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.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition worldwide. The increase in the prevalence of MASLD is linked to the global rise in obesity. MASLD encompasses a disease spectrum beginning with simple steatosis that may progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and hepatocarcinoma. Clinical studies highlight the bidirectional relationship between MASLD and systemic arterial hypertension (SAH), showing that MASLD patients have a higher risk of developing SAH. Likewise, hypertensive patients show an increased susceptibility to MASLD, suggesting mutual pathogenic mechanisms. Inflammation is a shared pathway between these two entities; MASLD pathogenesis encompasses hepatic lipotoxicity, inducing the release of pro-inflammatory mediators, which promote systemic inflammation, contributing to vascular remodeling, increased blood pressure, and deregulating the renin-angiotensin system (RAS), potentially contributing to SAH. On the other hand, chronic hypertension promotes hepatic inflammation through immune and neuroendocrine pathways, favoring progression from MASLD to MASH. This review, emphasizing the pro-inflammatory factors, explores the inflammatory crosstalk between MASLD and SAH. Understanding this interplay provides a comprehensive perspective on chronic inflammation that could link liver and vascular pathologies, offering potential therapeutic targets for treating both conditions.

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.

Non-nutritive sweeteners (NNSs) provide a sweet taste to foods and beverages without significantly adding calories. Still, their consumption has been linked to modifications in adult’s and children’s gut microbiota and the disruption of blood glucose control. Human milk microbiota are paramount in establishing infants’ gut microbiota, but very little is known about whether the consumption of sweeteners can alter it. To address this question, we sequenced DNA extracted colostrum samples from a group of mothers, who had different levels of NNS consumption, using the Ion Torrent Platform. Our results show that the “core” of colostrum microbiota, composed of the genera Bifidobacterium, Blautia, Cutibacteium, Staphylococcus, and Streptococcus, remains practically unchanged with the consumption of NNS during pregnancy, but specific genera display significant alterations, such as Staphylococcus and Streptococcus. A significant increase in the unclassified archaea Methanobrevibacter spp. was observed as the consumption frequency of NNS increased. The increase in the abundance of this archaea has been previously linked to obesity in Mexican children. NNS consumption during pregnancy could be related to changes in colostrum microbiota and may affect infants’ gut microbiota seeding and their future health.

The Th2 immune response, associated with allergic diseases and helminth infections, has emerged as a significant modulator of metabolic processes in adipose and liver tissues. Th2 cytokines, such as IL-4, IL-5, and IL-13, regulate energy metabolism, insulin resistance, and obesity-related issues. IL-4 and IL-13 play significant roles, while IL-5 mainly recruits eosinophils in visceral fat. IL-4 influences lipid metabolism via STAT6, promoting adipogenesis, lipolysis, and reducing leptin levels, thereby improving insulin resistance or inducing white adipose browning in the absence of leptin. IL-13 affects glucose metabolism by lowering gluconeogenesis and enhancing glucose control and increases energy expenditure in muscles during exercise via STAT3. Emerging therapies include recombinant cytokines, exosomes, and monoclonal antibodies targeting IL-4/IL-13 or IL-5, which are mostly approved for the treatment of allergic diseases. Their use in metabolic disorders is largely unexplored. Overall, Th2 cytokines are promising targets for obesity and metabolic diseases but require dedicated trials to assess benefits and risks.

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.