Analysis of correlations between gut microbiota, stool short chain fatty acids, calprotectin and cardiometabolic risk factors in postmenopausal women with obesity: a cross-sectional study.

BACKGROUND: Microbiota and its metabolites are known to regulate host metabolism. In cross-sectional study conducted in postmenopausal women we aimed to assess whether the microbiota, its metabolites and gut barrier integrity marker are correlated with cardiometabolic risk factors and if microbiota is different between obese and non-obese subjects. METHODS: We analysed the faecal microbiota of 56 obese, postmenopausal women by means of 16S rRNA analysis. Stool short chain fatty acids, calprotectin and anthropometric, physiological and biochemical parameters were correlates to microbiome analyses. RESULTS: Alpha-diversity was inversely correlated with lipopolysaccharide (Rho = - 0.43, FDR P (Q) = 0.004). Bray-Curtis distance based RDA revealed that visceral fat and waist circumference had a significant impact on metabolic potential (P = 0.003). Plasma glucose was positively correlated with the Coriobacteriaceae (Rho = 0.48, Q = 0.004) and its higher taxonomic ranks, up to phylum (Actinobacteria, Rho = 0.46, Q = 0.004). At the metabolic level, the strongest correlation was observed for the visceral fat (Q < 0.15), especially with the DENOVOPURINE2-PWY, PWY-841 and PWY0-162 pathways. Bacterial abundance was correlated with SCFAs, thus some microbiota-glucose relationships may be mediated by propionate, as indicated by the significant average causal mediation effect (ACME): Lachnospiraceae (ACME 1.25, 95%CI (0.10, 2.97), Firmicutes (ACME 1.28, 95%CI (0.23, 3.83)) and Tenericutes (ACME - 0.39, 95%CI (- 0.87, - 0.03)). There were significant differences in the distribution of phyla between this study and Qiita database (P < 0.0001). CONCLUSIONS: Microbiota composition and metabolic potential are associated with some CMRF and fecal SCFAs concentration in obese postmenopausal women. There is no unequivocal relationship between fecal SCFAs and the marker of intestinal barrier integrity and CMRF. Further studies with appropriately matched control groups are warranted to look for causality between SCFAs and CMRF.

Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney.

AIMS: Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. METHODS AND RESULTS: We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. CONCLUSION: Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.

Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics.

Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource. Surveying 42 nonrenal tissues from the Genotype-Tissue Expression project revealed that, for approximately a fifth of the replicated genes, the association with age was kidney-specific. Seventy-three percent of the replicated genes were associated with functional or histological parameters of age-related decline in kidney health, including glomerular filtration rate, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial narrowing. Common genetic variants in four of the age-related genes, namely LYG1, PPP1R3C, LTF and TSPYL5, correlated with the trajectory of age-related changes in their renal expression. Integrative analysis of genomic, epigenomic, and transcriptomic information revealed that the observed age-related decline in renal TSPYL5 expression was determined both genetically and epigenetically. Thus, this study revealed robust molecular signatures of the aging kidney and new regulatory mechanisms of age-related change in the kidney transcriptome.

Body Composition, Anthropometric Indices and Hydration Status of Obstructive Sleep Apnea Patients: Can Cachexia Coexist with Obesity?

The aim of this study was to elucidate body composition, anthropometric indices, and hydration status in obstructive sleep apnea (OSA) patients, taking into account different disease stages, gender, and the possibility of the presence of cachexia. There were 98 OSA patients and 23 control subjects enrolled into the study. All study participants underwent polysomnography examination. Body mass index (BMI), fat mass index (FMI), fat free mass, muscle mass, body cell mass, total body water, and extracellular and intracellular water were evaluated. The neck, abdominal, and waist circumference was measured. We found that overweight and obesity were present in 96% of patients. Cachexia was present in one OSA individual with comorbidities. Apnea-hypopnea index correlated with the neck and waist circumference, and with BMI in OSA patients. All muscle indices and water contents above outlined were significantly higher in severe OSA compared with control subjects. BMI, FMI, neck circumference, and extracellular water were greater in a subset of severe OSA compared with a moderate OSA stage. The female OSA patients had a higher FMI than that present in males at a comparable BMI. We conclude that the most body composition indices differed significantly between severe OSA patients and control subjects. A higher FMI in females at a comparable BMI could be due to a discordance between BMI and FMI. Cachexia occurs rarely in OSA and seems to coexist with comorbidities.

