Benefits of polyphenols on gut microbiota and implications in human health

The biological properties of dietary polyphenols are greatly dependent on their bioavailability that, in turn, is largely influenced by their degree of polymerization. The gut microbiota play a key role in modulating the production, bioavailability and, thus, the biological activities of phenolic metabolites, particularly after the intake of food containing high-molecular-weight polyphenols. In addition, evidence is emerging on the activity of dietary polyphenols on the modulation of the colonic microbial population composition or activity. However, although the great range of health-promoting activities of dietary polyphenols has been widely investigated, their effect on the modulation of the gut ecology and the two-way relationship 'polyphenols ↔ microbiota' are still poorly understood. Only a few studies have examined the impact of dietary polyphenols on the human gut microbiota, and most were focused on single polyphenol molecules and selected bacterial populations. This review focuses on the reciprocal interactions between the gut microbiota and polyphenols, the mechanisms of action and the consequences of these interactions on human health

Inverse relation between FASN expression in human adipose tissue and the insulin resistance level

<p>Abstract</p> <p>Background</p> <p>Adipose tissue is a key regulator of energy balance playing an active role in lipid storage and may be a dynamic buffer to control fatty acid flux. Just like PPARγ, fatty acid synthesis enzymes such as FASN have been implicated in almost all aspects of human metabolic alterations such as obesity, insulin resistance or dyslipemia. The aim of this work is to investigate how FASN and PPARγ expression in human adipose tissue is related to carbohydrate metabolism dysfunction and obesity.</p> <p>Methods</p> <p>The study included eighty-seven patients which were classified according to their BMI and to their glycaemia levels in order to study FASN and PPARγ gene expression levels, anthropometric and biochemical variables.</p> <p>Results</p> <p>The main result of this work is the close relation between FASN expression level and the factors that lead to hyperglycemic state (increased values of glucose levels, HOMA-IR, HbA1c, BMI and triglycerides). The correlation of the enzyme with these parameters is inversely proportional. On the other hand, PPARγ is not related to carbohydrate metabolism.</p> <p>Conclusions</p> <p>We can demonstrate that FASN expression is a good candidate to study the pathophysiology of type II diabetes and obesity in humans.</p

Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance

Evidence from observational and in vitro studies suggests that insulin growth-factor-binding protein type 2 (IGFBP2) is a promising protein in non-communicable diseases, such as obesity, insulin resistance, metabolic syndrome, or type 2 diabetes. Accordingly, great efforts have been carried out to explore the role of IGFBP2 in obesity state and insulin-related diseases, which it is typically found decreased. However, the physiological pathways have not been explored yet, and the relevance of IGFBP2 as an important pathway integrator of metabolic disorders is still unknown. Here, we review and discuss the molecular structure of IGFBP2 as the first element of regulating the expression of IGFBP2. We highlight an update of the association between low serum IGFBP2 and an increased risk of obesity, type 2 diabetes, metabolic syndrome, and low insulin sensitivity. We hypothesize mechanisms of IGFBP2 on the development of obesity and insulin resistance in an insulin-independent manner, which meant that could be evaluated as a therapeutic target. Finally, we cover the most interesting lifestyle modifications that regulate IGFBP2, since lifestyle factors (diet and/or physical activity) are associated with important variations in serum IGFBP2

Effect of a Weight Loss and Lifestyle Intervention on Dietary Behavior in Men with Obstructive Sleep Apnea: The INTERAPNEA Trial

This study investigated the effects of an eight-week interdisciplinary weight loss and lifestyle intervention on dietary behavior in men who were overweight/had obesity and moderateto- severe obstructive sleep apnea (OSA). It was based on data from INTERAPNEA (ClinicalTrials.gov ID: NCT03851653); a randomized clinical trial conducted from April 2019 to April 2020. Men aged 18–65 years with moderate-to-severe OSA and a body mass index 25 kg/m2 were randomly assigned to a usual-care group or an eight-week interdisciplinary weight loss and lifestyle intervention combined with usual-care. Dietary behavior was assessed through the Food Behavior Checklist (FBC) and the Mediterranean Diet Adherence Screener (MEDAS). Of the 89 participants who underwent randomization, 75 completed the intervention endpoint assessment, 89 participants being therefore included in the intention-to-treat analyses, and 75 in the per-protocol approach. As compared with usual-care, the intervention group had greater improvements at intervention endpoint in dietary behavior, as measured by the FBC total score (20% increase in FBC total score, mean between-group difference, 8.7; 95% confidence interval, 5.7 to 11.7), and MEDAS total score (33% increase in MEDAS total score, mean between-group difference, 2.1; 95% CI 1.3 to 2.9). At 6 months after intervention, the intervention group also had greater improvements in both the FBC total score (15% increase) and MEDAS total score (25% increase), with mean between-group differences of 7.7 (CI 95%, 4.4 to 10.9) and 1.7 (CI 95%, 0.9 to 2.6), respectively. An eight-week interdisciplinary weight loss and lifestyle intervention resulted in meaningful and sustainable improvements in dietary behavior, including adherence to the Mediterranean diet in men who were overweight/ had obesity and CPAP-treated moderate-to-severe OSA.Spanish Government FPU16/01093 FPU14/04172 FPU19/01609University of Granada-LoMonaco S.L. Sleep Research Cathedra University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Regional Ministry of Economy, Knowledge, Enterprise, and Universities (CECEU) of Andalusia (European Regional Development Funds) SOMM17/6107/UG

