of Homoeopathic Medicines in the Treatment of Gout with an Evaluation Based on Serum Uric Acid Level

Gout was first described by “Hippocrates". The term ‘gout’ is derived from Latin word ‘gutta’ and French word ‘gote’, both meaning a drop of liquid. Hundred years ago the gout was thought to be caused by drops of viscous humors that seeped from blood into the joints. It has been known as “the disease of kings” because of its association with the kind of over indulgence in food and wine, which only the rich and powerful could afford. Among the lengthy list of metabolic disease, gout is by far the most common one arising either from the enzymatic malfunctioning of purine synthesis or metabolism resulting in the over production of uric acid or else its poor clearance due to faulty performance of the kidneys. Gout is the most common inflammatory arthritis worldwide; gout and hyperuricemia are on the rise owing mainly to dietary changes, obesity, and metabolic syndrome and increased age. In the past two decades the prevalence of gout has doubled owing mostly to changes in diet. Keywords: Gout, Homoeopathy, Serum Uric Acid Level, Tophi, podagra

Adenosine Triphosphate Citrate Lyase and Fatty Acid Synthesis Inhibition

Adenosine triphosphate citrate lyase (ACLY) is a key regulatory enzyme of glucose metabolism, cholesterol and fatty acid synthesis, and the inflammatory cascade. Bempedoic acid, an ACLY inhibitor, significantly reduces atherogenic lipid markers, including low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, and apolipoprotein B. Additional effects of ACLY inhibition include antitumor growth; reduction of triglycerides and proinflammatory molecules such as high-sensitivity C-reactive protein; less insulin resistance; reduction of hepatic lipogenesis; and weight loss. While numerous ACLY inhibitors have been identified, most of the clinical data have focused on bempedoic acid. The Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) program was a series of phase 3 clinical trials that evaluated its effects on lipid parameters and safety, leading to US Food and Drug Administration approval in 2020. CLEAR Outcomes was a phase 3, double-blind, randomized, placebo-controlled trial in individuals with a history of statin intolerance, serum LDL-C level of 100 mg/dL or higher, and a history of, or at high risk for, cardiovascular disease. Bempedoic acid modestly reduced the primary 4-way cardiovascular composite end point as well as the individual components of myocardial infarction and coronary revascularization but did not reduce stroke, cardiovascular death, or all-cause mortality. Rates of gout and cholelithiasis were higher with bempedoic acid, and small increases in serum creatinine, uric acid, and hepatic-enzyme levels were also observed. ACLY inhibition with bempedoic acid has been established as a safe and effective therapy in high-risk patients who require further LDL-C lowering, particularly for those with a history of statin intolerance. The recently published CLEAR Outcomes trial revealed modest reductions in cardiovascular events with bempedoic acid, proportional to its LDL-C lowering, in high-risk individuals with statin intolerance and LDL-C levels of 100 mg/dL or higher. The additional effects of ACLY inhibition have prompted a more thorough search for novel ACLY inhibitors for conditions such as cancer, hypertriglyceridemia, chronic inflammation, type 2 diabetes, fatty liver disease, obesity, and metabolic syndrome. Similarly, therapies that reduce fatty acid synthesis are being explored for their use in cardiometabolic conditions.

Epigenetic Regulation in Lean Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), the most prominent cause of chronic liver disease worldwide, is a rapidly growing epidemic. It consists of a wide range of liver diseases, from steatosis to nonalcoholic steatohepatitis, and predisposes patients to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. NAFLD is strongly correlated with obesity; however, it has been extensively reported among lean/nonobese individuals in recent years. Although lean patients demonstrate a lower prevalence of diabetes mellitus, central obesity, dyslipidemia, hypertension, and metabolic syndrome, a percentage of these patients may develop steatohepatitis, advanced liver fibrosis, and cardiovascular disease, and have increased all-cause mortality. The pathophysiological mechanisms of lean NAFLD remain vague. Studies have reported that lean NAFLD demonstrates a close association with environmental factors, genetic predisposition, and epigenetic modifications. In this review, we aim to discuss and summarize the epigenetic mechanisms involved in lean NAFLD and to introduce the interaction between epigenetic patterns and genetic or non genetic factors. Several epigenetic mechanisms have been implicated in the regulation of lean NAFLD. These include DNA methylation, histone modifications, and noncoding-RNA-mediated gene regulation. Epigenetics is an area of special interest in the setting of lean NAFLD as it could provide new insights into the therapeutic options and noninvasive biomarkers that target this under-recognized and challenging disorder.