Effects of Endurance and Endurance-strength Exercise on Renal Function in Abdominally Obese Women with Renal Hyperfiltration: A Prospective Randomized Trial.

OBJECTIVE: Obesity is associated with kidney defects. Physical activity is a key element in the treatment of obesity. The aim of this study was to compare the effect of endurance and endurance-strength training on kidney function in abdominally obese women. METHODS: Forty-four abdominally obese women were randomized to endurance training or endurance-strength training, three times a week for 3 months. Before and after the intervention, kidney function was assessed by measuring blood creatinine, urine creatinine, and urine albumin levels, and the albumin-to-creatinine ratio and glomerular filtration rate (GFR) were calculated. RESULTS: Renal hyperperfusion was present in both groups before the study. Following both types of physical activity, similar modifications of the investigated parameters were observed, but with no significant between-group differences. Both courses of training led to a significant increase in blood creatinine and a subsequent decrease in the GFR. A significant increase in urine creatinine and album levels, though not exceeding the range for microalbuminuria, was not accompanied by any difference in the albumin-to-creatinine ratio after endurance-strength training alone. CONCLUSION: Three months of either endurance or endurance-strength training has a favorable and comparable effect on renal function in abdominally obese women with renal hyperfiltration.

Changes in mineral status are associated with improvements in insulin sensitivity in obese patients following L-arginine supplementation.

PURPOSE: The aim of this study is to evaluate the long-term influence of L-arginine intake on mineral concentration in patients with obesity and to assess the changes in lipid serum levels, fat content, and insulin resistance that result. METHODS: A randomized double-blind placebo-controlled study was conducted. 88 obese patients were randomly assigned to receive either 9 g of L-arginine or placebo daily, for 6 months. At baseline and after 6 months, selected anthropometrical measurements and blood biochemical analyses were performed and mineral levels were assessed. To assess insulin sensitivity, the gold-standard euglycemic clamp methodology was used. RESULTS: We found that 6 months of L-arginine supplementation resulted in significant increases in insulin sensitivity (Δ1.1 mg/kg/min, P < 0.01) and zinc levels (Δ1.5 µmol/L, P < 0.001). Moreover, a positive correlation between the change in zinc concentration in serum and the change in insulin sensitivity was observed (R = 0.80, P < 0.01). In the group of patients treated with L-arginine, a negative correlation between the change in zinc concentration in serum and the change in body fat content was noted (R = -0.38, P < 0.05). CONCLUSIONS: L-Arginine supplementation affects zinc status in obese patients. One beneficial influence is related to the improvements in insulin sensitivity.

Can Adipokine FAM19A5 Be a Biomarker of Metabolic Disorders?

Aim: One of the most critical functions of adipose tissue is the production of adipokines, ie, numerous active substances that regulate metabolism. One is the newly discovered FAM19A5, whose older name is TAFA-5. Purpose: The study aimed to review the literature on the FAM19A5 protein. Methods: The review was conducted in December 2023 using the PubMed (Medline) search engine. Sixty-four papers were included in the review. Results: This protein exhibits the characteristics of an adipokine with positive features for maintaining homeostasis. The results showed that FAM19A5 was highly expressed in adipose tissue, with mild to moderate expression in the brain and ovary. FAM19A5 may also inhibit vascular smooth muscle cell proliferation and migration through the perivascular adipose tissue paracrine pathway. Serum levels of FAM19A5 were decreased in obese children compared with healthy controls. There are negative correlations between FAM19A5, body mass index, and fasting insulin. Serum FAM19A5 level is correlated with type 2 diabetes, waist circumference, waist-to-hip ratio, glutamic pyruvic transferase, fasting plasma glucose, HbA1c, and mean shoulder pulse wave velocity. FAM19A5 expression was reduced in mice with obesity. However, the data available needs to be clarified or contradictory. Conclusion: Considering today's knowledge about FAM19A5, we cannot consider this protein as a biomarker of the metabolic syndrome. According to current knowledge, FAM19A5 cannot be considered a marker of metabolic disorders because the results of studies conducted in this area are unclear.