Obesity-related glomerulopathy: Current approaches and future perspectives

Obesity-related glomerulopathy (ORG) is a silent comorbidity which is increasing inincidence as the obesity epidemic escalates. ORG is associated with serious healthconsequences including chronic kidney disease, end-stage renal disease (ESRD), andincreased mortality. Although the pathogenic mechanisms involved in the develop-ment of ORG are not fully understood, glomerular hemodynamic changes, renin-angiotensin-aldosterone system (RAAS) overactivation, insulin-resistance, inflamma-tion and ectopic lipid accumulation seem to play a major role. Despite albuminuriabeing commonly used for the non-invasive evaluation of ORG, promising biomarkersof early kidney injury that are emerging, as well as new approaches with proteomicsand metabolomics, might permit an earlier diagnosis of this disease. In addition, theassessment of ectopic kidney fat by renal imaging could be a useful tool to detectand evaluate the progression of ORG. Weight loss interventions appear to be effec-tive in ORG, although large-scale trials are needed. RAAS blockade has a ren-oprotective effect in patients with ORG, but even so, a significant proportion ofpatients with ORG will eventually progress to ESRD despite therapeutic efforts. It isnoteworthy that certain antidiabetic agents such as sodium-glucose cotransporter2 inhibitors (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) couldbe useful in the treatment of ORG through different pleiotropic effects. In this article,we review current approaches and future perspectives in the care and treatmentof ORGInstitute of Health“Carlos III”(ISCIII), Grant/Award Numbers: JR 19/00054, CM 17/00169,PI20/01559; Funding for open access charge: Universidad de Málaga / CBU

The MRC1/CD68 ratio is positively associated with adipose tissue lipogenesis and with muscle mitochondrial gene expression in humans

This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background]: Alternative macrophages (M2) express the cluster differentiation (CD) 206 (MCR1) at high levels. Decreased M2 in adipose tissue is known to be associated with obesity and inflammation-related metabolic disturbances. Here we aimed to investigate MCR1 relative to CD68 (total macrophages) gene expression in association with adipogenic and mitochondrial genes, which were measured in human visceral [VWAT, n = 147] and subcutaneous adipose tissue [SWAT, n = 76] and in rectus abdominis muscle (n = 23). The effects of surgery-induced weight loss were also longitudinally evaluated (n = ).[Results]: MCR1 and CD68 gene expression levels were similar in VWAT and SWAT. A higher proportion of CD206 relative to total CD68 was present in subjects with less body fat and lower fasting glucose concentrations. The ratio MCR1/CD68was positively associated with IRS1gene expression and with the expression of lipogenic genes such as ACACA, FASN and THRSP, even after adjusting for BMI. The ratio MCR1/CD68 in SWAT increased significantly after the surgery-induced weight loss (+44.7%; p = 0.005) in parallel to the expression of adipogenic genes. In addition, SWAT MCR1/CD68ratio was significantly associated with muscle mitochondrial gene expression (PPARGC1A, TFAM and MT-CO3). AT CD206 was confirmed by immunohistochemistry to be specific of macrophages, especially abundant in crown-like structures. [Conclusion]: A decreased ratio MCR1/CD68 is linked to adipose tissue and muscle mitochondrial dysfunction at least at the level of expression of adipogenic and mitochondrial genes. © 2013 moreno-navarrete et al.This work was supported by grant SAF-2009-10461 and grant PI11-00214 from the Ministerio de Economía y Competitividad, Spain.Peer Reviewe

Metabolomics for Biomarkers of Type 2 Diabetes Mellitus: Advances and Nutritional Intervention Trends

Abstract Metabolic characterization of type 2 diabetes mellitus (T2DM) is crucial for the identification of individuals at risk for developing diabetes and T2DM-related vascular complications as well as for monitoring disease progression. The application of metabolomics to diabetes research may lead to the identification and discovery of diagnostic and prognostic T2DM biomarkers, in addition to elucidating disease pathways. In the present review, we summarize the distinct classes of metabolites that have been proposed as potential biomarkers for progressing stages of T2DM by metabolomic approaches. Several studies have demonstrated that the metabolism of carbohydrates, lipids, and amino acids is considerably altered in prediabetes and continue to vary over the course of T2DM progression. The identification of intermediate metabolites involved in glycolysis, gluconeogenesis, the tricarboxylic acid cycle, lipolysis, and proteolysis have provided evidence of these metabolic dysfunctions. Finally, given the increasing worldwide incidence of T2DM and its related complications, research should focus on the impact of lifestyle factors, particularly diet, at the metabolomic level for better understanding and improved healthcare strategie

