IA-Body Composition CT at T12 in Idiopathic Pulmonary Fibrosis: Diagnosing Sarcopenia and Correlating with Other Morphofunctional Assessment Techniques.

BACKGROUND: Body composition (BC) techniques, including bioelectrical impedance analysis (BIVA), nutritional ultrasound® (NU), and computed tomography (CT), can detect nutritional diagnoses such as sarcopenia (Sc). Sc in idiopathic pulmonary fibrosis (IPF) is associated with greater severity and lower survival. Our aim was to explore the correlation of BIVA, NU and functional parameters with BC at T12 level CT scans in patients with IPF but also its relationship with degree of Sc, malnutrition and mortality. METHODS: This bicentric cross-sectional study included 60 IPF patients (85.2% male, 70.9 ± 7.8 years). Morphofunctional assessment (MFA) techniques included BIVA, NU, CT at T12 level (T12-CT), handgrip strength, and timed up and go. CT data were obtained using FocusedON®. Statistical analysis was conducted using JAMOVI version 2.3.22 to determine the cutoff points for Sc in T12-CT and to analyze correlations with other MFA techniques. RESULTS: the cutoff for muscle area in T12-CT was ≤77.44 cm2 (area under the curve (AUC) = 0.734, sensitivity = 41.7%, specificity = 100%). The skeletal muscle index (SMI_T12CT) cutoff was ≤24.5 cm2/m2 (AUC = 0.689, sensitivity = 66.7%, specificity = 66.7%). Low SMI_T12CT exhibited significantly reduced median survival and higher risk of mortality compared to those with normal muscle mass (SMI cut off ≥ 28.8 cm/m2). SMI_T12CT was highly correlated with body cell mass from BIVA (r = 0.681) and rectus femoris cross-sectional area (RF-CSA) from NU (r = 0.599). Cronbach's α for muscle parameters across different MFA techniques and CT was 0.735, confirming their validity for evaluating muscle composition. CONCLUSIONS: T12-CT scan is a reliable technique for measuring low muscle mass in patients with IPF, specifically when the L3 vertebrae are not captured. An SMI value of <28.8 is a good predictor of low lean mass and 12-month mortality in IPF patients.

Differential Ophthalmological Profile in Patients with Coronary Artery Disease Coexisting with Type 2 Diabetes Mellitus: Elevated Tear Cytokine Concentrations.

Background/Objectives: Coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) are characterized by chronic low-grade inflammation. However, measuring cytokines typically involves invasive blood sampling, which can be problematic for CAD patients. This study aimed to assess ophthalmological parameters and tear cytokines in patients with CAD, comparing those with comorbid T2DM to those without to understand their inflammatory profiles. Methods: One hundred subjects with suspected chronic or acute CAD were initially included in this single-center cross-sectional study after clinical stabilization. Seventy-two patients with confirmed CAD were divided into two groups: 32 patients with T2DM and 40 patients without T2DM. A total of 144 eyes were examined, and tear fluid samples were collected to determine cytokine concentrations. Ophthalmological parameters and tear concentrations of cytokines were analyzed, controlling for age, sex, and other cardiovascular risk factors. Results: Patients with CAD and T2DM exhibited decreased ophthalmological parameters and increased cytokine concentrations in comparison to those without T2DM. Significant inverse correlations between ophthalmological parameters and cytokine concentrations were observed. Following adjustment, a full logistic regression model for distinguishing patients with CAD and comorbid T2DM included macular cube volume, mean macular thickness, interleukin (IL)-4, IL-5, IL-6, IL-8, IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), CCL3, CCL4, and CCL11/eotaxin-1, demonstrating excellent discriminatory power (Area Under the Curve = 0.95, 95% Confidence Interval = 0.91-0.99; p < 0.001). Subsequently, IL-5 (Odds Ratio = 1.68, 95% CI = 1.26-2.24; p < 0.001), G-CSF (OR = 1.06, 95% CI = 1.02-1.11; p < 0.01), and CCL11/eotaxin-1 (OR = 1.56, 95% CI = 1.19-2.05; p = 0.001) emerged as the most distinguishing variables in a reduced model (AUC = 0.89, 95% CI = 0.84-0.95; p < 0.001). Conclusions: Differences in ophthalmological variables, mainly in cytokine concentrations, suggest distinct pathophysiological mechanisms in patients with CAD based on the presence of T2DM. These findings demonstrate that the inflammatory profile can be readily detected through tear sample cytokines, proving valuable for establishing more accurate prognoses and monitoring in cardiometabolic disorders.