Effects of 12-Week Combined Strength and Endurance Circuit Training Program on Insulin Sensitivity and Retinol-Binding Protein 4 in Women with Insulin-Resistance and Overweight or Mild Obesity: A Randomized Controlled Trial.

Background: Circuit training is an exercise mode, that may include both endurance and resistance components. There are premises that a combination of these two modalities brings additional benefits, particularly in improving insulin sensitivity. The retinol-binding protein 4 (RBP4) may inhibit signaling from insulin metabolic pathways in skeletal muscles, thus developing insulin resistance. This study aimed to evaluate whether moderate intensity circuit training combining strength and endurance exercise induces changes in tissue insulin sensitivity, carbohydrate and lipid metabolism, and serum RBP4 levels in insulin-resistant women. Methods: In this clinical controlled trial women diagnosed with insulin-resistance were randomly divided into two groups. The training group (T) performed circuit training combining strength (50%-80%1RM) and endurance (50%-75%HRR) exercise on five weight and two cardio machines, for 33 minutes, three times per week, for 3 months. Women from the control non-training group (NT) did not change their previous physical activity. At the beginning of the study and after the intervention period, a one-repetition maximum, body mass, and composition, resting heart rate (HR), blood pressure, glucose, insulin, blood lipids, thyroid-stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1), RBP4, and insulin resistance (HOMA-IR) were measured. The results of 27 patients were analyzed using a two-way repeated measures ANOVA. Results: Significant differences in the pattern of change over time between the groups for resting HR (p < 0.010) and total lean mass (p < 0.039) were found. No differences in HOMA-IR, and RBP4 were observed post-study compared to pre-study in the T group. A significant correlation between RBP4 and TSH concentration was found. Conclusion: Twelve-week circuit training combining strength and endurance exercise has minor effects on HOMA-IR, glucose and lipid metabolism, IGF-1, TSH, and RBP4. Although moderate-intensity circuit training is considered safe, its effectiveness in patients with overweight and mild obesity may be insufficient to reduce insulin resistance. Trial Registration: ClinicalTrials.gov: NCT04528693, registered August 23, 2020.

Genotypes of the UCP1 gene polymorphisms and cardiometabolic diseases: A multifactorial study of association with disease probability.

Cardiometabolic diseases (CMDs) are complex disorders with a heterogenous phenotype, which are caused by multiple factors including genetic factors. Single nucleotide polymorphisms (SNPs) rs45539933 (p.Ala64Thr), rs10011540 (c.-112A>C), rs3811791 (c.-1766A>G), and rs1800592 (c.-3826A>G) in the UCP1 gene have been analyzed for association with CMDs in many studies providing controversial results. However, previous studies only considered individual UCP1 SNPs and did not evaluate them in an integrated manner, which is a more powerful approach to uncover genetic component of complex diseases. This study aimed to investigate associations between UCP1 genotype combinations and CMDs or CMD risk factors in the context of non-genetic factors. We performed multiple logistic regression analysis and proposed new methodology of testing different combinations of SNP genotypes. We found that probability of CMDs increased in presence of the three-SNP combination of genotypes with minor alleles of c.-3826A>G and p.Ala64Thr and wild allele of c.-112A>C, with increasing age, body mass index (BMI), body fat percentage (BF%) and may differ between sexes and between countries. The combination of genotypes with c.-3826A>G minor allele and wild homozygotes of c.-112A>C and p.Ala64Thr was associated with increased probability of diabetes. While combination of genotypes with minor alleles of all three SNPs reduced the CMD probability. The present results suggest that age, BMI, sex, and UCP1 three-SNP combinations of genotypes significantly contribute to CMD probability. Varying of c.-112A>C alleles in the genotype combination with minor alleles of c.-3826A>G and p.Ala64Thr markedly changes CMD probability.

Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.

Multispecies probiotic affects fecal short-chain fatty acids in postmenopausal women with obesity: A post hoc analysis of a randomized, double-blind, placebo-controlled study.

