Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) and Thyroid Function in Childhood Obesity: A Vicious Circle?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a multisystem disorder characterized by the presence of fatty liver degeneration associated with excess adiposity or prediabetes/type 2 diabetes or metabolic dysregulation. An intricate relationship between the liver and thyroid has been reported in both health and disease. Simultaneously, there is a strong correlation between obesity and both MAFLD and thyroid dysfunction. In this narrative review, we highlighted the relationship between MAFLD and thyroid function in children and adolescents with obesity in order to explore how thyroid hormones (THs) act as predisposing factors in the onset, progression, and sustainability of MAFLD. THs are integral to the intricate balance of metabolic activities, ensuring energy homeostasis, and are indispensable for growth and development. Regarding liver homeostasis, THs have been suggested to interact with liver lipid homeostasis through a series of processes, including stimulating the entry of free fatty acids into the liver for esterification into triglycerides and increasing mitochondrial ß-oxidation of fatty acids to impact hepatic lipid accumulation. The literature supports a correlation between MAFLD and obesity, THs and obesity, and MAFLD and THs; however, results in the pediatric population are very limited. Even though the underlying pathogenic mechanism involved in the relationship between MAFLD and thyroid function remains not fully elucidated, the role of THs as predisposing factors of MAFLD could be postulated. A potential vicious circle among these three conditions cannot be excluded. Identifying novel elements that may contribute to MAFLD could offer a practical approach to assessing children at risk of developing the condition.

Association between Vitamin D Levels, Puberty Timing, and Age at Menarche.

Pubertal development represents the process of physical maturation where an adolescent reaches sexual maturity and attains reproductive function. The effects of vitamin D are mainly mediated by the vitamin D receptor (VDR), which is expressed in almost all body cells, including the ovary and human pituitary gland and animal hypothalamus. Thus, vitamin D has gained great interest as pathogenic factor of pubertal disorders and fertility. This narrative review aimed to provide a broad overview of the available literature regarding the association between vitamin D levels, puberty timing, and age at menarche. A review of the data on the involvement of micronutrient deficiency, as a modifiable cause of pubertal disorders, is important for the prediction and prevention of deficiencies as well as for fertility protection and should be considered a public health priority. Reported data support that vitamin D is a regulator of neuroendocrine and ovarian physiology and, more in detail, a deficiency of vitamin D is involved in altered pubertal timing. Considering the long-term consequences of early pubertal development and early menarche, the detection of modifiable causes is crucial in preventive strategies. Future studies in humans and with an increased scale are needed to elucidate the vitamin D role in sexual maturation and puberty development.

Ultra-Processed Food, Reward System and Childhood Obesity.

Obesity and overweight are a major public health problem globally. Diet quality is critical for proper child development, and an unhealthy diet is a preventable risk factor for noncommunicable diseases (NCDs), such as obesity. Consumption of sugar-sweetened beverages and ultra-processed foods (UPFs) in childhood may increase the BMI/BMI z-score, body fat percentage, or likelihood of overweight. A strict feeding regulation system allows for sufficient food to be consumed to meet ongoing metabolic demands while avoiding overconsumption. This narrative review explores the issues of obesity and the regulation of food intake related to reward systems and UPF consumption. Nutrient composition alone cannot explain the influence of UPFs on the risk of obesity. Furthermore, the non-nutritional properties of UPFs may explain the mechanisms underlying the relationship with obesity and NCDs. UPFs are designed to be highly palatable, appealing, and energy dense with a unique combination of the main taste enhancer ingredients to generate a strong rewarding stimulus and influence the circuits related to feeding facilitation. How individual UPF ingredients influence eating behavior and reward processes remains not fully elucidated. To increase the knowledge on the relationship between UPFs and pediatric obesity, it may be useful to limit the rapid growth in the prevalence of obesity and subsequent related complications, and to develop new strategies for appropriate food and nutrition policies.

Reference intervals for thyroid biomarkers to enhance the assessment of thyroid status in childhood and adolescence.

OBJECTIVES: The determination of assay-dependent upper and lower reference limits (URL, LRL) of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) during childhood and adolescence, is challenging. METHODS: Thyroid hormones were measured via the Abbott Alinity system in 502 euthyroid children partitioned in the following age groups: ≤2, 2.1-10, and 10.1-18 years. The 97.5th and 2.5th percentiles (URL and LRL) were derived according to CLSI EP28- A3c guidelines. Quantile regression models were used to assess: (a) 90% confidence intervals of the URL and LRL, (b) the effect of age on URL and LRL within each age class and on overall age range, (c) the difference between the URLs and LRLs estimated for each age partition with an estimate of the confidence interval divided by the reference interval being derived (CI/RI). RESULTS: The CI/RI for the LRLs are smaller as compared to the URLs, except for FT4 for the 2.1-10 years age group. Considering the CI/RI and the overlap between CIs across the three age groups, one single LRL might be considered for TSH, FT3 and FT4 between 0 and 18 years. However, for the URL, there was a noticeable decrease in the URL over the 3 age groups for all three biomarkers, with there being no overlap in CIs for the URL between the ≤2 vs. the 10.1-19 years age groups. CONCLUSIONS: A common LRL for TSH, FT4 and FT3 for patients aged ≤18 years may be utilized when these biomarkers are measured with the Alinity system. For the URLs the use of age-specific URLs for these biomarkers is recommended.

