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Background: The novel liver-gut hormone liver-expressed antimicrobial peptide-2 (LEAP2) is a centrally acting inverse agonist, and competitive antagonist of orexigenic acyl ghrelin (AG), at the GH secretagogue receptor, reducing food intake in rodents. In humans, the effects of LEAP2 on eating behavior and mechanisms behind the postprandial increase in LEAP2 are unclear, though this is reciprocal to the postprandial decrease in plasma AG., Methods: Plasma LEAP2 was measured in a secondary analysis of a previous study. Twenty-two adults without obesity attended after an overnight fast, consuming a 730-kcal meal without or with subcutaneous AG administration. Postprandial changes in plasma LEAP2 were correlated with postprandial changes in appetite, high-energy (HE) or low-energy (LE) food cue reactivity using functional magnetic resonance imaging, ad libitum food intake, and plasma/serum AG, glucose, insulin, and triglycerides., Results: Postprandial plasma LEAP2 increased by 24.5% to 52.2% at 70 to 150 minutes, but was unchanged by exogenous AG administration. Postprandial increases in LEAP2 correlated positively with postprandial decreases in appetite, and cue reactivity to HE/LE and HE food in anteroposterior cingulate cortex, paracingulate cortex, frontal pole, and middle frontal gyrus, with similar trend for food intake. Postprandial increases in LEAP2 correlated negatively with body mass index, but did not correlate positively with increases in glucose, insulin, or triglycerides, nor decreases in AG., Conclusions: These correlational findings are consistent with a role for postprandial increases in plasma LEAP2 in suppressing human eating behavior in adults without obesity. Postprandial increases in plasma LEAP2 are unrelated to changes in plasma AG and the mediator(s) remain uncertain., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Unhealthy alcohol consumption is a global health problem. Adverse individual, public health, and socioeconomic consequences are attributable to harmful alcohol use. Epidemiological studies have shown that alcohol use disorder (AUD) and alcohol-associated liver disease (ALD) are the top two pathologies among alcohol-related diseases. Consistent with the major role that the liver plays in alcohol metabolism, uncontrolled drinking may cause significant damage to the liver. This damage is initiated by excessive fat accumulation in the liver, which can further progress to advanced liver disease. The only effective therapeutic strategies currently available for ALD are alcohol abstinence or liver transplantation. Any molecule with dual-pronged effects at the central and peripheral organs controlling addictive behaviors and associated metabolic pathways are a potentially important therapeutic target for treating AUD and ALD. Ghrelin, a hormone primarily derived from the stomach, has such properties, and regulates both behavioral and metabolic functions. In this review, we highlight recent advances in understanding the peripheral and central functions of the ghrelin system and its role in AUD and ALD pathogenesis. We first discuss the correlation between blood ghrelin concentrations and alcohol use or abstinence. Next, we discuss the role of ghrelin in alcohol-seeking behaviors and finally its role in the development of fatty liver by metabolic regulations and organ crosstalk. We propose that a better understanding of the ghrelin system could open an innovative avenue for improved treatments for AUD and associated medical consequences, including ALD., (© 2022 Research Society on Alcoholism.)

