Reviews in Endocrine & Metabolic Disorders最新文献

Daily rhythms of metabolic function are supported by molecular circadian clock systems that are strongly regulated by feeding and fasting. Intermittent fasting diets have been associated with weight loss and improved metabolism. However, the effects of time-restricted eating (TRE) on glycemic parameters are still under debate. In this review, we aim to systematically analyze the effects of TRE on glycemic parameters. We searched on PubMed, EMBASE, and the Cochrane Library for controlled studies in which subjects followed TRE for at least 4 weeks. 20 studies were included in the qualitative systematic review, and 18 studies (n = 1169 subjects) were included in the meta-analysis. Overall, TRE had no significant effect on fasting glucose (Hedges's g = -0.08; 95% CI:-0.31,0.16; p = 0.52), but it did reduce HbA1c levels (Hedges's g = -0.27; 95% CI: -0.47, -0.06; p = 0.01). TRE significantly reduced fasting insulin (Hedges's g = -0.40; 95% CI: -0.73,-0.08; p = 0.01) and showed a tendency to decrease HOMA-IR (Hedges's g = -0.32; 95% CI:-0.66,0.02; p = 0.06). Interestingly, a cumulative analysis showed that the beneficial effects of TRE regarding glucose levels were less apparent as studies with later TRE windows (lTRE) were being included. Indeed, a subgroup analysis of the early TRE (eTRE) studies revealed that fasting glucose was significantly reduced by eTRE (Hedges's g = -0.38; 95% CI:-0.62, -0.14; p < 0.01). Our meta-analysis suggests that TRE can reduce HbA1c and insulin levels, and that timing of food intake is a crucial factor in the metabolic benefit of TRE, as only eTRE is capable of reducing fasting glucose levels in subjects with overweight or obesity.PROSPERO registration number CRD42023405946.

Gastrointestinal nutrient sensing via taste receptors may contribute to weight loss, metabolic improvements, and a reduced preference for sweet and fatty foods following bariatric surgery. This review aimed to investigate the effect of bariatric surgery on the expression of oral and post-oral gastrointestinal taste receptors and associations between taste receptor alterations and clinical outcomes of bariatric surgery. A systematic review was conducted to capture data from both human and animal studies on changes in the expression of taste receptors in oral or post-oral gastrointestinal tissue following any type of bariatric surgery. Databases searched included Medline, Embase, Emcare, APA PsychInfo, Cochrane Library, and CINAHL. Two human and 21 animal studies were included. Bariatric surgery alters the quantity of many sweet, umami, and fatty acid taste receptors in the gastrointestinal tract. Changes to the expression of sweet and amino acid receptors occur most often in intestinal segments surgically repositioned more proximally, such as the alimentary limb after gastric bypass. Conversely, changes to fatty acid receptors were observed more frequently in the colon than in the small intestine. Significant heterogeneity in the methodology of included studies limited conclusions regarding the direction of change in taste receptor expression induced by bariatric surgeries. Few studies have investigated associations between taste receptor expression and clinical outcomes of bariatric surgery. As such, future studies should look to investigate the relationship between bariatric surgery-induced changes to gut taste receptor expression and function and the impact of surgery on taste preferences, food palatability, and eating behaviour.Registration code in PROSPERO: CRD42022313992.

Osteoarthritis (OA) is an incapacitating and one of the most common physically degenerative conditions with an assorted etiology and a highly complicated molecular mechanism that to date lacks an efficient treatment. The capacity to design biological networks and accurately modify existing genomic sites holds an apt potential for applications across medical and biotechnological sciences. One of these highly specific genomes editing technologies is the CRISPR/Cas9 mechanism, referred to as the clustered regularly interspaced short palindromic repeats, which is a defense mechanism constituted by CRISPR associated protein 9 (Cas9) directed by small non-coding RNAs (sncRNA) that bind to target DNA through Watson-Crick base pairing rules where subsequent repair of the target DNA is initiated. Up-to-date research has established the effectiveness of the CRISPR/Cas9 mechanism in targeting the genetic and epigenetic alterations in OA by suppressing or deleting gene expressions and eventually distributing distinctive anti-arthritic properties in both in vitro and in vivo osteoarthritic models. This review aims to epitomize the role of this high-throughput and multiplexed gene editing method as an analogous therapeutic strategy that could greatly facilitate the clinical development of OA-related treatments since it's reportedly an easy, minimally invasive technique, and a comparatively less painful method for osteoarthritic patients.

