RESUMO
Metabolic Dysfunction-Associated Fatty Liver Disease and Diabetes Mellitus are two prevalent metabolic disorders that often coexist and synergistically contribute to the progression of each other. Several pathophysiological pathways are involved in the association, including insulin resistance, inflammation, and lipotoxicity, providing a foundation for understanding the complex interrelationships between these conditions. The presence of MASLD has a significant impact on diabetes risk and the development of microvascular and macrovascular complications, and diabetes significantly contributes to an increased risk of liver fibrosis progression in MASLD and the development of hepatocellular carcinoma. Moreover, both pathologies have a synergistic effect on cardiovascular events and mortality. Therapeutic interventions targeting MASLD and diabetes are discussed, considering lifestyle modifications, pharmacological agents, and emerging treatment modalities. The review also addresses the challenges in managing these comorbidities, such as the need for personalized approaches and the potential impact on cardiovascular health. The insights gleaned from this analysis can inform clinicians, researchers, and policymakers in developing integrated strategies for preventing, diagnosing, and managing these metabolic disorders.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Resistência à Insulina , Fatores de RiscoRESUMO
[This corrects the article DOI: 10.3389/fpsyg.2021.712087.].
RESUMO
Parental psychological control (PC) hinders the development of autonomy, identity formation, and the attainment of self-determination and individuation of adolescents. The aim of this study was to deepen the understanding of which conditions increase the risk of the use of maternal PC by simultaneously considering the contribution of adolescent temperament, maternal separation anxiety, and adolescents' perception of interparental conflict. A correlational study involving a sample of 106 Chilean adolescent-mother dyads was done. Adolescents were, on average, 15.42 years old (SD = 1.09) and 77% male. Mothers were, on average, 45.46 years old (SD = 6.39). We administered self-report questionnaires to the adolescent measuring effortful control and frustration as temperamental dimensions, along with the perception of interparental conflict. Mothers reported on their separation anxiety. Both the adolescents and their mothers reported on the use of maternal PC. Adolescents reported higher levels of maternal PC than their mothers did. All predictors were associated with PC reports. Higher levels of maternal anxiety about adolescent distancing, inter-parental conflict, and adolescent frustration were associated with higher reported levels of PC. In contrast, higher levels of adolescent effortful control were associated with lower levels of maternal PC. Finally, when maternal separation anxiety and inter-parental conflict were high there was a higher use of maternal PC. The present findings inform on how adolescent's self-regulatory skills could reduce the risk of being exposed to maternal PC. And highlight the importance of using a systemic and interactional conceptualization when trying to understand their use.
RESUMO
Impaired neuronal proteostasis is a salient feature of many neurodegenerative diseases, highlighting alterations in the function of the endoplasmic reticulum (ER). We previously reported that targeting the transcription factor XBP1, a key mediator of the ER stress response, delays disease progression and reduces protein aggregation in various models of neurodegeneration. To identify disease modifier genes that may explain the neuroprotective effects of XBP1 deficiency, we performed gene expression profiling of brain cortex and striatum of these animals and uncovered insulin-like growth factor 2 (Igf2) as the major upregulated gene. Here, we studied the impact of IGF2 signaling on protein aggregation in models of Huntington's disease (HD) as proof of concept. Cell culture studies revealed that IGF2 treatment decreases the load of intracellular aggregates of mutant huntingtin and a polyglutamine peptide. These results were validated using induced pluripotent stem cells (iPSC)-derived medium spiny neurons from HD patients and spinocerebellar ataxia cases. The reduction in the levels of mutant huntingtin was associated with a decrease in the half-life of the intracellular protein. The decrease in the levels of abnormal protein aggregation triggered by IGF2 was independent of the activity of autophagy and the proteasome pathways, the two main routes for mutant huntingtin clearance. Conversely, IGF2 signaling enhanced the secretion of soluble mutant huntingtin species through exosomes and microvesicles involving changes in actin dynamics. Administration of IGF2 into the brain of HD mice using gene therapy led to a significant decrease in the levels of mutant huntingtin in three different animal models. Moreover, analysis of human postmortem brain tissue and blood samples from HD patients showed a reduction in IGF2 level. This study identifies IGF2 as a relevant factor deregulated in HD, operating as a disease modifier that buffers the accumulation of abnormal protein species.