Parental and familial factors related to participation in a home-based physical activity intervention in children with obesity or Prader-Willi syndrome

BackgroundIncreasing physical activity (PA) participation is vital to promote the development of health behaviors in childhood. This study examined which parental and familial factors predicted completion of and compliance with a home-based family PA program in a cohort of families with a child with Prader-Willi syndrome (PWS; a rare disorder with obesity and developmental disability) or with obesity but with neurotypical development. MethodsParticipants (n = 105) were parents of children with PWS (n = 41) and parents of children with obesity but without PWS (n = 64). Parents completed a series of questionnaires documenting their demographic characteristics, self-efficacy, social support, and family environment (active-recreational orientation and cohesion). Relationships between these factors and intervention completion and compliance were evaluated using bivariate correlations and logistic regression (compliance) and multiple regression (completion) analyses with groups together and then separately if the child group was a significant predictor. ResultsNone of the variables of interest (marital status, employment, employed hours per week, self-efficacy, social support, and family environment) were significant predictors of intervention completion. Intervention compliance was negatively associated with parents working part-time and working full-time and positively associated with family cohesion (Model R2 = 0.107, F(3,100) = 4.011, p = .010). Child group was not a factor. ConclusionsCompliance with a 24-week family home-based PA intervention was related to fewer employment hours of the primary caregiver and family environment factors. Future interventions should consider how to reduce the intervention's burden in working parents along with strategies to foster family cohesion.

Endothelial Dysfunction and Cardiometabolic Risk Factors in Mexican American Adults: The Cameron County Hispanic Cohort

Endothelial dysfunction assessed by impaired brachial flow-mediated dilation (FMD) predicts incident cardiovascular disease (CVD). We have previously shown that clustering of diabetes mellitus, obesity, and metabolic syndrome in young Hispanic patients was associated with subclinical atherosclerosis. This study aimed to assess determinants of impaired FMD response (%FMD), an earlier marker of atherosclerosis, in a population-based sample of asymptomatic Mexican Americans. Cardiometabolic biomarkers and FMD were obtained from 960 Cameron County Hispanic Cohort participants. Gender-specific median values of %FMD were used to categorize participants into those with %FMD below or above the median. The sample was further stratified into those younger and older than 55years. Survey-weighted logistic regression analyses were conducted to evaluate the effects of cardiometabolic biomarkers on the %FMD groups. The low %FMD group was significantly older, had higher visceral adipose tissue, systolic blood pressure, or plasma glucose, and had metabolic syndrome compared with those in the high %FMD group. Multivariable-adjusted age-stratified logistic regression analyses showed that in older participants, male gender (odds ratio [OR]=2.4 [1.4 to 4.2]) and having hypertension (OR=2.3 [1.3 to 4.3]) or prediabetes mellitus (OR=3.4 [1.5 to 7.5]) remained significantly associated with odds of low %FMD. In younger participants, high low-density lipoprotein (OR=2.8 [1.6 to 4.9]) or having the metabolic syndrome (OR=1.9 [1.1 to 3.6]) were significantly associated with odds of low %FMD. In conclusion, we found age-dependent associations between cardiometabolic biomarkers and an FMD response below the gender-specific median in a sample composed of Mexican Americans without previous CVD. Targeting specific risk factors by age may mitigate progression to incident CVD in this high-risk racial disparity group.

Normal-Weight Obesity and Metabolic Syndrome in Korean Adults: A Population-Based Cross-Sectional Study.

The disadvantage of using body mass index (BMI) as an obesity diagnostic tool is that it cannot distinguish between fat mass and lean mass, which may understate the impact of obesity on metabolic complications. This population-based cross-sectional study aimed to investigate the relationship between normal-weight obesity (NWO) and metabolic syndrome in Korean adults aged 20 years (5962 males and 6558 females) who took part in the Korea National Health and Nutrition Examination Surveys from 2008 to 2011. NWO was defined as having a BMI of 18.5 to 24.9 kg/m2 and a body fat percentage of 26.0% in males or 36.0% in females. Metabolic syndrome (MetS) was defined using the revised National Cholesterol Education Program definition, with a Korean-specific waist circumference threshold of >90 cm for males and >85 cm for females. NWO males and females were 2.7 times (p < 0.001) and 1.9 times (p < 0.001) more likely to develop metabolic syndrome than normal-weight non-obese males and females, respectively. Additionally, NWO females were 1.3 times (p = 0.027) more likely to develop MetS even after adjustments for all measured covariates. The current findings of the study show that NWO is a proxy biomarker of MetS to be considered for early intervention.

