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

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

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

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.Funding for open access charge: Universidad de Málaga/CBUA

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

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

Commonalities in the Association between PPARG and Vitamin D Related with Obesity and Carcinogenesis

The PPAR nuclear receptor family has acquired great relevance in the last decade, which is formed by three different isoforms (PPARα, PPARβ/δ, and PPAR ϒ). Those nuclear receptors are members of the steroid receptor superfamily which take part in essential metabolic and life-sustaining actions. Specifically, PPARG has been implicated in the regulation of processes concerning metabolism, inflammation, atherosclerosis, cell differentiation, and proliferation. Thus, a considerable amount of literature has emerged in the last ten years linking PPARG signalling with metabolic conditions such as obesity and diabetes, cardiovascular disease, and, more recently, cancer. This review paper, at crossroads of basic sciences, preclinical, and clinical data, intends to analyse the last research concerning PPARG signalling in obesity and cancer. Afterwards, possible links between four interrelated actors will be established: PPARG, the vitamin D/VDR system, obesity, and cancer, opening up the door to further investigation and new hypothesis in this fascinating area of research

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