OBJECTIVES: Probiotics are known to regulate host metabolism. The aim of this study was to assess whether interventions with a multi-strain probiotic formula affect fecal short-chain fatty acids (SCFAs). METHODS: The analysis was carried out in 56 obese, postmenopausal women randomized to three groups: probiotic dose 2.5 × 109 CFU/d (n = 18; lower probiotic dose [LPD]), 1 × 1010 CFU/d (n = 18; higher probiotic dose [HPD]), or placebo (n = 20). RESULTS: An increase in three SCFA fecal concentrations in the HPD group was observed: acetic acid (C2; effect [E] = 1.72, SE = 0.73; 95% confidence interval [CI], 0.28-3.16; P = 0.019), butyric acid (C4; E = 0.98, SE = 0.46; 95% CI, 0.08-1.88; P = 0.033), and valeric acid (C5; E = 0.68, SE = 0.23; 95% CI, 0.23-1.12; P = 0.003). The mediation analysis showed that the decrease in uric acid under HPD may be transmitted through the elevation of C5 content. Multi-strain probiotic increases the SCFA content in the stool in a dose-dependent manner, which may diminish some cardiovascular risk factors because of a reduction in blood uric acid levels. CONCLUSION: Assessing long-term health benefits requires further research, including assessment of blood SCFA concentrations and multiomic and mechanistic approaches.

Association of Serum Vaspin Concentration with Metabolic Disorders in Obese Individuals.

Vaspin, a molecule produced in visceral adipose tissue, seems to participate in the pathogenesis of metabolic disorders. The study aimed to determine the association of vaspin concentration with metabolic disorders in obese individuals. Forty obese patients and twenty normal-weight subjects underwent biochemical (fasting glucose, insulin, lipid profile, interleukin-6, hs-CRP, vaspin concentration), blood pressure, and anthropometric measurements. The HOMA-IR index was calculated. Serum vaspin concentrations in the obese group were significantly higher than in the control group (0.82 ± 0.62 vs. 0.43 ± 0.59; p < 0.001). Among the entire population, vaspin concentration was positively correlated with body weight, BMI, WHR, and the percentage and mass of adipose tissue. Positive correlations between vaspin concentration and triglyceride level, insulin concentration, and HOMA-IR value were found. Vaspin concentration was positively correlated with hs-CRP and IL-6 levels. In obese patients, positive correlations between vaspin concentration and the percentage of adipose tissue and hs-CRP level were demonstrated. Logistic regression analysis showed that increased BMI was the biggest factor stimulating vaspin concentrations (OR = 8.5; 95% CI: 1.18-61.35; p = 0.0338). An elevated vaspin level may imply its compensatory role against metabolic disorders in obese patients. Thus, vaspin appears to be a useful diagnostic parameter for new therapeutic approaches in obesity-related complications. Nevertheless, due to the small sample size, further studies are needed to confirm our results.

NGS Sequencing Reveals New UCP1 Gene Variants Potentially Associated with MetS and/or T2DM Risk in the Polish Population-A Preliminary Study.

The number of people suffering from metabolic syndrome (MetS) including type 2 diabetes (T2DM), hypertension, and obesity increased over 10 times through the last 30 years and it is a severe public health concern worldwide. Uncoupling protein 1 (UCP1) is a mitochondrial carrier protein found only in brown adipose tissue involved in thermogenesis and energy expenditure. Several studies showed an association between UCP1 variants and the susceptibility to MetS, T2DM, and/or obesity in various populations; all these studies were, however, limited to a few selected polymorphisms. The present study aimed to search within the entire UCP1 gene for new variants potentially associated with MetS and/or T2DM risk. We performed NGS sequencing of the entire UCP1 gene in 59 MetS patients including 29 T2DM patients, and 36 controls using the MiSeq platform. An analysis of allele and genotype distribution revealed nine variations which seem to be interesting in the context of MetS and fifteen in the context of T2DM. Altogether, we identified 12 new variants, among which only rs3811787 was investigated previously by others. Thereby, NGS sequencing revealed new intriguing UCP1 gene variants potentially associated with MetS and/or T2DM risk in the Polish population.

Berberine in Non-Alcoholic Fatty Liver Disease-A Review.