Adipose tissue, including white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, is vital in modulating whole-body energy metabolism. While WAT primarily stores energy, BAT dissipates energy as heat for thermoregulation. Beige adipose tissue is a hybrid form of adipose tissue that shares characteristics with WAT and BAT. Dysregulation of adipose tissue metabolism is linked to various disorders, including obesity, type 2 diabetes, cardiovascular diseases, cancer, and infertility. Both brown and beige adipocytes secrete multiple molecules, such as batokines, packaged in extracellular vesicles or as soluble signaling molecules that play autocrine, paracrine, and endocrine roles. A greater understanding of the adipocyte secretome is essential for identifying novel molecular targets in treating metabolic disorders. Additionally, microRNAs show crucial roles in regulating adipose tissue differentiation and function, highlighting their potential as biomarkers for metabolic disorders. The browning of WAT has emerged as a promising therapeutic approach in treating obesity and associated metabolic disorders. Many browning agents have been identified, and nanotechnology-based drug delivery systems have been developed to enhance their efficacy. This review scrutinizes the characteristics of and differences between white, brown, and beige adipose tissues, the molecular mechanisms involved in the development of the adipocytes, the significant roles of batokines, and regulatory microRNAs active in different adipose tissues. Finally, the potential of WAT browning in treating obesity and atherosclerosis, the relationship of BAT with cancer and fertility disorders, and the crosstalk between adipose tissue with circadian system and circadian disorders are also investigated.

Endometriosis and polycystic ovary syndrome (PCOS) are two common female reproductive disorders with a significant impact on the health and quality of life of women affected. A novel hypothesis by evolutionary biologists suggested that these two diseases are inversely related to one another, representing a pair of diametrical diseases in terms of opposite alterations in reproductive physiological processes but also contrasting phenotypic traits. However, to fully explain the phenotypic features observed in women with these conditions, we need to establish a potential nexus system between the reproductive system and general biological functions. The recent discovery of kisspeptin as pivotal mediator of internal and external inputs on the hypothalamic-pituitary-gonadal axis has led to a new understanding of the neuroendocrine upstream regulation of the human reproductive system. In this review, we summarize the current knowledge on the physiological roles of kisspeptin in human reproduction, as well as its involvement in complex biological functions such as metabolism, inflammation and pain sensitivity. Importantly, these functions are known to be dysregulated in both PCOS and endometriosis. Within the evolving scientific field of "kisspeptinology", we critically discuss the clinical relevance of these discoveries and their potential translational applications in endometriosis and PCOS. By exploring the possibilities of manipulating this complex signaling system, we aim to pave the way for novel targeted therapies in these reproductive diseases.

As the incidence of neuroendocrine tumors has been rising, gender differences in epidemiology and clinical behavior have emerged, and interest into a gender-driven management of these tumors has grown with the aim to improve survival and quality of life of these patients. Somatostatin Analogues represent the first line of systemic treatment of both functional and non-functional neuroendocrine tumors, through the expression of somatostatin receptors (SSTRs) in the tumor cells, and proved effective in controlling hormonal hypersecretion and inhibiting tumor growth, improving progression-free survival and overall survival of these patients. Aim of the present review is to investigate any differences by gender in efficacy and safety of SSTS-targeted therapies, that represent the mainstay treatment of neuroendocrine tumors, as they emerge from studies of varying design and intent. Although preclinical studies have provided evidence in favor of differences by gender in tumor expression of SSTR, as well as of the role of sex hormones and related receptors in modulating SSTRs expression and function, the clinical studies conducted so far have not shown substantial differences between males and females in either efficacy or toxicity of SSTR-targeted therapies, even if with sometimes inconsistent results. Moreover, in most studies gender was not a predictor of response to treatment. Studies specifically designed to address this issue are needed to develop gender-specific therapeutic algorithms, improving patients' prognosis and quality of life.

