Exploring the Th2 Response in Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Potential Modulator of the Renin-Angiotensin System (RAS) Pathway in Hypertension Development.

Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is alarmingly increasing alongside the cases of obesity worldwide. MASLD is an underestimated metabolic abnormality closely linked with a higher risk of developing systemic arterial hypertension (SAH). However, the underlying mechanism of association between MASLD and SAH remains unknown. Inflammation may link these two entities by regulating the renin-angiotensin system (RAS). For this reason, in this study, we evaluated the hepatic expression of a cytokine profile and critical molecules in the RAS pathway in patients with morbid obesity and MASLD, both with SAH. We found a statistically significant correlation between ACE levels and the cytokines IL-4, IL-10, and IL-13 of Th2 response. Furthermore, according to a multiple linear regression analysis, the cytokines IL-4 and IL-13 were the best predictors of ACE levels. Moreover, we observed increased hepatic IL-13 expression in patients with morbid obesity, MASLD, and SAH compared to those without SAH. These results allow us to propose, for the first time, that the Th2 response, through regulating the RAS, could play a critical role in developing SAH in individuals with MASLD and obesity.

Decreased Hepatic and Serum Levels of IL-10 Concur with Increased Lobular Inflammation in Morbidly Obese Patients.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.

Sucralose: From Sweet Success to Metabolic Controversies-Unraveling the Global Health Implications of a Pervasive Non-Caloric Artificial Sweetener.

Sucralose is a food additive initially used to mitigate glycemic peaks and calorie intake in patients with diabetes and obesity. Although sucralose has been considered safe for human consumption, the World Health Organization (WHO) issued a global alert in 2023 concerning the potential health implications of this artificial sweetener. This review aims to comprehensively explore the effects of sucralose intake on human health by understanding sucralose absorption, metabolism, and excretion. We also outline the role of the sweet taste 1 receptor 3 (T1R3) in mediating sucralose-dependent signaling pathways that regulate satiety, incretin release, and insulin response. Finally, we discuss the impact of sucralose on microbiome dysbiosis, inflammatory response origin, liver damage, and toxicity. Gaining a deeper understanding of the manifold effects of sucralose on human physiology will help promote further studies to ensure its consumption is deemed safe for a broader population, including children, adolescents, and pregnant women.

The cardiovascular polypill as baseline treatment improves lipid profile and blood pressure regardless of body mass index in patients with cardiovascular disease. The Bacus study.

BACKGROUND: Pharmacological treatment with lipid-lowering and antihypertensive drugs has been proposed as a strategy to improve excess cardiovascular (CV) risk among obese individuals. The present study aimed to assess whether the CV polypill (Sincronium®) could be an effective strategy to help improve CV risk factor control in obese/overweight individuals requiring secondary prevention. METHODS: This was an observational, retrospective study reviewing the hospital medical records of 479 patients with established CV disease who initiated treatment with the CV polypill between 2013 and 2019 at a general hospital in Mexico. Patients were grouped as normal weight, overweight or obese according to their initial body mass index (BMI). We collected blood pressure (BP), lipid profile, and vascular age at the last visit recorded during the period following treatment. RESULTS: At the end of the study, all assessed lipid parameters improved compared to baseline regardless of the initial BMI category (all p<0.001). There was an increase from baseline regarding the proportion of patients with at target low-density lipoprotein cholesterol after treatment (2.3% vs. 30.1%; p<0.001), more than 80% of patients achieved triglyceride levels <200 mg/dL (p<0.001), and more than 80% achieved target BP levels in all BMI subgroups (p<0.001). The subanalyses in the elderly population yielded similar results, with a significant overall improvement in lipid and BP control after initiating the CV polypill strategy. CONCLUSIONS: The use of the CV polypill as baseline therapy for secondary prevention seems to be a reasonable strategy that enhances CV risk factor control regardless of the patient's BMI.

Neurological Diseases Define the Cytokine Profile in CFS during SARS-CoV-2 Infection in Highly Ill Patients.

Neuroinflammation is critical in developing and progressing neurological diseases. The underlying pro-inflammatory cytokine expression combined with additional mechanisms in the neuropathology, such as oxidative stress, brain-blood barrier damage, and endothelial dysfunction, could contribute to the susceptibility to developing severe COVID-19. The physiopathology of SARS-CoV-2 and other human coronaviruses (H-CoVs) has not been completely understood; however, they have all been linked to a disproportionated response of the immune system, particularly an exacerbated cytokine production and the dysregulation of total cell counts. In this article, based on the compilation of studies reported by our working group regarding COVID-19 and neurological diseases, we propose that the inflammation observed in the central nervous system, through a CSF analysis, could be conditioned by neurological disease(s) and enhanced by COVID-19. Therefore, it is necessary to determine the cytokine profile in different neurological disorders to propose adequate treatments and avoid severe forms of the disease in these patients.

Newborns from Mothers Who Intensely Consumed Sucralose during Pregnancy Are Heavier and Exhibit Markers of Metabolic Alteration and Low-Grade Systemic Inflammation: A Cross-Sectional, Prospective Study.

