Adipocyte-Derived Small Extracellular Vesicles from Patients with Alzheimer Disease Carry miRNAs Predicted to Target the CREB Signaling Pathway in Neurons.

Alzheimer disease (AD) is characterized by amyloid-ß (Aß) plaques, neurofibrillary tangles, synaptic dysfunction, and progressive dementia. Midlife obesity increases the risk of developing AD. Adipocyte-derived small extracellular vesicles (ad-sEVs) have been implicated as a mechanism in several obesity-related diseases. We hypothesized that ad-sEVs from patients with AD would contain miRNAs predicted to downregulate pathways involved in synaptic plasticity and memory formation. We isolated ad-sEVs from the serum and cerebrospinal fluid (CSF) of patients with AD and controls and compared miRNA expression profiles. We performed weighted gene co-expression network analysis (WGCNA) on differentially expressed miRNAs to identify highly interconnected clusters correlating with clinical traits. The WGCNA identified a module of differentially expressed miRNAs, in both the serum and CSF, that was inversely correlated with the Mini-Mental State Examination scores. Within this module, miRNAs that downregulate CREB signaling in neurons were highly represented. These results demonstrate that miRNAs carried by ad-sEVs in patients with AD may downregulate CREB signaling and provide a potential mechanistic link between midlife obesity and increased risk of AD.

Potential involvement of circulating extracellular vesicles and particles on exercise effects in malignancies.

Physical activity and exercise have been widely related to prevention, treatment, and control for several non-communicable diseases. In this context, there are innumerous pre-clinical and clinical evidence indicating the potential role of exercise, beyond cancer prevention and survival, improved quality of life, including on psychological components, bone health and cachexia, from cancer survivors is described as well. This mini-review raises the potential role of circulating extracellular and particles vesicles (EVPs) cargo, as exerkines, conducting several positive effects on adjacent and/or distant tissues such as tumor, immune, bone and muscle cells. We highlighted new perspectives about microRNAs into EVPs changes induced by exercise and its benefits on malignancies, since microRNAs can be implicated with intricated physiopathological processes. Potential microRNAs into EVPs were pointed out here as players spreading beneficial effects of exercise, such as miR-150-5p, miR-124, miR-486, and miRNA-320a, which have previous findings on involvement with clinical outcomes and as well as tumor microenvironment, regulating intercellular communication and tumor growth. For example, high-intensity interval aerobic exercise program seems to increase miR-150 contents in circulating EVPs obtained from women with normal weight or overweight. In accordance circulating EVPs miR-150-5p content is correlated with prognosis colorectal cancer, and ectopic expression of miR-150 may reduce cell proliferation, invasion and metastasis. Beyond the involvement of bioactive miRNAs into circulating EVPs and their pathways related to clinical and preclinical findings, this mini review intends to support further studies on EVPs cargo and exercise effects in oncology.

Parental obesity-induced changes in developmental programming.

Many studies support the link between parental obesity and the predisposition to develop adult-onset metabolic syndromes that include obesity, high blood pressure, dyslipidemia, insulin resistance, and diabetes in the offspring. As the prevalence of obesity increases in persons of childbearing age, so does metabolic syndrome in their descendants. Understanding how parental obesity alters metabolic programs in the progeny, predisposing them to adult-onset metabolic syndrome, is key to breaking this cycle. This review explores the basis for altered metabolism of offspring exposed to overnutrition by focusing on critical developmental processes influenced by parental obesity. We draw from human and animal model studies, highlighting the adaptations in metabolism that occur during normal pregnancy that become maladaptive with obesity. We describe essential phases of development impacted by parental obesity that contribute to long-term alterations in metabolism in the offspring. These encompass gamete formation, placentation, adipogenesis, pancreas development, and development of brain appetite control circuits. Parental obesity alters the developmental programming of these organs in part by inducing epigenetic changes with long-term consequences on metabolism. While exposure to parental obesity during any of these phases is sufficient to alter long-term metabolism, offspring often experience multiple exposures throughout their development. These insults accumulate to increase further the susceptibility of the offspring to the obesogenic environments of modern society.