Effects of the Ketogenic Diet on Strength Performance in Trained Men and Women: A Systematic Review and Meta-Analysis.

Ketogenic diets (KDs) are an alternative to improve strength performance and body composition in resistance training participants. The objective of this review and meta-analysis is to verify whether a ketogenic diet produces an increase in the strength of resistance-trained participants. We have evaluated the effect of the ketogenic diet in conjunction with resistance training on the strength levels in trained participants. Boolean algorithms from various databases (PubMed, Scopus, and Web of Science) were used. Meta-analyses were carried out, one on the 1-RM squat (SQ), with 106 trained participants or athletes, and another on the 1-RM on the bench press (BP), evaluating 119 participants. We did not find significant differences between the groups in the variables of SQ or BP, although the size of the effect was slightly higher in the ketogenic group. Conclusions: KDs do not appear to impair 1-RM performance; however, this test does not appear to be the most optimal tool for assessing hypertrophy-based strength session performance in resistance-trained participants.

Physical activity shifts gut microbiota structure in aged subjects with overweight/obesity and metabolic syndrome.

We aimed to identify how physical activity (PA), within the context of a Mediterranean diet, affects metabolic variables and gut microbiota in older individuals with overweight/obesity and metabolic syndrome. Observational analysis was conducted as part of the PREDIMED-Plus study with 152 males and 145 females with overweight/obesity and metabolic syndrome. General assessments, anthropometric and biochemical measurements, and gut microbial 16S rRNA sequencing data were analyzed at baseline and 1-year of follow-up. Participants were stratified by tertiles of 1-year change in total PA-related energy expenditure ranging from -98.77 to 1099.99 METs (min/week). The total PA percentage of change was reduced in tertile 1 (-44.83 ± 24.94), increased in tertile 2 (28.96 ± 23.33) and tertile 3 (273.64 ± 221.42). Beta diversity analysis showed differences in the gut microbiota population within each tertile group. Significant differences were found at phylum, family, and genus levels in the gut microbiota of the three tertile groups at baseline and 1-year timepoint. Tertile 3, the group with the greatest increase in PA, was characterized by increases in their levels of Sutterella, Bilophila, and Lachnospira bacteria as well as a reduction in Collinsella. Moreover, this tertile showed a different pattern in its predicted metabolic capacities to the other groups. Our results have demonstrated that changes in PA such as lifestyle and Mediterranean diet induces specific variations in the gut microbiota profile. This modulation of gut microbiome populations and their metabolic capacities may contribute to the health of the aged individuals with overweight/obesity and metabolic syndrome.

A Systematic Review of Proteomics in Obesity: Unpacking the Molecular Puzzle.