Metabolomic insights into the intricate gut microbial-host interaction in the development of obesity and type 2 diabetes

Gut microbiota has recently been proposed as a crucial environmental factor in the development of metabolic diseases such as obesity and type 2 diabetes, mainly due to its contribution in the modulation of several processes including host energy metabolism, gut epithelial permeability, gut peptide hormone secretion, and host inflammatory state. Since the symbiotic interaction between the gut microbiota and the host is essentially reflected in specific metabolic signatures, much expectation is placed on the application of metabolomic approaches to unveil the key mechanisms linking the gut microbiota composition and activity with disease development. The present review aims to summarize the gut microbialhost co-metabolites identified so far by targeted and untargeted metabolomic studies in humans, in association with impaired glucose homeostasis and/or obesity. An alteration of the co-metabolism of bile acids, branched fatty acids, choline, vitamins (i.e., niacin), purines, and phenolic compounds has been associated so far with the obese or diabese phenotype, in respect to healthy controls. Furthermore, anti-diabetic treatments such as metformin and sulfonylurea have been observed to modulate the gut microbiota or at least their metabolic profiles, thereby potentially affecting insulin resistance through indirect mechanisms still unknown. Despite the scarcity of the metabolomic studies currently available on the microbialhost crosstalk, the data-driven results largely confirmed findings independently obtained from in vitro and animal model studies, putting forward the mechanisms underlying the implication of a dysfunctional gut microbiota in the development of metabolic disorders

Quantifying the human diet in the crosstalk between nutrition and health by multi-targeted metabolomics of food and microbiota-derived metabolites

Background: Metabolomics is a powerful tool for investigating the association between nutrition and health status. Although urine is commonly employed for studying the metabolism and transformation of food components, the use of blood samples could be preferable to gain new insights into the bioavailability of diet-derived compounds and their involvement in health. However, the chemical complexity of blood samples hinders the analysis of this biological fluid considerably, which makes the development of novel and comprehensive analytical methods mandatory. Methods: In this work, we optimized a multi-targeted metabolomics platform for the quantitative and simultaneous analysis of 450 food-derived metabolites by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. To handle the chemical complexity of blood samples, three complementary extraction methods were assayed and compared in terms of recovery, sensitivity, precision and matrix effects with the aim of maximizing metabolomics coverage: protein precipitation, reversed solid-phase extraction, and hybrid protein precipitation with solid-phase extraction-mediated phospholipid removal. Results: After careful optimization of the extraction conditions, protein precipitation enabled the most efficient and high-throughput extraction of the food metabolome in plasma, although solid-phase extraction-based protocols provided complementary performance for the analysis of specific polyphenol classes. The developed method yielded accurate recovery rates with negligible matrix effects, and good linearity, as well as high sensitivity and precision for most of the analyzed metabolites. Conclusions: The multi-targeted metabolomics platform optimized in this work enables the simultaneous detection and quantitation of 450 dietary metabolites in short-run times using small volumes of biological sample, which facilitates its application to epidemiological studies

Dietary and Gut Microbiota Polyamines in Obesity- and Age-Related Diseases

The polyamines putrescine, spermidine, and spermine are widely distributed polycationic compounds essential for cellular functions. Intracellular polyamine pools are tightly regulated by a complex regulatory mechanism involving de novo biosynthesis, catabolism, and transport across the plasma membrane. In mammals, both the production of polyamines and their uptake from the extracellular space are controlled by a set of proteins named antizymes and antizyme inhibitors. Dysregulation of polyamine levels has been implicated in a variety of human pathologies, especially cancer. Additionally, decreases in the intracellular and circulating polyamine levels during aging have been reported. The differences in the polyamine content existing among tissues are mainly due to the endogenous polyamine metabolism. In addition, a part of the tissue polyamines has its origin in the diet or their production by the intestinal microbiome. Emerging evidence has suggested that exogenous polyamines (either orally administrated or synthetized by the gut microbiota) are able to induce longevity in mice, and that spermidine supplementation exerts cardioprotective effects in animal models. Furthermore, the administration of either spermidine or spermine has been shown to be effective for improving glucose homeostasis and insulin sensitivity and reducing adiposity and hepatic fat accumulation in diet-induced obesity mouse models. The exogenous addition of agmatine, a cationic molecule produced through arginine decarboxylation by bacteria and plants, also exerts significant effects on glucose metabolism in obese models, as well as cardioprotective effects. In this review, we will discuss some aspects of polyamine metabolism and transport, how diet can affect circulating and local polyamine levels, and how the modulation of either polyamine intake or polyamine production by gut microbiota can be used for potential therapeutic purposes