The incidence of Non-Alcoholic Fatty Liver Disease (NAFLD) has been rapidly increasing during the last decade. It is a relevant health problem that affects 25% of the general population. NAFLD involves an extensive array of clinical conditions. So far, no approved pharmacological therapy for NAFLD has been developed. Multiple bioactive compounds have been proposed to treat NAFLD. One of the most promising is Berberine (BBR). Its pleiotropic effect positively impacts various cardiometabolic aspects. In this review, we summarize NAFLD, its metabolic and cardiovascular complications, the hepatoprotective effects of BBR due to its broad spectrum of pharmacological effects, and the potential role of BBR in NAFLD therapy. BBR ameliorates NAFLD by affecting numerous abnormalities. It inhibits lipogenesis and gluconeogenesis, improves insulin resistance and lipid profile, and modulates gut microbiota. The exact mechanism underlying these effects is not yet entirely explained. A growing amount of evidence confirming the positive effects of BBR on multiple metabolic pathways, such as lipids and glucose metabolism, energy homeostasis, or gut microbiota modulation, allows us to speculate about the importance of this natural bioactive substance for NAFLD therapy.

The Relation between Resistin (-420C/G) Single Nucleotide Variant, Resistin Serum Concentration, Carbohydrate, and Lipid Parameters and Fried Food Taste Preference in Patients with Hypertriglyceridemia.

BACKGROUND: Resistin is a proinflammatory adipokine involved in metabolic disorders. Its interplay with hypertriglyceridemia remains to be elucidated. We aimed to evaluate the relationship between resistin (-420C/G) single nucleotide variant (SNV) and metabolic parameters and preference for fried food consumption in hypertriglyceridemia. METHODS: The study enrolled 179 hypertriglyceridemic (HTG) and 182 normotriglyceridemic (NTG) patients. Anthropometric measurements, serum resistin, insulin and fasting glucose concentration, a homeostatic model assessment-insulin resistance (HOMA-IR), triglycerides (TG), cholesterol concentration, and fried food taste preference (FP) or other cooking methods preference (OP) were assessed in the study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: HTG and NTG groups did not differ significantly in serum resistin concentration; HTG individuals demonstrated significantly increased serum levels of TG, glucose, total cholesterol (TCH), and HOMA-IR and decreased HDL cholesterol. Resistin, insulin, glucose, HOMA-IR, and cholesterol fractions were similar among particular resistin genotypes in HTG, NTG, FP, or OP groups. TG and TCH concentrations differ significantly among CG and CC genotypes in the FP group. Considering the FP group, GG and CG genotypes appeared more frequently in hyperlipidemic (OR 2.6 95% CI; 1.16-5.82; p = 0.01; significant after Bonferroni correction) than in NTG patients. Multivariable logistic regression models showed that the G allele and CG genotype of SNV (-420C/G), adjusted for selected confounders such as fried food preference, increased the odds of hypertriglyceridemia about twofold. CONCLUSIONS: Allele G and CG genotype of resistin SNV (-420C/G) are linked with the preference for fried food taste in hypertriglyceridemic patients.

Treatment With Multi-Species Probiotics Changes the Functions, Not the Composition of Gut Microbiota in Postmenopausal Women With Obesity: A Randomized, Double-Blind, Placebo-Controlled Study.

Probiotics are known to regulate host metabolism. In randomized controlled trial we aimed to assess whether interventions with probiotic containing following strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus casei W56, Ligilactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58 affect gut microbiota to promote metabolic effects. By 16S rRNA sequencing we analyzed the fecal microbiota of 56 obese, postmenopausal women randomized into three groups: (1) probiotic dose 2.5 × 109 CFU/day (n = 18), (2) 1 × 1010 CFU/day (n = 18), or (3) placebo (n = 20). In the set of linear mixed-effects models, the interaction between pre- or post-treatment bacterial abundance and time on cardiometabolic parameters was significantly (FDR-adjusted) modified by type of intervention (26 and 19 three-way interactions for the pre-treatment and post-treatment abundance, respectively), indicating the modification of the bio-physiological role of microbiota by probiotics. For example, the unfavorable effects of Erysipelotrichi, Erysipelotrichales, and Erysipelotrichaceae on BMI might be reversed, but the beneficial effect of Betaproteobacteria on BMI was diminished by probiotic treatment. Proinflammatory effect of Bacteroidaceae was alleviated by probiotic administration. However, probiotics did not affect the microbiota composition, and none of the baseline microbiota-related features could predict therapeutic response as defined by cluster analysis. Conclusions: Probiotic intervention alters the influence of microbiota on biochemical, physiological and immunological parameters, but it does not affect diversity and taxonomic composition. Baseline microbiota is not a predictor of therapeutic response to a multispecies probiotic. Further multi-omic and mechanistic studies performed on the bigger cohort of patients are needed to elucidate the cardiometabolic effect of investigated probiotics in postmenopausal obesity.