The Effect of Healthy Lifestyle Strategies on the Management of Insulin Resistance in Children and Adolescents with Obesity: A Narrative Review.

Childhood obesity is characterized by an increased risk of several metabolic derangements including insulin resistance (IR). The strongest recommendations to prevent obesity and related complications are a balanced and adequate diet and practicing physical activity from early childhood. In this review, we propose to present the effects of healthy lifestyle strategies, including physical exercise and dietary approaches, on the management of IR and related metabolic derangements. All types of exercise (aerobic, resistance and combined training) effectively reduce IR in pediatric patients with obesity; it seems that aerobic and combined training stimulate greater improvements in IR compared to resistance training. Balanced normocaloric or hypocaloric dietary approaches are also valid strategies to address IR; it is not possible to assess the long-term impact of varying macronutrients on cardiometabolic risk. The glycemic index/load evaluation is a useful dietary approach to glucose metabolism control. Similarly, they should adopt the principle of the Mediterranean diet. Randomized studies with longer monitoring are needed to define the benefits of nutritional supplementation on IR. Considering that healthy style acquisition could track to later ages, programs of healthy lifestyle starting with children offer a better preventive strategy to preserve metabolic control and children's health.

Benefits of Physical Exercise as Approach to Prevention and Reversion of Non-Alcoholic Fatty Liver Disease in Children and Adolescents with Obesity.

Non-alcoholic fatty liver disease (NAFLD) is an important health concern during childhood; indeed, it is the most frequent cause of chronic liver diseases in obese children. No valid pharmacological therapies for children affected by this condition are available, and the recommended treatment is lifestyle modification, usually including nutrition and exercise interventions. In this narrative review, we summarized up-to-date information on the benefits of physical exercise on NAFLD in children and adolescents with obesity. The role of exercise as non-pharmacological treatment was emphasized in order to provide recent advances on this topic for clinicians not deeply involved in the field. Several studies on obese children and adults confirm the positive role of physical activity (PA) in the treatment of NAFLD, but to date, there are no pediatric randomized clinical trials on exercise versus usual care. Among the pathogenic mechanisms involved in the PA effects on NAFLD, the main players seem to be insulin resistance and related inflammation, oxidative stress, and gut dysbiosis, but further evaluations are necessary to deeply understand whether these factors are correlated and how they synergistically act. Thus, a deeper research on this theme is needed, and it would be extremely interesting.

Bioarchaeology-related studies in the Arabian Gulf: potentialities and shortcomings.

Archaeological studies provide a powerful tool to understand the prehistoric societies, especially when combined to cutting-edge morphological and molecular anthropological analyses, allowing reconstructing past population dynamics, admixture events, and socio-cultural changes. Despite the advances achieved in the last decades by archaeological studies worldwide, several regions of the World have been spared from this scientific improvement due to various reasons. The Arabian Gulf represents a unique ground to investigate, being the passageway for human migrations and one of the hypothesized areas in which Neanderthal introgression occurred. A number of archaeological sites are currently present in the Arabian Gulf and have witnessed the antiquity and the intensiveness of the human settlements in the region. Nevertheless, the archaeological and anthropological investigation in the Gulf is still in its infancy. Data collected through archaeological studies in the area have the potential to help answering adamant questions of human history from the beginning of the structuring of genetic diversity in human species to the Neolithisation process. This review aims at providing an overview of the archaeological studies in the Arabian Gulf with special focus to Qatar, highlighting potentialities and shortcomings.

A multicomponent approach in the discovery of indoleamine 2,3-dioxygenase 1 inhibitors: Synthesis, biological investigation and docking studies.

Indoleamine 2,3-dioxygenase plays a crucial role in immune tolerance and has emerged as an attractive target for cancer immunotherapy. In this study, the Passerini and Ugi multicomponent reactions have been employed to assemble a small library of imidazothiazoles that target IDO1. While the p-bromophenyl and the imidazothiazole moieties have been kept fixed, a full SAR study has been performed on the side-chain, leading to the discovery of nine compounds with sub-micromolar IC50 values in the enzyme-based assay. Compound 7d, displaying a α-acyloxyamide substructure, is the most potent compound, with an IC50 value of 0.20 µM, but a low activity in a cell-based assay. Compound 6o, containing a α-acylaminoamide moiety, shows an IC50 value of 0.81 µM in the IDO1-based assay, a full biocompatibility at 10 µM, together with a modest inhibitory activity in A375 cells. Molecular docking studies show that both 7d and 6o display a unique binding mode in the IDO1 active site, with the side-chain protruding in an additional pocket C, where a crucial hydrogen bond is formed with Lys238. Overall, this work describes an isocyanide based-multicomponent approach as a straightforward and versatile tool to rapidly access IDO1 inhibitors, providing a new direction for their future design and development.