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 1nM 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.

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.

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.