Prevalence of uncoupling protein one genetic polymorphisms and their relationship with cardiovascular and metabolic health.

Contribution of UCP1 single nucleotide polymorphisms (SNPs) to susceptibility for cardiometabolic pathologies (CMP) and their involvement in specific risk factors for these conditions varies across populations. We tested whether UCP1 SNPs A-3826G, A-1766G, Ala64Thr and A-112C are associated with common CMP and their risk factors across Armenia, Greece, Poland, Russia and United Kingdom. This case-control study included genotyping of these SNPs, from 2,283 Caucasians. Results were extended via systematic review and meta-analysis. In Armenia, GA genotype and A allele of Ala64Thr displayed ~2-fold higher risk for CMP compared to GG genotype and G allele, respectively (p<0.05). In Greece, A allele of Ala64Thr decreased risk of CMP by 39%. Healthy individuals with A-3826G GG genotype and carriers of mutant allele of A-112C and Ala64Thr had higher body mass index compared to those carrying other alleles. In healthy Polish, higher waist-to-hip ratio (WHR) was observed in heterozygotes A-3826G compared to AA homozygotes. Heterozygosity of A-112C and Ala64Thr SNPs was related to lower WHR in CMP individuals compared to wild type homozygotes (p<0.05). Meta-analysis showed no statistically significant odds-ratios across our SNPs (p>0.05). Concluding, the studied SNPs could be associated with the most common CMP and their risk factors in some populations.

Nutritional Approach Targeting Gut Microbiota in NAFLD-To Date.

Non-alcoholic fatty liver disease (NAFLD) is a significant clinical and epidemiological problem that affects around 25% of the adult global population. A large body of clinical evidence highlights that NAFLD is associated with increased liver-related morbidity and mortality and an increased risk of cardiovascular disease, extrahepatic cancers, type 2 diabetes, and chronic kidney disease. Recently, a series of studies revealed the pivotal role of gut microbiota (GM) dysbiosis in NAFLD's pathogenesis. The GM plays an essential role in different metabolic pathways, including the fermentation of diet polysaccharides, energy harvest, choline regulation, and bile acid metabolism. One of the most critical factors in GM stabilization is the diet; therefore, nutritional therapyappearsto be a promising tool in NAFLD therapy. This paper aims to review the current knowledge regardingthe nutritional approach and its implications with GM and NAFLD treatment. We discuss the positive impact of probiotics, prebiotics, and symbiotics in a reverse dysbiosis state in NAFLD and show the potential beneficial effects of bioactive substances from the diet. The full description of the mechanism of action and comprehensive examination of the impact of nutritional interventions on GM modulation may, in the future, be a simple but essential tool supporting NAFLD therapy.

The effect of endurance and endurance-strength training on body composition and cardiometabolic markers in abdominally obese women: a randomised trial.

Studies comparing the effect of endurance and endurance-strength training on cardiometabolic markers provided inconsistent results. Therefore, the study aimed to compare the effect of endurance and endurance-strength training on body composition and cardiometabolic parameters in abdominally obese women. In this randomised trial, 101 subjects were included and divided into endurance (n = 52) and endurance-strength (n = 49) training. During the 12-week intervention, participants performed supervised one-hour training three times a week. Body composition, blood pressure (BP), markers of glucose and lipid homeostasis, and myoglobin levels were measured before and after the intervention. In total, 85 subjects completed the trial. Both interventions decreased fat mass and visceral adipose tissue and increased free fat mass, appendicular lean mass index and lean mass index. Neither endurance training nor endurance-strength training affected glucose and lipid metabolism. However, only endurance training significantly decreased paraoxonase and myoglobin levels. Both training programmes significantly decreased BP, with a more reduction of diastolic BP noted in the endurance group. In conclusion, both training programmes had a favourable effect on body composition but did not improve glucose and lipid homeostasis. Besides, endurance training decreased paraoxonase activity and myoglobin levels and was more effective in reducing BP.The study was registered with the German Clinical Trials Register (DRKS) within the number: DRKS00019832 (retrospective registration), date of registration: 26/02/2020.

Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney.

The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.