PURPOSE OF REVIEW: The present study aims to review the existing literature to identify pathophysiological proteins in obesity by conducting a systematic review of proteomics studies. Proteomics may reveal the mechanisms of obesity development and clarify the links between obesity and related diseases, improving our comprehension of obesity and its clinical implications. RECENT FINDINGS: Most of the molecular events implicated in obesity development remain incomplete. Proteomics stands as a powerful tool for elucidating the intricate interactions among proteins in the context of obesity. This methodology has the potential to identify proteins involved in pathological processes and to evaluate changes in protein abundance during obesity development, contributing to the identification of early disease predisposition, monitoring the effectiveness of interventions and improving disease management overall. Despite many non-targeted proteomic studies exploring obesity, a comprehensive and up-to-date systematic review of the molecular events implicated in obesity development is lacking. The lack of such a review presents a significant challenge for researchers trying to interpret the existing literature. This systematic review was conducted following the PRISMA guidelines and included sixteen human proteomic studies, each of which delineated proteins exhibiting significant alterations in obesity. A total of 41 proteins were reported to be altered in obesity by at least two or more studies. These proteins were involved in metabolic pathways, oxidative stress responses, inflammatory processes, protein folding, coagulation, as well as structure/cytoskeleton. Many of the identified proteomic biomarkers of obesity have also been reported to be dysregulated in obesity-related disease. Among them, seven proteins, which belong to metabolic pathways (aldehyde dehydrogenase and apolipoprotein A1), the chaperone family (albumin, heat shock protein beta 1, protein disulfide-isomerase A3) and oxidative stress and inflammation proteins (catalase and complement C3), could potentially serve as biomarkers for the progression of obesity and the development of comorbidities, contributing to personalized medicine in the field of obesity. Our systematic review in proteomics represents a substantial step forward in unravelling the complexities of protein alterations associated with obesity. It provides valuable insights into the pathophysiological mechanisms underlying obesity, thereby opening avenues for the discovery of potential biomarkers and the development of personalized medicine in obesity.

Rectus Femoris Cross-Sectional Area and Phase Angle asPredictors of 12-Month Mortality in Idiopathic Pulmonary Fibrosis Patients.

BACKGROUND: The value of the phase angle (PhA), measured via bioelectrical impedance analysis (BIA), could be considered a good marker of the cell mass and the cell damage of a patient; however, there are new techniques, such as muscle ultrasonography, that allow the quantity and quality of muscle to be assessed in a minimally invasive way. The aim of this study is to determine the prognostic value of morphofunctional techniques in the prognosis of mortality in patients with idiopathic pulmonary fibrosis (IPF). METHODS: This multicenter, cross-sectional study included 86 patients with idiopathic pulmonary fibrosis with a mean age of 71 years, 82.7% of whom were male. The nutritional risk of the patients was assessed by means of questionnaires, such as the Subjective Global Assessment (SGA), and non-invasive functional techniques, including BIA, nutritional ultrasound, and hand grip strength (HGS). Statistical analysis of the sample was performed using JAMOVI version 2.3.22. RESULTS: Correlations were made between the RF-CSA techniques with PhA (r = 0.48, p < 0.001), BCM (r = 0.70, p < 0.001), SMI (r = 0.64, p < 0.001), and HGS (r = 0.54, p < 0.001). The cut-off points for 12-month mortality were PhA = 4.5° (AUC = 0.722, sensitivity of 72.7% and specificity of 66.6%), BCM = 28.8 kg (AUC = 0.609, sensitivity of 32.4% and specificity of 100.0%), RF-CSA = 3.00 cm2 (AUC = 0.857, sensitivity of 64.4% and specificity of 100.0%), 6MMW = 420 m (AUC = 0.830, sensitivity of 63.27% and specificity of 100.0%), and TUG = 7.2 s (AUC = 0.771, sensitivity of 100.0% and specificity of 56.67%). In addition, a multivariate analysis was performed with RF-CSA, HR = 8.11 (1.39-47.16, p = 0.020), and PhA of 6.35 (1.29-31.15, p = 0.023), taking into account age, sex, and BMI to determine mortality. Finally, a Kaplan-Meier survival analysis was conducted with low or normal values for classical parameters (GAP and T6MM) and new parameters (PhA, BCM, RF-CSA, and TUG). CONCLUSION: RF-CSA and PhA were shown to be good prognostic markers of 12-month mortality and could, therefore, be useful screening tools to complement the nutritional assessment of IPF patients.

