Patricia Corrales

Objective: Our aim is to study proteomic and transcriptomic changes in the subcutaneous white adipose tissue (sWAT) from patients living with severe obesity at early term after bariatric surgery (BS). Methods: Twenty‐two sWAT biopsies were collected at the time of surgery and 3 months afterward (11 for each point and from the same patient). Clinical data and metabolic parameters were measured. Targeted proteomic profiling and RNA sequencing were conducted. Bioinformatic analyses were performed to identify differentially expressed proteins and genes and their associated pathways. Results: Early‐term after BS leads to significant reductions in some clinical parameters. Twenty inflammatory proteins, including cytokines, chemokines and immune‐regulatory factors were increased after BS. Transcriptomic profiling revealed 277 significantly modulated genes (156 upregulated, 121 downregulated). ANGPTL8 was notably increased after BS and enrichment analyses highlighted its association with extracellular matrix remodelling, insulin signalling pathway, calcium metabolism and energy and lipid metabolism. Conclusions: BS induces early immunological and transcriptomic modulations in sWAT, suggesting a transient pro‐inflammatory state and tissue remodelling process. The ANGPTL8 upregulation could play a role in improving metabolic homeostasis at early term after BS. These findings offer new insights into adipose tissue remodelling after BS.

Obesity is one of the most challenging metabolic disorders affecting more than 800 million people around the world, according to the World Health Organization (WHO). In recent years, our knowledge and understanding of this multifactorial disease have been exponentially increasing, and many studies have been focusing on one of the main organs affected by obesity: adipose tissue (AT). It is known that AT undergoes remodeling due to the abnormal fat accumulation that accompanies obesity, characterized by increased immune cell infiltration, extracellular matrix (ECM) overproduction, and decreased adipogenesis, among others. Few studies have focused on adipocyte intercommunication, even though it is essential for AT homeostasis and function. In this context, GAP junction, adherens junction, and tight junction proteins can be found in these depots. In some cases, their function is well established, but in most cases it remains unknown. Claudins are the main proteins that form tight junctions (TJs), and, in recent years, studies have revealed a more extensive role of claudin proteins in intracellular signaling and control of a wide set of biological processes. This review aims to gather the main scientific evidence on the role of claudins in cell signaling, as well as what is known about these proteins in the field of obesity and adipose tissue physiology.

Objective: Because white adipose tissue is infiltrated by several immune cells and their signature in individuals with obesity has not been fully characterized, we wanted to study the most abundant population, which is macrophages, a subtype of myeloid cell.Methods: To address this objective, we performed transcriptomic analysis of subcutaneous adipose tissue (SAT)‐ and visceral adipose tissue (VAT)‐infiltrated CD11b⁺ myeloid cells from individuals with severe obesity.Results: Our results showed that gene expression in human white adipose tissue–infiltrated CD11b⁺ myeloid cells was depot‐dependent. The expression of lipid‐associated macrophage biomarkers was higher in SAT‐ than VAT‐infiltrated CD11b⁺ cells (TREM2, CD9, GPNMB, CD68). In contrast, VAT‐infiltrated CD11b⁺ cells overexpressed genes associated with a perivascular M2‐like adipose tissue macrophage signature (LYVE1, TIMD4, MRC1). In addition, no classical gene expression polarization (M1 and M2) was shown when VAT and SAT CD11b⁺ cells were compared. Finally, high levels of CD248, a sensor of lipids associated with insulin resistance, were found to be overexpressed in SAT‐ compared with VAT‐infiltrated CD11b⁺ myeloid cells.Conclusions: This study characterizes for the first time the macrophage biomarker signature in human VAT‐ and SAT‐infiltrated CD11b⁺ myeloid cells from individuals with severe obesity. Further studies are required to elucidate their potential role and specific function in the immunometabolism of individuals with obesity.

Social changes in higher education have led to a transformation in teaching innovation for developing a critical and creative mentality in students. To this end, video capsules have emerged as an optimal tool that allows combining the management of information and communication technologies and collaborative work. Video capsules were elaborated by groups of students for the virtualization of the laboratory practices of the subjects Environmental Microbiology and Biochemistry of the Degree in Environmental Sciences for two academic years (2022–2023 and 2023–2024), paying special attention to the principles of Universal Design of Learning. To assess the impact of this activity on the knowledge acquired by the students in the laboratory practices, the marks from these academic years were compared with the previous academic year (2021–2022) without the generation of video capsules. Moreover, an evaluation of the development and acquisition of cross-curricular competencies was carried out. The generation of video capsules by the students tended to increase the average grade obtained in the laboratory practices of both subjects. Furthermore, instrumental, interpersonal, and systemic competencies obtained by the students by performing the video capsules improved their transversal skills. The creation of video capsules during laboratory practices and the methodology used had a very positive direct influence on the academic outcomes of the subjects and facilitated the acquisition of transversal competencies for the students.

