The recent pandemic Sars-CoV2 infection and studies on previous influenza epidemic have drawn attention to the association between the obesity and infectious diseases susceptibility and worse outcome. Metabolic complications, nutritional aspects, physical inactivity, and a chronic unbalance in the hormonal and adipocytokine microenvironment are major determinants in the severity of viral infections in obesity. By these pleiotropic mechanisms obesity impairs immune surveillance and the higher leptin concentrations produced by adipose tissue and that characterize obesity substantially contribute to such immune response dysregulation. Indeed, leptin not only controls energy balance and body weight, but also plays a regulatory role in the interplay between energy metabolism and immune system. Since leptin receptor is expressed throughout the immune system, leptin may exert effects on cells of both innate and adaptive immune system. Chronic inflammatory states due to metabolic (i.e., obesity) as well as infectious diseases increase leptin concentrations and consequently lead to leptin resistance further fueling inflammation. Multiple factors, including inflammation and ER stress, contribute to leptin resistance. Thus, if leptin is recognized as one of the adipokines responsible for the low grade inflammation found in obesity, on the other hand, impairments of leptin signaling due to leptin resistance appear to blunt the immunologic effects of leptin and possibly contribute to impaired vaccine-induced immune responses. However, many aspects concerning leptin interactions with inflammation and immune system as well as the therapeutical approaches to overcome leptin resistance and reduced vaccine effectiveness in obesity remain a challenge for future research.

Adipose tissue (AT) dysregulation is a key process in the pathophysiology of obesity and its cardiometabolic complications, but even if a growing body of evidence has been collected over recent decades, the underlying molecular basis of adiposopathy remains to be fully understood. In this context, mitochondria, the intracellular organelles that orchestrate energy production and undergo highly dynamic adaptive changes in response to changing environments, have emerged as crucial regulators of both white (WAT) and brown adipose tissue (BAT) metabolism and function. Given that the gut microbiota and its metabolites are able to regulate host metabolism, adipogenesis, WAT inflammation, and thermogenesis, we hypothesize that their frequently observed dysregulation in obesity could affect AT metabolism by exerting direct and indirect effects on AT mitochondria. By collecting and revising the current evidence on the connections between gut microbiota and AT mitochondria in obesity, we gained insights into the molecular biology of their hitherto largely unexplored crosstalk, tracing how gut microbiota may regulate AT mitochondrial function.

Purpose of Review: In this review, we summarize the molecular effects of time-restricted eating (TRE) and its possible role in appetite regulation. We also discuss the potential clinical benefits of TRE in obesity. Recent Findings: TRE is an emerging dietary approach consisting in limiting food intake to a specific window of time each day. The rationale behind this strategy is to restore the circadian misalignment, commonly seen in obesity. Preclinical studies have shown that restricting food intake only during the active phase of the day can positively influence several cellular functions including senescence, mitochondrial activity, inflammation, autophagy and nutrients’ sensing pathways. Furthermore, TRE may play a role by modulating appetite and satiety hormones, though further research is needed to clarify its exact mechanisms. Clinical trials involving patients with obesity or type 2 diabetes suggest that TRE can be effective for weight loss, but its broader effects on improving other clinical outcomes, such as cardiovascular risk factors, remain less certain. Summary: The epidemic proportions of obesity cause urgency to find dietary, pharmacological and surgical interventions that can be effective in the medium and long term. According to its molecular effects, TRE can be an interesting alternative to caloric restriction in the treatment of obesity, but the considerable variability across clinical trials regarding population, intervention, and follow-up duration makes it difficult to reach definitive conclusions.

Background: Age over 50, menopause, obesity and type 2 diabetes (T2D) are key risk factors for Metabolic dysfunction-associated steatotic liver disease (MASLD). This observational study aimed to assess sex differences in anthropometric and clinical profile, including non-invasive liver steatosis indices, in subjects with MASLD, obesity and/or T2D, aged ≥ 50 years. Methods: Anthropometric and clinical parameters, non-invasive indices for steatosis and fibrosis and FibroScan^® data were collected. Results: Among 213 patients (65.7% women, median age 63.0 years and mean Body Mass Index (BMI 34.9 kg/m²), men had higher body weight and waist circumference (WC), whereas women showed higher BMI and waist-to-height ratio (WHtR), and were more likely to exceed WC sex-specific and WHtR risk cut-offs. While transaminases values were higher in men, sex-specific cut-offs revealed that women more frequently exceeded these thresholds. No sex-differences were found for Fatty Liver Index (FLI), Fibrosis-4 (FIB-4) or FibroScan^®, although higher rate of mild fibrosis in women. The diagnostic accuracy of FLI for detecting steatosis was significantly higher in men and unsatisfactory in women (Area Under the ROC Curve, AUC 0.863 vs. 0.655). Conclusions: While MASLD is more common in men, these results suggest that postmenopausal women with visceral obesity showed similar or worse liver and cardiometabolic profiles than men, despite appearing healthier based on standard clinical parameters. Notably, common markers like transaminases and the FLI were less accurate in detecting steatosis in women, underscoring the need for sex-specific diagnostic criteria and greater clinical attention to older women, particularly those with central obesity, to ensure early identification and management of MASLD.

Bariatric surgery (BS) is the most effective treatment in reducing weight and the burden of comorbidities in patients with severe obesity. Despite the overall low mortality rate, intra- and post-operative complications remains quite common. Weight loss before BS reduces surgical risk, but studies are inconclusive regarding which is the best approach to apply. In this review, we summarize the current evidence on the effect of a ketogenic diet (KD) before BS. All studies agree that KD leads to considerable weight loss and important improvements in terms of surgical risk, but populations, interventions and outcomes are very heterogeneous. KD appears to be a safe and effective approach to induce weight loss before BS. However, randomized controlled trials with better-defined dietary protocols and homogeneous outcomes are necessary in order to draw firm conclusions.

In the past two pandemic years, Emergency Departments (ED) have been overrun with COVID-19-suspicious patients. Some data on the role played by laboratory biomarkers in the early risk stratification of COVID-19 patients have been recently published. The aim of this study is to assess the potential role of the new biomarker mid-regional proadrenomedullin (MR-proADM) in stratifying the in-hospital mortality risk of COVID-19 patients at the triage. A further goal of the present study is to evaluate whether MR-proADM together with other biochemical markers could play a key role in assessing the correct care level of these patients. Data from 321 consecutive patients admitted to the triage of the ED with a COVID-19 infection were analyzed. Epidemiological; demographic; clinical; laboratory; and outcome data were assessed. All the biomarkers analyzed showed an important role in predicting mortality. In particular, an increase of MR-proADM level at ED admission was independently associated with a threefold higher risk of IMV. MR-proADM showed greater ROC curves and AUC when compared to other laboratory biomarkers for the primary endpoint such as in-hospital mortality, except for CRP. This study shows that MR-proADM seems to be particularly effective for early predicting mortality and the need of ventilation in COVID-19 patients admitted to the ED.