Multi-Omics Approach Reveals Prebiotic and Potential Antioxidant Effects of Essential Oils from the Mediterranean Diet on Cardiometabolic Disorder Using Humanized Gnotobiotic Mice.

Essential oils sourced from herbs commonly used in the Mediterranean diet have demonstrated advantageous attributes as nutraceuticals and prebiotics within a model of severe cardiometabolic disorder. The primary objective of this study was to assess the influences exerted by essential oils derived from thyme (Thymus vulgaris) and oregano (Origanum vulgare) via a comprehensive multi-omics approach within a gnotobiotic murine model featuring colonic microbiota acquired from patients diagnosed with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM). Our findings demonstrated prebiotic and potential antioxidant effects elicited by these essential oils. We observed a substantial increase in the relative abundance of the Lactobacillus genus in the gut microbiota, accompanied by higher levels of short-chain fatty acids and a reduction in trimethylamine N-oxide levels and protein oxidation in the plasma. Moreover, functional enrichment analysis of the cardiac tissue proteome unveiled an over-representation of pathways related to mitochondrial function, oxidative stress, and cardiac contraction. These findings provide compelling evidence of the prebiotic and antioxidant actions of thyme- and oregano-derived essential oils, which extend to cardiac function. These results encourage further investigation into the promising utility of essential oils derived from herbs commonly used in the Mediterranean diet as potential nutraceutical interventions for mitigating chronic diseases linked to CAD and T2DM.

Effects of exercise timing on metabolic health.

The increasing prevalence of metabolic syndrome is associated with major health and socioeconomic consequences. Currently, physical exercise, together with dietary interventions, is the mainstay of the treatment of obesity and related metabolic complications. Although exercise training includes different modalities, with variable intensity, duration, volume, or frequency, which may have a distinct impact on several characteristics related to metabolic syndrome, the potential effects of exercise timing on metabolic health are yet to be fully elucidated. Remarkably, promising results with regard to this topic have been reported in the last few years. Similar to other time-based interventions, including nutritional therapy or drug administration, time-of-day-based exercise may become a useful approach for the management of metabolic disorders. In this article, we review the role of exercise timing in metabolic health and discuss the potential mechanisms that could drive the metabolic-related benefits of physical exercise performed in a time-dependent manner.

Evaluation of Adipose Tissue Zinc-Alpha 2-Glycoprotein Gene Expression and Its Relationship with Metabolic Status and Bariatric Surgery Outcomes in Patients with Class III Obesity.

Zinc-α2 glycoprotein (ZAG) is an adipokine involved in adipocyte metabolism with potential implications in the pathogenesis of metabolic disorders. Our aim was to evaluate the relationship between visceral (VAT) and subcutaneous adipose tissue (SAT) ZAG expression and metabolic parameters in patients with class III obesity, along with the impact of basal ZAG expression on short- and medium-term outcomes related to bariatric surgery. 41 patients with class III obesity who underwent bariatric surgery were included in this study. ZAG gene expression was quantified in SAT and VAT. Patients were classified into two groups according to SAT and VAT ZAG percentile. Anthropometric and biochemical variables were obtained before and 15 days, 45 days, and 1 year after surgery. The lower basal SAT ZAG expression percentile was associated with higher weight and waist circumference, while the lower basal VAT ZAG expression percentile was associated with higher weight, waist circumference, insulin, insulin resistance, and the presence of metabolic syndrome. Basal SAT ZAG expression was inversely related to weight loss at 45 days after surgery, whereas no associations were found between basal VAT ZAG expression and weight loss after surgery. Additionally, a negative association was observed between basal SAT and VAT ZAG expression and the decrease of gamma-glutamyl transferase after bariatric surgery. Therefore, lower SAT and VAT ZAG expression levels were associated with an adverse metabolic profile. However, this fact did not seem to confer worse bariatric surgery-related outcomes. Further research is needed to assess the clinical significance of the role of ZAG expression levels in the dynamics of hepatic enzymes after bariatric surgery.

