Explore the vast range of titles available.

Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in regulating systemic energy homeostasis. Adipose tissue expands by a combination of an increase in adipocyte size (hypertrophy) and number (hyperplasia). The recruitment and differentiation of adipose precursor cells in the subcutaneous adipose tissue (SAT), rather than merely inflating the cells, would be protective from the obesity-associated metabolic complications. In metabolically unhealthy obesity, the storage capacity of SAT, the largest WAT depot, is limited, and further caloric overload leads to the fat accumulation in ectopic tissues (e.g., liver, skeletal muscle, and heart) and in the visceral adipose depots, an event commonly defined as “lipotoxicity.” Excessive ectopic lipid accumulation leads to local inflammation and insulin resistance (IR). Indeed, overnutrition triggers uncontrolled inflammatory responses in WAT, leading to chronic low-grade inflammation, therefore fostering the progression of IR. This review summarizes the current knowledge on WAT dysfunction in obesity and its associated metabolic abnormalities, such as IR. A better understanding of the mechanisms regulating adipose tissue expansion in obesity is required for the development of future therapeutic approaches in obesity-associated metabolic complications.

Bisphenol A (BPA) is an organic synthetic compound serving as a monomer to produce polycarbonate plastic, widely used in the packaging for food and drinks, medical devices, thermal paper, and dental materials. BPA can contaminate food, beverage, air, and soil. It accumulates in several human tissues and organs and is potentially harmful to human health through different molecular mechanisms. Due to its hormone-like properties, BPA may bind to estrogen receptors, thereby affecting both body weight and tumorigenesis. BPA may also affect metabolism and cancer progression, by interacting with GPR30, and may impair male reproductive function, by binding to androgen receptors. Several transcription factors, including PPARγ, C/EBP, Nrf2, HOX, and HAND2, are involved in BPA action on fat and liver homeostasis, the cardiovascular system, and cancer. Finally, epigenetic changes, such as DNA methylation, histones modification, and changes in microRNAs expression contribute to BPA pathological effects. This review aims to provide an extensive and comprehensive analysis of the most recent evidence about the potential mechanisms by which BPA affects human health.

Environmental endocrine disruptors (EDCs), including bisphenol-A (BPA), have been recently involved in obesity and diabetes by dysregulating adipose tissue function. Our aim was to examine whether prolonged exposure to low doses of BPA could affect adipogenesis and adipocyte metabolic functions. Therefore, 3T3-L1 pre-adipocytes were cultured for three weeks with BPA 1 nM to mimic human environmental exposure. We evaluated BPA effect on cell proliferation, differentiation, gene expression and adipocyte metabolic function. BPA significantly increased pre-adipocyte proliferation (p<0.01). In 3T3-L1 adipocytes differentiated in the presence of BPA, the expression of Peroxisome proliferator-activated receptor gamma (PPARγ), Fatty Acid Binding Protein 4/Adipocyte Protein 2 (FABP4/AP2) and CCAAT/enhancer binding protein (C/EBPα) was increased by 3.5, 1.5 and 3 folds, respectively. Mature adipocytes also showed a significant increase in lipid accumulation (p<0.05) and alterations of insulin action, with significant reduction in insulin-stimulated glucose utilization (p<0.001). Moreover, in mature adipocytes, mRNA levels of Leptin, interleukin-6 (IL6) and interferon-γ (IFNγ) were significantly increased (p<0.05). In conclusion, BPA prolonged exposure at low doses, consistent with those found in the environment, may affect adipocyte differentiation program, enhancing pre-adipocyte proliferation and anticipating the expression of the master genes involved in lipid/glucose metabolism. The resulting adipocytes are hypertrophic, with impaired insulin signaling, reduced glucose utilization and increased pro-inflammatory cytokine expression. Thus, these data supported the hypothesis that BPA exposure, during critical stages of adipose tissue development, may cause adipocyte metabolic dysfunction and inflammation, thereby increasing the risk of developing obesity-related diseases.

In Europe, multiple waves of infections with SARS-CoV-2 (COVID-19) have been observed. Here, we have investigated whether common patterns of cytokines could be detected in individuals with mild and severe forms of COVID-19 in two pandemic waves, and whether machine learning approach could be useful to identify the best predictors. An increasing trend of multiple cytokines was observed in patients with mild or severe/critical symptoms of COVID-19, compared with healthy volunteers. Linear Discriminant Analysis (LDA) clearly recognized the three groups based on cytokine patterns. Classification and Regression Tree (CART) further indicated that IL-6 discriminated controls and COVID-19 patients, whilst IL-8 defined disease severity. During the second wave of pandemics, a less intense cytokine storm was observed, as compared with the first. IL-6 was the most robust predictor of infection and discriminated moderate COVID-19 patients from healthy controls, regardless of epidemic peak curve. Thus, serum cytokine patterns provide biomarkers useful for COVID-19 diagnosis and prognosis. Further definition of individual cytokines may allow to envision novel therapeutic options and pave the way to set up innovative diagnostic tools.

