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T cells play critical roles in adipose tissue (AT) inflammation. The role of CD20 + T cell in AT dysfunction and their contributing to insulin resistance (IR) and type 2 diabetes progression, is not known. The aim was to characterize CD20 + T cells in omental (OAT), subcutaneous (SAT) and peripheral blood (PB) from subjects with obesity (OB, n = 42), by flow cytometry. Eight subjects were evaluated before (T1) and 12 months post (T2) bariatric/metabolic surgery (BMS). PB from subjects without obesity (nOB, n = 12) was also collected. Higher percentage of CD20 + T cells was observed in OAT, compared to PB or SAT, in OB-T1. CD20 expression by PB CD4 + T cells was inversely correlated with adiposity markers, while follicular-like CD20 + T cells were positively correlated with impaired glucose tolerance (increased HbA1c). Notably, among OB-T1, IR establishment was marked by a lower percentage and absolute number of PB CD20 + T cells, compared nOB. Obesity was associated with higher percentage of activated CD20 + T cells; however, OAT-infiltrated CD20 + T cells from OB-T1 with diabetes displayed the lowest activation. CD20 + T cells infiltrating OAT from OB-T1 displayed a phenotype towards IFN-γ-producing Th1 and Tc1 cells. After BMS, the percentage of PB CD4 + CD20 + T cells increased, with reduced Th1 and increased Th17 phenotype. Whereas in OAT the percentage of CD20 + T cells with Th1/17 and Tc1/17 phenotypes increased. Interestingly, OAT from OB pre/post BMS maintained higher frequency of effector memory CD20 + T cells. In conclusion, CD20 + T cells may play a prominent role in obesity-related AT inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Substance P (SP) is an 11-amino acid peptide that belongs to the tachykinin family of peptides. SP acts in the brain and in the periphery as a neuropeptide, neurotransmitter, and hormone affecting diverse physiologic pathways, mainly via its high-affinity neurokinin-1 receptor (NK-1R). Its presence in the hypothalamus and other areas of the brain that regulate feeding as well as in the stomach and small intestine prompted us to investigate its role on appetite control and energy balance., Methods: CJ 012,255 (CJ), a SP antagonist that binds to NK-1R, was injected into lean, diet-induced obese (DIO), and genetically obese (ob/ob) mice, and its effects on body weight, adiposity, and insulin sensitivity were investigated., Results: CJ administration prevented weight gain and accumulation of fat after 2 weeks of high-fat feeding, whereas similar CJ treatment in obese mice (following 3 months of high-fat diet) resulted in weight loss, reduction in adiposity, and improvement of insulin sensitivity, in part because of inhibition of food intake. The effects of SP in the control of energy balance are, at least in part, leptin independent because CJ treatment was also effective in leptin-deficient mice. Peripheral SP administration resulted in a mild, dose-dependent increase in food intake, evident 3 hours post-SP injection., Conclusions: CJ reduces appetite and promotes weight loss in mice. We speculate that NK-1R antagonists, already tested in clinical trials for various diseases, may represent a potential target against obesity.

Despite the known link between obesity and insulin resistance (IR) to chronic low-grade inflammation, new markers capable of early IR detection are needed. Immune cells are components of adipose tissue's (AT) stromal vascular fraction (SVF) that regulate AT homeostasis. The altered phenotype and function of AT-infiltrating immune cells may contribute to the development and maintenance of local AT inflammation observed under obesity-induced IR conditions. Impaired AT-specific immunometabolic function may influence the whole organism. Therefore, AT-infiltrating immune cells may be important players in the development of obesity-related metabolic complications, such as type 2 diabetes mellitus (T2DM). B and T cells, particularly CD20+ T cells, play important roles in human pathology, such as autoimmune disease and cancer. However, the question remains as to whether CD20+ T cells have an important contribution to the development of obesity-related IR. While circulating CD20+ T cells are mostly of the central memory phenotype (i.e. antigen-experienced T cells with the ability to home to secondary lymphoid organs), tissues-infiltrated CD20+ T cells are predominantly of the effector memory phenotype (i.e. antigen-experienced T cells that preferentially infiltrate peripheral tissues). The latter produce pro-inflammatory cytokines, such as IFN-γ and IL-17, which play a role in obesity-related IR development. This review describes the CD20 molecule and its presence in both B and T cells, shedding light on its ontogeny and function, in health and disease, with emphasis on AT. The link between CD20+ T cell dysregulation, obesity, and IR development supports the role of CD20+ T cells as markers of adipose tissue dysmetabolism. [ABSTRACT FROM AUTHOR]