The Effect of Sex and Obesity on the Gene Expression of Lipid Flippases in Adipose Tissue.

Molecular mechanisms behind obesity and sex-related effects in adipose tissue remain elusive. During adipocyte expansion, adipocytes undergo drastic remodelling of lipid membrane compositions. Lipid flippases catalyse phospholipid translocation from exoplasmic to the cytoplasmic leaflet of membranes. The present study aimed to analyse the effect of sex, obesity, and their interactions on the gene expression of two lipid flippases-ATP8A1 and ATP8B1-and their possible microRNA (miR) modulators in visceral adipose tissue (VAT). In total, 12 normal-weight subjects (5 premenopausal women and 7 men) and 13 morbidly obese patients (7 premenopausal women and 6 men) were submitted to surgery, and VAT samples were obtained. Gene expression levels of ATP8A1, ATP8B1, miR-548b-5p, and miR-4643 were measured in VAT. Our results showed a marked influence of obesity on VAT ATP8A1 and ATP8B1, although the effects of obesity were stronger in men for ATP8A1. Both genes positively correlated with obesity and metabolic markers. Furthermore, ATP8B1 was positively associated with miR-548b-5p and negatively associated with miR-4643. Both miRs were also affected by sex. Thus, lipid flippases are altered by obesity in VAT in a sex-specific manner. Our study provides a better understanding of the sex-specific molecular mechanisms underlying obesity, which may contribute to the development of sex-based precision medicine.

Choroidal thickness and granulocyte colony-stimulating factor in tears improve the prediction model for coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) detection in asymptomatic patients still remains controversial. The aim of our study was to evaluate the usefulness of ophthalmologic findings as predictors of the presence of CAD when added to cardiovascular classic risk factors (CRF) in patients with acute coronary cardiopathy suspicion. METHODS: After clinical stabilization, 96 patients with acute coronary cardiopathy suspicion were selected and divided in two groups: 69 patients with coronary lesions and 27 patients without coronary lesions. Their 192 eyes were subjected to a complete routine ophthalmologic examination. Samples of tear fluid were also collected to be used in the detection of cytokines and inflammatory mediators. Logistic regression models, receiver operating characteristic curves and their area under the curve (AUC) were analysed. RESULTS: Suggestive predictors were choroidal thickness (CT) (OR: 1.02, 95% CI 1.01-1.03) and tear granulocyte colony-stimulating factor (G-CSF) (OR: 0.97, 95% CI 0.95-0.99). We obtained an AUC of 0.9646 (95% CI 0.928-0.999) when CT and tear G-CSF were added as independent variables to the logistic regression model with cardiovascular CRF: sex, age, diabetes, high blood pressure, hypercholesterolemia, smoking habit and obesity. This AUC was significantly higher (p = 0.003) than the prediction derived from the same logistic regression model without CT and tear G-CSF (AUC = 0.828, 95% CI 0.729-0.927). CONCLUSIONS: CT and tear G-CSF improved the predictive model for CAD when added to cardiovascular CRF in our sample of symptomatic patients. Subsequent studies are needed for validation of these findings in asymptomatic patients.

Mitochondrial Homeostasis in Obesity-related Hypertriglyceridemia.