The highly reactive dicarbonyl methylglyoxal (MGO) is mainly formed as byproduct of glycolysis. Therefore, high blood glucose levels determine increased MGO accumulation. Nonetheless, MGO levels are also increased as consequence of the ineffective action of its main detoxification pathway, the glyoxalase system, of which glyoxalase 1 (Glo1) is the rate-limiting enzyme. Indeed, a physiological decrease of Glo1 transcription and activity occurs not only in chronic hyperglycaemia but also with ageing, during which MGO accumulation occurs. MGO and its advanced glycated end products (AGEs) are associated with age-related diseases including diabetes, vascular dysfunction and neurodegeneration. Endothelial dysfunction is the first step in the initiation, progression and clinical outcome of vascular complications, such as retinopathy, nephropathy, impaired wound healing and macroangiopathy. Because of these considerations, studies have been centered on understanding the molecular basis of endothelial dysfunction in diabetes, unveiling a central role of MGO-Glo1 imbalance in the onset of vascular complications. This review focuses on the current understanding of MGO accumulation and Glo1 activity in diabetes, and their contribution on the impairment of endothelial function leading to diabetes-associated vascular damage.

The advances in medicine, together with lifestyle modifications, led to a rising life expectancy. Unfortunately, however, aging is accompanied by an alarming boost of age-associated chronic pathologies, including neurodegenerative and metabolic diseases. Interestingly, a non-negligible interplay between alterations of glucose homeostasis and brain dysfunction has clearly emerged. In particular, epidemiological studies have pointed out a possible association between Type 2 Diabetes (T2D) and Parkinson's Disease (PD). Insulin resistance, one of the major hallmark for etiology of T2D, has a detrimental influence on PD, negatively affecting PD phenotype, accelerating its progression and worsening cognitive impairment. This review aims to provide an exhaustive analysis of the most recent evidences supporting the key role of insulin resistance in PD pathogenesis. It will focus on the relevance of insulin in the brain, working as pro-survival neurotrophic factor and as a master regulator of neuronal mitochondrial function and oxidative stress. Insulin action as a modulator of dopamine signaling and of alpha-synuclein degradation will be described in details, too. The intriguing idea that shared deregulated pathogenic pathways represent a link between PD and insulin resistance has clinical and therapeutic implications. Thus, ongoing studies about the promising healing potential of common antidiabetic drugs such as metformin, exenatide, DPP IV inhibitors, thiazolidinediones and bromocriptine, will be summarized and the rationale for their use to decelerate neurodegeneration will be critically assessed.

Background Chronodisruption, marked by circadian rhythm misalignment, is linked to inflammatory diseases like obesity. Chronotypes, reflecting individual circadian behavior, include morning, intermediate, and evening types, with evening chronotypes showing worse body composition and higher metabolic risk. This study evaluated the inflammatory profile of visceral adipose tissue (VAT) across chronotypes in individuals with obesity and examined clock gene expression. Methods Twenty-five participants with obesity (11/14 F/M, BMI 41.59 ± 7.69 kg/m², age 41.13 ± 11.08 years) candidates for bariatric surgery were classified using the Morningness-Eveningness Questionnaire (MEQ): morning (36%), intermediate (28%), or evening (36%) chronotypes. VAT biopsies were analyzed for cytokines, chemokines, and growth factors via multiplex ELISA, and clock genes (PER1, CLOCK, BMAL1) were assessed using qPCR. Results Body composition and biochemical parameters were similar across groups, but evening chronotypes had higher triglyceride levels ( p  = 0.012) and lower phase angle ( p  = 0.035). VAT inflammatory markers, including IL-1β ( p  = 0.04), IL-8 ( p  = 0.03), bFGF ( p  = 0.01), MCP-1 ( p  = 0.01), and MIP-1β ( p  = 0.05), were highest in evening and lowest in morning chronotypes. Evening chronotypes had significantly elevated bFGF levels compared to other groups ( p  = 0.04). PER1 mRNA expression was also higher in evening chronotypes ( p  = 0.02) and correlated with VAT-released bFGF ( p  = 0.03) and IL-1β ( p  = 0.03). MEQ scores negatively correlated with VAT bFGF ( p  = 0.02), MCP-1 ( p  = 0.02), and PER1 expressions. Conclusion Despite similar metabolic profiles, evening chronotypes exhibit heightened VAT inflammation and altered clock gene expression, potentially worsening their metabolic risk.