Low-grade inflammation is closely linked to obesity and obesity-related comorbidities; therefore, immune cells have become an important topic in obesity research. Here, we performed a deep phenotypic characterization of circulating T cells in people with obesity, using flow cytometry. Forty-one individuals with obesity (OB) and clinical criteria for bariatric surgery were enrolled in this study. We identified and quantified 44 different circulating T cell subsets and assessed their activation status and the expression of immune-checkpoint molecules, immediately before (T1) and 7–18 months after (T2) the bariatric surgery. Twelve age- and sex-matched healthy individuals (nOB) were also recruited. The OB participants showed higher leukocyte counts and a higher percentage of neutrophils. The percentage of circulating Th1 cells were negatively correlated to HbA1c and insulin levels. OB Th1 cells displayed a higher activation status and lower PD-1 expression. The percentage of Th17 and Th1/17 cells were increased in OB, whereas the CD4+ Tregs' percentage was decreased. Interestingly, a higher proportion of OB CD4+ Tregs were polarized toward Th1- and Th1/17-like cells and expressed higher levels of CCR5. Bariatric surgery induced the recovery of CD4+ Treg cell levels and the expansion and activation of Tfh and B cells. Our results show alterations in the distribution and phenotype of circulating T cells from OB people, including activation markers and immune-checkpoint proteins, demonstrating that different metabolic profiles are associated to distinct immune profiles, and both are modulated by bariatric surgery. [ABSTRACT FROM AUTHOR]

Adipose tissue expansion and subsequent metabolic dysfunction has been considered one of the major risk factors for development of cardiometabolic disease. Epicardial adipose tissue (EAT) in particular is a unique subtype of visceral adipose tissue located on the surface of the heart, around the coronary arteries. Due to its proximity, EAT can modulate the local metabolic and immune function of cardiomyocytes and coronary arteries. Several microRNAs have been described as key players in both cardiac and vascular function that when dysregulated will contribute to dysfunction. Here we review the influence of obesity in the crosstalk between specific adipose tissue types, in particular the EAT‐secreted microRNAs, as key modulators of cardiac disease progression, not only as early biomarkers but also as therapeutic targets for cardiometabolic disease. [ABSTRACT FROM AUTHOR]

The increasing prevalence of childhood obesity escalates the risk for related complications. Circulating microRNAs (miRNAs) have been suggested as good predictive markers of insulin resistance in those with obesity. The aim was to identify a circulating miRNA profile that reflects insulin resistance in prepubertal children with obesity. Plasma miRNAs were measured in prepubertal children (n = 63, 5–9 years) using TaqMan Advanced miRNA Human Serum/Plasma plates and then were validated by RT-qPCR. Subjects were divided into normal weight (n = 20, NW) and overweight or obese (n = 43, OW/OB) groups according to their BMI z-scores. The OW/OB group was further subdivided into insulin sensitive or metabolically healthy obese (n = 26, MHO) and insulin resistant or metabolically unhealthy obese (n = 17, MUO) according to HOMA-IR. While no differences were observed in the fasting plasma glucose levels, serum insulin levels were significantly elevated in the OW/OB compared to the NW group. Of 188 screened miRNAs, eleven were differentially expressed between the NW and OW/OB groups. Validation confirmed increased circulating levels of miR-146a-5p and miR-18a-5p in the OW/OB group, which correlated with BMI z-score. Interestingly, miR-146a-5p was also correlated with HOMA-IR index. While only miR-18a-5p was upregulated in the OW/OB children, independently of their degree of insulin sensitivity, miR-146-5p, miR-423-3p and miR-152-3p were associated with insulin resistance. The present study provides evidence of molecular alterations that occur early in life in prepubertal obesity. These alterations may potentially be crucial for targeted prevention or prompt precision therapeutic development and subsequent interventions. [ABSTRACT FROM AUTHOR]