CONTEXT: The prevalence of obesity and hypertriglyceridemia is an alarming worldwide health issue. Mitochondria play a central role in these disorders as they control cell metabolism. OBJECTIVE: The aim of the present study was to characterize mitochondrial homeostasis in subcutaneous and visceral adipose tissue (SAT and VAT) in grade III obese patients with and without hypertriglyceridemia. Moreover, this study presents the evaluation of mitochondrial fitness as a marker for hypertriglyceridemia improvement. PATIENTS: Eight control and 12 hypertriglyceridemic (HTG) grade III obese subjects undergoing bariatric surgery were included. MAIN OUTCOME MEASURES: Anthropometric and biochemical data were obtained before and 3 months after surgery. Mitochondrial homeostasis was evaluated by mitochondrial DNA (mtDNA), gene expression and protein abundance in SAT and VAT. RESULTS: Mitophagy-related gene expression was increased in HTG SAT and VAT, while mitochondrial marker gene expression and mtDNA were decreased, indicating an altered mitochondrial homeostasis in HTG. Mitophagy protein abundance was increased in VAT of those subjects that did not improve their levels of triglycerides after bariatric surgery, whereas mitochondrial protein was decreased in the same tissue. Indeed, triglyceride levels positively correlated with mitophagy-related genes and negatively with mitochondrial content markers. Moreover, mitochondria content and mitophagy markers seem to be significant predictors of hypertriglyceridemia and hypertriglyceridemia remission. CONCLUSIONS: Mitochondrial homeostasis of adipose tissue is altered in hypertriglyceridemic patients. At the protein level, mitochondria content and mitophagy are potential markers of hypertriglyceridemia remission in obese patients after bariatric surgery. These results may contribute to the implementation of a clinical approach for personalized medicine.

Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic Drugs.

Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.

Visceral Adipose Tissue Phospholipid Signature of Insulin Sensitivity and Obesity.

Alterations in visceral adipose tissue (VAT) are closely linked to cardiometabolic abnormalities. The aim of this work is to define a metabolic signature in VAT of insulin resistance (IR) dependent on, and independent of, obesity. An untargeted UPLC-Q-Exactive metabolomic approach was carried out on the VAT of obese insulin-sensitive (IS) and insulin-resistant subjects (N = 11 and N = 25, respectively) and nonobese IS and IR subjects (N = 25 and N = 10, respectively). The VAT metabolome in obesity was defined among other things by changes in the metabolism of lipids, nucleotides, carbohydrates, and amino acids, whereas when combined with high IR, it affected the metabolism of 18 carbon fatty acyl-containing phospholipid species. A multimetabolite model created by glycerophosphatidylinositol (18:0); glycerophosphatidylethanolamine (18:2); glycerophosphatidylserine (18:0); and glycerophosphatidylcholine (18:0/18:1), (18:2/18:2), and (18:2/18:3) exhibited a highly predictive performance to identify the metabotype of "insulin-sensitive obesity" among obese individuals [area under the curve (AUC) 96.7% (91.9-100)] and within the entire study population [AUC 87.6% (79.0-96.2)]. We demonstrated that IR has a unique and shared metabolic signature dependent on, and independent of, obesity. For it to be used in clinical practice, these findings need to be validated in a more accessible sample, such as blood.

MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1.

The prevalence of metabolic syndrome (MetS) and obesity is an alarming health issue worldwide. Obesity is characterized by an excessive accumulation of white adipose tissue (WAT), and it is associated with diminished brown adipose tissue (BAT) activity. Twist1 acts as a negative feedback regulator of BAT metabolism. Therefore, targeting Twist1 could become a strategy for obesity and metabolic disease. Here, we have identified miR-337-3p as an upstream regulator of Twist1. Increased miR-337-3p expression paralleled decreased expression of TWIST1 in BAT compared to WAT. Overexpression of miR-337-3p in brown pre-adipocytes provoked a reduction in Twist1 expression that was accompanied by increased expression of brown/mitochondrial markers. Luciferase assays confirmed an interaction between the miR-337 seed sequence and Twist1 3'UTR. The inverse relationship between the expression of TWIST1 and miR-337 was finally validated in adipose tissue samples from non-MetS and MetS subjects that demonstrated a dysregulation of the miR-337-Twist1 molecular axis in MetS. The present study demonstrates that adipocyte miR-337-3p suppresses Twist1 repression and enhances the browning of adipocytes.

miR-20b, miR-296, and Let-7f Expression in Human Adipose Tissue is Related to Obesity and Type 2 Diabetes.

