Aims: Human epicardial adipose tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-protein–coupled receptors, such as those for glucose-dependent insulinotropic polypeptide (GIP), glucagon (GCG), and glucagon-like peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG, and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell-type localization specifically for GIP receptor (GIPR) and glucagon receptor (GCGR). Methods and results: Epicardial adipose tissue samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2 ± 10.5 years mean ± SD). Microarray and immunohistochemistry analyses were performed. Microarray analysis showed that GIPR and GCGR messenger ribonucleic acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1 [3776 ± 1377 arbitrary unit (A.U.), 17.77 ± 14.91 A.U., and 3.41 ± 2.27 A.U., respectively]. The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated, and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in free fatty acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (P < 0.01). Epicardial adipose tissue GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (P < 0.01). Conclusions: Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein–coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.

Objective: The excess of visceral adipose tissue might hinder and delay immune response. How people with abdominal obesity (AO) will respond to mRNA vaccines against SARS‐CoV‐2 is yet to be established. SARS‐CoV‐2‐specific antibody responses were evaluated after the first and second dose of the BNT162b2 mRNA vaccine, comparing the response of individuals with AO with the response of those without, and discerning between individuals with or without prior infection.Methods: Immunoglobulin G (IgG)‐neutralizing antibodies against the Trimeric complex (IgG‐TrimericS) were measured at four time points: at baseline, at day 21 after vaccine dose 1, and at 1 and 3 months after dose 2. Nucleocapsid antibodies were assessed to detect prior SARS‐CoV‐2 infection. Waist circumference was measured to determine AO.Results: Between the first and third month after vaccine dose 2, the drop in IgG‐TrimericS levels was more remarkable in individuals with AO compared with those without AO (2.44‐fold [95% CI: 2.22‐2.63] vs. 1.82‐fold [95% CI: 1.69‐1.92], respectively, p < 0.001). Multivariable linear regression confirmed this result after inclusion of assessed confounders (p < 0.001).Conclusions: The waning antibody levels in individuals with AO may further support recent recommendations to offer booster vaccines to adults with high‐risk medical conditions, including obesity, and particularly to those with a more prevalent AO phenotype.

Purpose Chest X-ray (CXR) severity score and BMI-based obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored. Methods This retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19. Results Patients with abdominal obesity showed significantly higher CXR severity scores and had higher rates of CXR severity scores ≥ 8 compared to those without abdominal obesity (P < 0.001; P = 0.001, respectively). By contrast, patients with normal weight, with overweight and those with BMI-based obesity showed no significant differences in either CXR severity scores or in the rates of CXR severity scores ≥ 8 (P = 0.104; P = 0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity scores than BMI (r = 0.43, P < 0.001; r = 0.41, P < 0.001; r = 0.17, P = 0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were significantly higher than that for BMI in identifying a high CXR severity score (≥ 8) (0.68 [0.60–0.75] and 0.67 [0.60–0.74] vs 0.58 [0.51–0.66], P = 0.001). A multivariate analysis indicated abdominal obesity (risk ratio: 1.75, 95% CI: 1.25–2.45, P < 0.001), bronchial asthma (risk ratio: 1.73, 95% CI: 1.07–2.81, P = 0.026) and oxygen saturation at admission (risk ratio: 0.96, 95% CI: 0.94–0.97, P < 0.001) as the only independent factors associated with high CXR severity scores. Conclusion Abdominal obesity phenotype is associated with a high CXR severity score better than BMI-based obesity in hospitalized patients with COVID-19. Therefore, when visiting the patient in a hospital setting, waist circumference should be measured, and patients with abdominal obesity should be monitored closely. Level of evidence Cross-sectional descriptive study, Level V.