T-lymphocytes from visceral and subcutaneous white adipose tissue (vWAT and sWAT, respectively) can have opposing roles in the systemic metabolic changes associated with obesity. However, few studies have focused on this subject. Claudin-1 (CLDN1) is a protein involved canonically in Tight Junctions (TJs) and tissue paracellular permeability. We evaluated T lymphocytes gene expression in vWAT and sWAT and in the whole adipose depots in human samples. A Clariom D-based transcriptomics analysis was performed on T lymphocytes magnetically separated from vWAT and sWAT from patients with obesity (Cohort 1; N = 11). Expression of candidate genes resulting from that analysis was determined in whole WAT from individuals with and without obesity (Cohort 2; Patients with obesity: N = 13; Patients without obesity: N=14). We observed transcriptional differences between T lymphocytes from sWAT compared to vWAT. Specifically, CLDN1 expression was found to be dramatically induced in vWAT T cells relative to those isolated from sWAT in patients with obesity. CLDN1 was also induced in obesity in vWAT and its expression correlates with genes involved in inflammation, fibrosis and adipogenesis. These results suggest CLDN1 is a novel marker induced in obesity, and differentially expressed in T lymphocytes infiltrated in human vWAT as compared to sWAT. This protein may have a crucial role in the crosstalk between T lymphocytes and other adipose tissue cells and may contribute to inflammation, fibrosis and alter homeostasis and promote metabolic disease in obesity.

The prevalence of overweight and obesity continues to rise in the population worldwide. Because it is an important predisposing factor for cancer, cardiovascular diseases, diabetes mellitus, and COVID-19, obesity reduces life expectancy. Adipose tissue (AT), the main fat storage organ with endocrine capacity, plays fundamental roles in systemic metabolism and obesity-related diseases. Dysfunctional AT can induce excess or reduced body fat (lipodystrophy).Dido1is a marker gene for stemness; gene-targeting experiments compromised several functions ranging from cell division to embryonic stem cell differentiation, both in vivo and in vitro. We report that mutant mice lacking the DIDO N terminus show a lean phenotype. This consists of reduced AT and hypolipidemia, even when mice are fed a high-nutrient diet. DIDO mutation caused hypothermia due to lipoatrophy of white adipose tissue (WAT) and dermal fat thinning. Deep sequencing of the epididymal white fat (Epi WAT) transcriptome supportedDido1control of the cellular lipid metabolic process. We found that, by controlling the expression of transcription factors such as C/EBPα or PPARγ,Dido1is necessary for adipocyte differentiation, and that restoring their expression reestablished adipogenesis capacity inDido1mutants. Our model differs from other lipodystrophic mice and could constitute a new system for the development of therapeutic intervention in obesity.

The objective is to assess the circulating lipidome of children with obesity before and after lifestyle intervention and to compare the data to the circulating lipidome of adults with obesity before and after bariatric surgery. Ten pediatric (PE) and thirty adult (AD) patients with obesity were prospectively recruited at a referral single center. The PE cohort received lifestyle recommendations. The AD cohort underwent bariatric surgery. Clinical parameters and lipidome were analyzed in serum before and after six months of metabolic intervention. The abundance of phosphatidylinositols in the PE cohort and phosphatidylcholines in the AD significantly increased, while O-phosphatidylserines in the PE cohort and diacyl/triacylglycerols in the AD decreased. Fifteen lipid species were coincident in both groups after lifestyle intervention and bariatric surgery. Five species of phosphatidylinositols, sphingomyelins, and cholesteryl esters were upregulated. Eight species of diacylglycerols, glycerophosphoglycerols, glycerophosphoethanolamines, and phosphatidylcholines were downregulated. Most matching species were regulated in the same direction except for two phosphatidylinositols: PI(O-36:2) and PI(O-34:0). A specific set of lipid species regulated after bariatric surgery in adult individuals was also modulated in children undergoing lifestyle intervention, suggesting they may constitute a core circulating lipid profile signature indicative of early development of obesity and improvement after clinical interventions regardless of individual age.

Caloric restriction is a non‐pharmacological intervention known to ameliorate the metabolic defects associated with aging, including insulin resistance. The levels of miRNA expression may represent a predictive tool for aging‐related alterations. In order to investigate the role of miRNAs underlying insulin resistance in adipose tissue during the early stages of aging, 3‐ and 12‐month‐old male animals fed ad libitum, and 12‐month‐old male animals fed with a 20% caloric restricted diet were used. In this work we demonstrate that specific miRNAs may contribute to the impaired insulin‐stimulated glucose metabolism specifically in the subcutaneous white adipose tissue, through the regulation of target genes implicated in the insulin signaling cascade. Moreover, the expression of these miRNAs is modified by caloric restriction in middle‐aged animals, in accordance with the improvement of the metabolic state. Overall, our work demonstrates that alterations in posttranscriptional gene expression because of miRNAs dysregulation might represent an endogenous mechanism by which insulin response in the subcutaneous fat depot is already affected at middle age. Importantly, caloric restriction could prevent this modulation, demonstrating that certain miRNAs could constitute potential biomarkers of age‐related metabolic alterations.