OBJECTIVE: This study aimed to analyze the potential association of different microRNA (miRNA) molecules with both type 2 diabetes (T2D) and obesity and determine their target genes. METHODS: Quantitative PCR was used to analyze the miR-20b, miR-296, and Let-7f levels in human visceral and subcutaneous adipose tissues (ATs) in relation to obesity and T2D, miRTarBase 4.0 was used for validation of target genes, and the Protein Analysis Through Evolutionary Relationships (PANTHER) Classification System and the Database for Annotation, Visualization and Integrated Discovery (DAVID) were used to annotate the biological processes of the predicted targets. RESULTS: In AT, miR-20b, miR-296, and Let-7f levels were significantly different between normoglycemic subjects and those with T2D. In visceral adipose tissue, miRNA levels were higher in normoglycemic/obesity samples than in T2D/obesity samples. miR-20b-miR-296 and Let-7f target genes that showed significant differences in both ATs in relation to obesity and T2D were CDKN1A, CX3CL1, HIF1A, PPP2R1B, STAT3, and VEGFA. These genes are known to be principally involved in the vascular endothelial growth factor (VEGF) and WNT pathways. CONCLUSIONS: This study provides experimental evidence of the possible correlation between AT miR-20b-miR-296-Let-7f with obesity and T2D, which might involve vascular endothelial growth factor and WNT-dependent pathways that are regulated by six different genes, suggesting a novel signaling pathway that could be important for understanding the mechanisms underlying the AT dysfunction associated with obesity and T2D.

Gut Microbiota and the Polycystic Ovary Syndrome: Influence of Sex, Sex Hormones, and Obesity.

Context: Gut microbiota play a major role in health and disease by influencing physiology, metabolism, nutrition, and immune function. Objective: To evaluate the composition of gut microbiota in women with polycystic ovary syndrome (PCOS), focusing on the influence of sex, sex hormones and obesity on the associations found. Design: Cross-sectional study. Setting: Academic hospital. Participants: We recruited 15 women with PCOS, 16 nonhyperandrogenic control women, and 15 control men. Participants were classified as nonobese (<30 kg/m2) or obese (≥30 kg/m2) according to their body mass index. Interventions: Standardization of diet for 3 consecutive days (at least 300 g of carbohydrates per day) followed by fecal sampling and a standard 75-g oral glucose tolerance test. Main Outcome Measures: Analysis of bacterial abundance and composition of gut microbiota by massive sequencing of 16S ribosomal DNA amplicons in a MiSeq platform (Illumina). Results: α Bacterial diversity was reduced in women compared with men, and ß diversity was reduced particularly in obese patients with PCOS. Women with PCOS presented with specific abnormalities in gut microbiota consisting of an increased abundance of the Catenibacterium and Kandleria genera. When all participants as a whole were considered, indexes of bacterial diversity and the abundance of several bacterial genera correlated positively with serum androgen concentrations and negatively with estradiol levels. Conclusions: The diversity and composition of the gut microbiota of young adults are influenced by the combined effects of sex, sex hormone concentrations, and obesity, presenting with specific abnormalities in women with PCOS.

MicroRNAs as regulators of mitochondrial dysfunction and obesity.

Obesity, which has become a major global epidemic, is associated with numerous comorbidities and nearly every chronic condition. Mitochondria play a central role in this disorder, as they control cell metabolism, regulating important processes, such as ATP production, lipid ß-oxidation, oxidative stress, and inflammation. MicroRNAs (miRs) have been shown to regulate many biological processes associated with obesity, comprising adipocyte differentiation, insulin action, and fat metabolism. In addition, recent studies have confirmed that miRs are important regulators of mitochondrial function by either directly modulating mitochondrial proteins or targeting mitochondrial regulators, thereby modulating metabolic process in the context of obesity. In this review, we describe the different roles of mitochondria in obesity, specifically in adipose tissue, and those miRs that are involved in mitochondrial dysfunction in this disease.