Robust data in animals show that sucralose intake during gestation can predispose the offspring to weight gain, metabolic disturbances, and low-grade systemic inflammation; however, concluding information remains elusive in humans. In this cross-sectional, prospective study, we examined the birth weight, glucose and insulin cord blood levels, monocyte subsets, and inflammatory cytokine profile in 292 neonates at term from mothers with light sucralose ingestion (LSI) of less than 60 mg sucralose/week or heavy sucralose intake (HSI) of more than 36 mg sucralose/day during pregnancy. Mothers in the LSI (n = 205) or HSI (n = 87) groups showed no differences in age, pregestational body mass index, blood pressure, and glucose tolerance. Although there were no differences in glucose, infants from HSI mothers displayed significant increases in birth weight and insulin compared to newborns from LSI mothers. Newborns from HSI mothers showed a substantial increase in the percentage of inflammatory nonclassical monocytes compared to neonates from LSI mothers. Umbilical cord tissue of infants from HSI mothers exhibited higher IL-1 beta and TNF-alpha with lower IL-10 expression than that found in newborns from LSI mothers. Present results demonstrate that heavy sucralose ingestion during pregnancy affects neonates' anthropometric, metabolic, and inflammatory features.

Cord blood levels of interleukin-10 decrease in neonates with increased birth weight: novel implications of the cytokine network in early obesity.

Interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) are associated with body weight alterations in children, adolescents, and adults. However, little is known regarding the role of IL-10 and IFN-gamma in birth weight of neonates. One hundred eighty-two infants were enrolled and divided in groups of normal birth weight (< 95th percentile) or increased birth weight (> 95th percentile) for gestational age. IL-10 and IFN-gamma levels were measured in umbilical cord tissue and blood of newborns by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). The average value of birth weight in infants below and above the 95th percentile was 3.03±0.39 and 3.58±0.37 kg, respectively, and was independent of the mother's pre-gestational body mass index. The Student t test revealed that neonates with birth weights > 95th percentile show a significant 30% decrease in cord blood values of IL-10 as compared to infants with birth weights < 95th percentile (P<0.0001), with no significant changes in IFN-gamma levels (P=0.1661). Cord blood IL-10 was not of maternal origin but produced by umbilical cord tissue that showed less IL-10 expression in neonates with birth weights > 95th percentile than in infants with birth weights < 95th percentile (P=0.0252). Cord blood levels of IL-10 exhibited significant inverse correlations with birth weight (r = - 0.658, P=0.002) and INF-gamma (r = - 0.502, P=0.005).Conclusion: In conclusion, this work demonstrates for the first time that cord blood IL-10 decreases as birth weight increases in infants born at term and might help to improve early recognition of newborns at higher risk of developing obesity in childhood or adulthood. What is Known: • Reduction in interleukin-10 levels has been associated with obesity in adolescents and adults but not newborns. • The number of neonates with excess birth weight has alarmingly increased in the last 30 years. What is New: • We demonstrate that umbilical cord blood levels of interleukin-10 clearly decrease as birth weight increases. • Interleukin-10 and interferon-gamma integrate a cytokine network that might play a role in obesity in infants.

Environmental Pollution as a Risk Factor in Testicular Tumour Development: Focus on the Interaction between Bisphenol A and the Associated Immune Response.

Bisphenol A (BPA) is an endocrine disruptor to which animals and humans are highly exposed. Many reports have established a relationship between BPA exposure and breast cancer incidence, especially during critical periods of development. However, its effects on the immune response in testicular tumour growth have not yet been described. Thus, we wanted to analyse the effect of perinatal BPA exposure in pregnant female mice and the immune response modulation and tumour growth in an intratesticular cancer model in offspring male mice. Pregnant female mice were exposed to a dose of 250 mg/kg/day/body weight of BPA in their drinking water. In adulthood, male offspring underwent intrascrotal inoculation with 4T1 cancer cells. On day 21 after inoculation, mice were euthanised, and serum was obtained to measure BPA levels using HPLC coupled to mass spectrometry. The percentages of immune cell populations in peripheral lymph nodes (PLN), the spleen and tumours were evaluated by flow cytometry. In addition, the tumour expression of IL-10, TNF-α and TGF-ß was analysed by RT-PCR. Of note, we found detectable circulating levels of BPA in the offspring of mothers exposed to it while pregnant. Remarkably, BPA treatment promoted tumour growth by about 75% compared to mice coming from female mice that did not receive the compound. Perinatal exposure to BPA modulated the percentages of different immune cells in the spleen and PLN. In addition, the expression of inflammatory-related cytokines (IL-10 and TNF-α) in the tumours was significantly enhanced compared to control and vehicle groups. In conclusion, the perinatal BPA administration in pregnant female mice modulated different cellular and molecular immune components that resulted in outstanding testicular tumour size in male offspring.

Breast Cancer Metastasis: Are Cytokines Important Players During Its Development and Progression?

In breast cancer, an uncontrolled cell proliferation leads to tumor formation and development of a multifactorial disease. Metastasis is a complex process that involves tumor spread to distant parts of the body from its original site. Metastatic dissemination represents the main physiopathology of cancer. Inter- and intracellular communication in all systems in vertebrates is mediated by cytokines, which are highly inducible, secretory proteins, produced not only by immune system cells, but also by endocrine and nervous system cells. It has become clear in recent years that cytokines, as well as their receptors are produced in the organisms under physiological and pathological conditions; recently, they have been closely related to breast cancer metastasis. The exact initiation process of breast cancer metastasis is unknown, although several hypotheses have emerged. In this study, we thoroughly reviewed the role of several cytokines in breast cancer metastasis. Data reviewed suggest that cytokines and growth factors are key players in the breast cancer metastasis induction. This knowledge must be considered with the aim to development of new therapeutic approaches to counter breast cancer metastasis.