Morbid Obesity Associated with Non-Alcoholic Fatty Liver Disease and Complicated by Severe Non-Cirrhotic Portal Hypertension: A Case Report from Rural Kenya

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and is closely linked with obesity and metabolic syndrome. Portal hypertension in NAFLD typically occurs in the cirrhotic phase of the disease and may present with esophageal varices, splenomegaly with splenic sequestration syndrome, ascites, and features of liver failure. However, recent experimental and clinical data show the occurrence of portal hypertension in NAFLD in the absence of fibrosis or cirrhosis. We present such a clinical case from rural Kenya in this study with the literature review that proposes novel mechanisms for such non-cirrhotic portal hypertension in NAFLD.

Obesity, Metabolic Syndrome, and Osteoarthritis-An Updated Review.

Metabolic syndrome (MetS), also called the 'deadly quartet' comprising obesity, diabetes, dyslipidemia, and hypertension, has been ascertained to have a causal role in the pathogenesis of osteoarthritis (OA). This review is aimed at discussing the current knowledge on the contribution of metabolic syndrome and its various components to OA pathogenesis and progression. Lately, an increased association identified between the various components of metabolic syndrome (obesity, diabetes, dyslipidemia, and hypertension) with OA has led to the identification of the 'metabolic phenotype' of OA. These metabolic perturbations alongside low-grade systemic inflammation have been identified to inflict detrimental effects upon multiple tissues of the joint including cartilage, bone, and synovium leading to complete joint failure in OA. Recent epidemiological and clinical findings affirm that adipokines significantly contribute to inflammation, tissue degradation, and OA pathogenesis mediated through multiple signaling pathways. OA is no longer perceived as just a 'wear and tear' disease and the involvement of the metabolic components in OA pathogenesis adds up to the complexity of the disease. Given the global surge in obesity and its allied metabolic perturbations, this review aims to throw light on the current knowledge on the pathophysiology of MetS-associated OA and the need to address MetS in the context of metabolic OA management. Better regulation of the constituent factors of MetS could be profitable in preventing MetS-associated OA. The identification of key roles for several metabolic regulators in OA pathogenesis has also opened up newer avenues in the recognition and development of novel therapeutic agents.

Effect of liraglutide on cardiometabolic profile and on bioelectrical impedance analysis in patients with obesity and metabolic syndrome

Metabolic syndrome (MetS) and obesity represent a public health problem worldwide. Bioelectrical impedance analysis (BIA) is a practical and effective way of evaluating body composition, especially abdominal fat. Liraglutide, a GLP-1 analog, reduces body weight and improves cardiometabolic parameters. In this prospective non-randomized intervention study, we evaluated the effect of 6 months of treatment with liraglutide (n = 57) on the clinical, laboratory and BIA findings of adult sex-stratified patients diagnosed with obesity and MetS, compared to a control group receiving sibutramine (n = 46). The groups were statistically similar with regard to the age of females (p = 0.852) and males (p = 0.657). Almost all anthropometric and BIA variables were higher in the treatment group than in the comparative group (p < 0.05). Abdominal circumference (AC) decreased significantly more in the treatment group. In males, body weight and fat mass also decreased (p < 0.05). Liraglutide treatment was associated with a greater reduction in trunk fat mass (FMT) (p < 0.05). AC and FMT were strongly correlated (rho = 0.531, p < 0.001) in the treatment group. In the multiple regression analysis, liraglutide treatment remained independently associated with FMT. Treatment with liraglutide for 6 months promoted weight loss, improved cardiometabolic and inflammatory parameters and led to a significant reduction in FMT correlated with AC in obese MetS patients of both sexes.

Predictive factors to estimate the severity of nonalcoholic fatty liver disease in candidates for Roux-en-Y gastric bypass

ObjectivesNon-alcoholic fatty liver disease (NAFLD) is related to obesity, insulin resistance, dyslipidemia, and metabolic syndrome. The increasing prevalence of NAFLD results in a significant number of patients manifesting chronic liver disease over time. The aim of this study was to analyze the predictive factors to estimate NAFLD severity in patients who are candidates for Roux-en-Y gastric bypass. MethodsThis descriptive observational study was conducted with 136 obese patients who were candidates for Roux-en-Y gastric bypass and had mild, moderate, or severe NAFLD. ResultsSevere NAFLD was more prevalent among the men (P = 0.007), and mild NAFLD was more prevalent among the women (P = 0.007). Hyperferritinemia was observed in the group with severe NAFLD (P = 0.01). Neck circumference and waist-to-height ratio were associated with an increased risk when comparing the groups with mild and severe NAFLD and those with moderate and severe NAFLD (P = 0.023 and P = 0.001, respectively); the alanine aminotransferase (ALT) and aspartate aminotransferase ratio values were >1 (P = 0.002) in the same comparisons. The regression analyses showed that an increase of 1 ng/mL in vitamin D reduced the chances of severe steatosis by 10% (P = 0.043), and an increase of 1 U/L ALT increased the chances of severe steatosis by 13% (P = 0.002). ConclusionHigh neck circumference and low waist-to-height ratio values, male sex, hyperferritinemia, increased serum ALT values, and decreased vitamin D levels were related to the risk for severe NAFLD.

Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: The Next Threat after Viral Hepatitis.

For many years, we have faced the complications of viral hepatitis and alcohol-related liver diseases such as cirrhosis, decompensation, portal hypertension, and hepatocellular carcinoma (HCC). Recently, we have seen a dynamic change in the field of hepatology. With the significant achievements in eradicating the hepatitis C virus by direct-acting antiviral agents and the rising epidemic of obesity, diabetes mellitus, and metabolic syndrome, there is a paradigm shift in the leading cause of liver cirrhosis and cancer to nonalcoholic fatty liver disease (NAFLD). Current data highlight the rapidly rising incidence of NAFLD-related HCC worldwide and expose the unseen part of the iceberg. In this review, we aim to update knowledge about the pathogenesis of NAFLD-induced HCC, surveillance difficulties, and promising disease markers. Molecular biomarkers, for example, may become a promising cornerstone for risk-stratified surveillance, early detection, and treatment selection for NAFLD-related HCC. Physicians can offer personalized and tailor-made clinical decisions for this unique patient subgroup.

Layer-Specific BTX-A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement.

The rising incidence of health-endangering obesity constantly calls for more effective treatments. Gastric intramural injection of botulinum neurotoxin A (BTX-A) as a new modality carries great promise yet inconsistent therapeutic efficacy. A layer-specific delivery strategy enabled by dissolving microneedles is hence pioneered to investigate the working site of BTX-A and the resulting therapeutic effects. The drug-loaded tips of the layer-specific gastric paralysis microneedles (LGP-MN) rapidly release and achieve uniform distribution of BTX-A within the designated gastric wall layers. In an obesity rat model, the LGP-MNs not only prove safer than conventional injection, but also demonstrate consistently better therapeutic effects with muscular layer delivery, including 16.23% weight loss (3.06-fold enhancement from conventional injection), 55.20% slower gastric emptying rate, improved liver steatosis, lowered blood lipids, and healthier gut microbiota. Further hormonal study reveals that the elevated production of stomach-derived glucagon-like peptide-1 due to the muscularis-targeting LGP-MN treatment is an important contributor to its unique glucose tolerance-improving effect. This study provides clear indication of the gastric muscularis as the most favorable working site of BTX-A for weight loss and metabolic improvement purposes, and meanwhile suggests that the LGP-MNs could serve as a novel clinical approach to treat obesity and metabolic syndromes.

Serum concentrations of BDNF in adolescents with metabolic syndrome: a case-control study between normal - BMI adolescents and adolescents with obesity

Brain-Derived Neurotrophic Factor (BDNF) has been linked to various conditions of the cardiovascular and nervous systems. Scarce data exist about the concentrations of BDNF in children and adolescents in relation with obesity and metabolic syndrome (MetS). The aim of this study was to examine the serum BDNF concentrations in adolescents with metabolic syndrome and according to their body mass index (BMI) status. This was a case-control study, assessing BDNF concentrations between adolescents with MetS (with obesity vs. normal-BMI), in relation to sex, anthropometric, metabolic and endocrine parameters. Participants included male and female adolescents, whose anthropometric and metabolic panel, as well as serum BDNF concentrations were measured. A total of 59 adolescents (obesity: 29; normal-BMI: 30) were included in the study. Increased serum BDNF concentrations were observed in MetS adolescents with obesity when compared with normal-BMI adolescents (p < 0.001). Males exhibited higher concentrations of BDNF than females (p = 0.045). The sample was further divided into four categories by sex and BMI status, with normal-BMI females exhibiting significantly lower BDNF concentrations than females and males with obesity(p = 0.005). In the entire study sample, serum BDNF concentrations correlated positively with BMI z-scores, however, this statistical significance was preserved only in the females of the sample. No statistical difference was observed between males of different BMI z-scores categories. Conclusion: Obesity appeared as a major factor for increased serum BDNF concentrations in adolescents with MetS (vs. normal-BMI), with a higher impact on BDNF concentrations in females than males.What is Known:• The brain-derived neurotrophic factor (BDNF) is involved in metabolic syndrome in adults but data in adolescents are scarce.What is New:• Obesity (vs. normal BMI) was a major factor for increased serum BDNF in adolescents with metabolic syndrome.• Obesity had a higher impact on BDNF concentrations in females than males with metabolic syndrome.