Background: Increased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes., Methods: We included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes., Results: EAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95% CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4 C severity score, independent of obesity. EAT mediated 13.1% (95% CI 3.67-28.0%) and 5.1% (95% CI 0.19-14.0%) of the effect of age and 19.4% (95% CI 4.67-63.0%) and 12.8% (95% CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19., Conclusion: EAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Obesity increases the risk of heart failure (HF), which continues to be a significant proportion of all cardiovascular diseases and affects increasingly younger populations. The cross-talk between adipose and the heart involves insulin resistance, adipokine signaling and inflammation, with the capacity of adipose tissue to mediate hemodynamic signals, promoting progressive cardiomyopathy. Areas covered: From a therapeutic perspective, there is not yet a single obesity-related pathway that when addressed, can ameliorate cardiomyopathy in obese patients and this is a matter of ongoing research. There is poor evidence of the beneficial long-term effect of small nonsurgical intentional weight loss on HF outcomes, in contrast to the field of HF accompanying severe obesity where observational studies have shown that bariatric surgery is associated with improved cardiac structure/function in severely obese patients with HF and preserved ejection fraction (HFpEF) as well as with improved cardiac structure/function in those with HF and reduced ejection fraction (HFrEF). Few studies report positive outcomes in subjects with obesity and HF, both severe, who underwent bariatric surgery as a rescue treatment, including bridge to heart transplantation. Expert commentary: The fast growing prevalence of obesity will continue to require the development of appropriate interventions directed at controlling or slowing pathways of cardiac damage in these patients, but at present, bariatric surgery should be considered an option to try to decrease morbidity associated with HF in severely obese adults.

Background: Body mass index (BMI) ≥50.0 kg/m 2 has been associated with increased surgical complications and mortality. We assessed echocardiographic characteristics and bariatric surgery complications of patients with BMI ≥50.0 kg/m 2 vs. those in less severe obesity., Methods and Results: A retrospective analysis in patients who underwent gastric bypass was performed. Pre-surgery structural characteristics analyzed included left atrial dimension (LA), left ventricle mass (LVM), LVM indexed for height 2.7 (LVMI), and LV hypertrophy (LVH). Functional characteristics included LV diastolic and systolic function. Degree of obesity was correlated with cardiac parameters, comorbidities, and surgical complications. Data on 312 patients (75.3 % women, age 39.3 ± 0.6 years, BMI 50.2 ± 0.5 kg/m 2 ) were analyzed. Cardiac parameters on the basis of BMI (<50 kg/m 2 vs. ≥50 kg/m 2 ) were LA 39.6 ± 4.8 vs. 41.9 ± 5.2 mm, LVM 161 ± 46 vs. 194 ± 56 g, LVMI 43.6 ± 0.9 vs. 51.8 ± 1.3 g/ht 2.7 , and systolic pulmonary pressure 43.7 ± 10.1 vs. 50.5 ± 11.3 mmHg, respectively (all p < 0.001). LVMI was correlated with BMI (p < 0.001), 2-h glucose on a glucose tolerance test (p = 0.01), and ejection fraction (p = 0.01). Surgical complications were not different among groups. Presence of LVH was independently associated with BMI ≥50 kg/m 2 and female sex, after adjusting for age, diabetes, hypertension, and pulmonary hypertension., Conclusion: Body mass index ≥50 kg/m 2 was independently associated with female sex and LVH but not with hypertension, diabetes, or a higher rate of surgical complications.

Objective. To examine the frequency and patterns of association of cardiovascular risk factors with atherosclerosis in five different arterial territories at post-mortem in Mexico City. Methods. We obtained five arterial territories arteries (circle of Willis, coronary, carotid, renal, and aorta) of 185 men and women 0 to 90 years of age who underwent autopsy at the Medical Forensic Service of Mexico City. We determined the prevalence and extent of atherosclerotic lesions by histopathology according to the classification of the American Heart Association as early (types I-III) and advanced (types IV-VI), and according to the degree of stenosis and correlated with cardiovascular risk factors. Results. Atherosclerotic lesions were identified in at least one arterial territory in 181 subjects (97.8%), with involvement of two ore more territories in 178 subjects (92.2%). Advanced lesions were observed in 36% and 67% of subjects under 15 and between 16 and 35 years, respectively. Any degree of atherosclerosis was associated with the presence of diabetes mellitus, hypertension, overweight, obesity, and smoking, and to a greater extent with the presence of two or more risk factors (P < 0.001). However, emerging and advanced athersoclerosis was observed in 53% and 20% people with no risk factors. Conclusions. The study shows a high prevalence of atherosclerosis in all age groups and both sexes. There is considerable development of atherosclerotic disease in subjects without known risk factors.