Several epidemiological, clinical and experimental studies in recent decades have shown the relationship between exposure to stressors during development and health outcomes later in life. The characterization of these susceptible phases, such as preconception, gestation, lactation and adolescence, and the understanding of factors that influence the risk of an adult individual for developing obesity, metabolic and cardiovascular diseases, is the focus of the DOHaD (Developmental Origins of Health and Disease) research line. In this sense, advancements in molecular biology techniques have contributed significantly to the understanding of the mechanisms underlying the observed phenotypes, their morphological and physiological alterations, having as a main driving factor the epigenetic modifications and their consequent modulation of gene expression. The present narrative review aimed to characterize the different susceptible phases of development and associated epigenetic modifications, and their implication in the development of non-communicable diseases. Additionally, we provide useful insights into interventions during development to counteract or prevent long-term programming for disease susceptibility.

Undernutrition is still a recurring nutritional problem in low and middle-income countries. It is directly associated with the social and economic sphere, but it can also negatively impact the health of the population. In this sense, it is believed that undernourished individuals may be more susceptible to the development of non-communicable diseases, such as diabetes mellitus, throughout life. This hypothesis was postulated and confirmed until today by several studies that demonstrate that experimental models submitted to protein undernutrition present alterations in glycemic homeostasis linked, in part, to the reduction of insulin secretion. Therefore, understanding the changes that lead to a reduction in the secretion of this hormone is essential to prevent the development of diabetes in undernourished individuals. This narrative review aims to describe the main molecular changes already characterized in pancreatic β cells that will contribute to the reduction of insulin secretion in protein undernutrition. So, it will provide new perspectives and targets for postulation and action of therapeutic strategies to improve glycemic homeostasis during this nutritional deficiency.

The current approach for patients with differentiated thyroid carcinoma should be individualized according to the risk of recurrence, and this stratification could be used to identify the risk of persistent/recurrent disease in three scenarios: preoperatively, immediately postoperatively, and during long-term follow-up. The initial risk of recurrence will tailor the management of the patient in the preoperative and immediate postoperative settings, while the dynamic risk, which considers the responses to treatment, could guide the decision-making process for remnant ablation and long-term management.This review provides a summary of the existing information regarding the dynamic risk of recurrence and recommended management for patients with differentiated thyroid cancer. The application of this approach is essential to avoid unnecessary treatments for most patients who will have a favorable prognosis. On the other hand, it allows specific therapeutic interventions for those patients at high risk of recurrence. In the future, analysis of tumor biology and prospective studies will surely improve the accuracy of recurrence risk prediction.

Radioiodine (RAI) refractory differentiated thyroid cancer is an uncommon and challenging situation that requires a multidisciplinary approach to therapeutic strategies. The definition of RAI-refractoriness is usually a clear situation in specialized centers. However, the right moment for initiation of multikinase inhibitors (MKI), the time and availability for genomic testing, and the possibility of prescribing MKI and selective kinase inhibitors differ worldwide.Latin America (LA) refers to the territories of the world that stretch across two regions: North America (including Central America and the Caribbean) and South America, containing 8.5% of the world's population. In this manuscript, we critically review the current standard approach recommended for patients with RAI refractory differentiated thyroid cancer, emphasizing the challenges faced in LA. To achieve this objective, the Latin American Thyroid Society (LATS) convened a panel of experts from Brazil, Argentina, Chile, and Colombia. Access to MKI compounds continues to be a challenge in all LA countries. This is true not only for MKI but also for the new selective tyrosine kinase inhibitor, which will also require genomic testing, that is not widely available. Thus, as precision medicine advances, significant disparities will be made more evident, and despite efforts to improve coverage and reimbursement, molecular-based precision medicine remains inaccessible to most of the LA population. Efforts should be undertaken to alleviate the discrepancies between the current state-of-the-art care for RAI-refractory differentiated thyroid cancer and the present situation in Latin America.