Clear cell Carcinoma (ccRCC) is the most common and lethal subtype among renal cancers. In the present study we investigated the potential role of fatty acid-binding protein 4 (FABP4), also known as adipocyte FABP (A-FABP) or aP2 on ccRCC progression. Firstly, we found that FABP4 median serum levels were significantly higher in ccRCC patients compared to HD. Based on this result and to evaluate whether FABP4 plays a role on renal cancer malignant phenotype, we analyzed proliferation and migration in 786-O and ACHN cell lines using recombinant FABP4. We found that FABP4 significantly increased cell migration, whereas it had no significant effect on proliferation. As FABP4 is mainly expressed by adipocytes, we measured FABP4 adipocyte conditioned media (Ad-CM) levels showing that Ad-CM from ccRCC (Ad-CM ccRCC) had significantly higher mean values compared to Ad-CM obtained from Healthy Donors (HD). To assess the effects of adipocyte-released FABP-4, on cancer malignant phenotype we evaluated 786-O and ACHN proliferation and migration, using Ad-CM from ccRCC and Ad-CM from HD alone or in combination with FABP4 inhibitor BMS309403. Our results showed that Ad-CM enhanced cell proliferation in ACHN, but not in 786-O and on cell motility in both cell lines and this effect was partially reverted by BMS309403 in both cell lines. Moreover, in both cell lines, FABP4 effect was associated with an increased ERK phosphorylation. Collectively these data support the role of FABP4 in ccRCC progression and its potential use as noninvasive biomarker and therapeutic target for ccRCC.

Background The current increase of obesity and metabolic syndrome (MS) focuses attention on bisphenol-A (BPA), “obesogen” endocrine disruptor, main plastic component. Aim was to verify the role of BPA in metabolic alterations, insulin resistance, low grade inflammation and visceral obesity. Methods A cross-sectional study was performed in 76 out of 139 environmentally exposed adult males, unselected Caucasian subjects, enrolled by routine health survey at the “Federico II” University of Naples outpatient facilities. BPA plasma levels (ELISA), metabolic risk factors, homeostasis model assessment of insulin resistance index, plasma monocyte chemoattractant protein 1, interleukin-6 (IL-6) and tumor necrosis factor-alpha were performed. Clinical and biochemical parameters have been compared with BPA and pro-inflammatory cytokines levels. Results In total 24 subjects out of 76 (32%) presented with waist circumference (WC) >102 cm, 36 (47%) had impaired fasting glucose and 24 (32%) subjects had insulin resistance [11 out 52 (21%) with WC ≤102 cm and 13 out of 24 with WC >102 cm (54%), χ 2 6.825, p  = 0.009]. BPA and pro-inflammatory cytokine levels were significantly higher in subjects with visceral adiposity (WC > 102 cm). BPA correlated with WC, triglycerides, glucose homeostasis and inflammatory markers. At the multivariate analysis WC and IL-6 remained the main predictors of BPA. Conclusions Detectable BPA plasma levels have been found also in our population. The strictly association between BPA and WC, components of MS, and inflammatory markers, further supports the BPA role in visceral obesity-related low grade chronic inflammation.

Cancer survivors display impaired quality of life and increased risk to develop cardiometabolic comorbidities. Low-grade chronic inflammation (LGCI) plays a crucial role in cancer progression and in cardiometabolic diseases. Although the Mediterranean Diet is widely recognized for its beneficial effects on body composition and systemic inflammation, direct evidence of its impact on cancer survivors remains limited. This study aimed to explore the associations between inflammatory biomarkers, metabolic status, and Mediterranean diet adherence, evaluating the effectiveness of a personalized dietary intervention. A total of 132 patients with cancer remission were enrolled; anamnestic, anthropometric, bioimpedential, clinical, and nutritional data were collected. Serum concentrations of cytokines, chemokines, growth factors, and metabolic markers were measured at baseline and at a six-month follow-up. Baseline analysis revealed distinct clusters linking inflammatory status, clinical variables, and metabolic profiles, confirming associations between systemic inflammation and body composition features, without clear separation among cancer types. After dietary intervention, a significant reduction in specific inflammatory and metabolic biomarkers was observed, with distinct effects depending on tumor type. For instance, Leptin and Insulin levels decreased, particularly in Breast cancer patients, whereas Colorectal cancer patients exhibited a reduction in pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α, even in the absence of weight loss and bioimpedential feature changes. Retrospective analysis further highlighted that nutritionally modified molecules were associated with metabolic and inflammatory risk factors at baseline. Despite the lack of a control group and the high attrition rate may represent limitations for this observational pilot study, we have provided evidence that nutritional intervention could be a promising complementary strategy in oncological management by modulating key inflammatory and metabolic pathways involved in tumor pathophysiology and comorbidities.