Steatotic liver disease (SLD) comprises metabolic dysfunction-associated SLD, metabolic and alcohol-related liver disease, and alcohol-related liver disease, conditions that frequently overlap rather than fall into distinct categories. Cardiometabolic risk factors (CMRFs), including obesity, type 2 diabetes, hypertension and dyslipidaemia, are highly prevalent across SLD subtypes, with most patients exhibiting multiple metabolic abnormalities. These risks interact synergistically with alcohol exposure, accelerating fibrosis progression to cirrhosis and liver mortality. Importantly, both alcohol consumption and metabolic risks are dynamic and can fluctuate over time, leading to transitions across the SLD spectrum that static diagnostic thresholds might not adequately capture. Misclassification is common, particularly due to under-reporting of alcohol intake, underscoring the value of objective alcohol biomarkers such as phosphatidylethanol. Accurate risk stratification, therefore, requires an integrated approach combining systematic alcohol screening, structured evaluation of CMRFs and non-invasive fibrosis assessment. Management must be multidisciplinary, combining alcohol reduction strategies, optimization of metabolic control and liver-directed therapies. However, most emerging pharmacotherapies for metabolic dysfunction-associated steatohepatitis exclude individuals with concurrent alcohol use, creating a gap between clinical trial populations and real-world practice. A dynamic, spectrum-based framework incorporating repeated reassessment of alcohol and metabolic risks offers the most pragmatic path for diagnosis, treatment and equitable care delivery in SLD.

The Lipid Accumulation Product (LAP) is recognized as an indicator of lipid-induced cellular stress. While its predictive value for conditions like diabetes, liver disease, and metabolic syndrome is established, its specific correlations with individual metabolic and hematological markers within the context of obesity remain less defined. This study sought to comprehensively investigate the links between LAP and a spectrum of metabolic and hematological biomarkers in individuals with obesity. This cross-sectional study involved 304 obese participants. Standard anthropometric measurements [weight, height, waist and hip circumference (WC, HC)] were taken, and dietary intake was assessed via a food frequency questionnaire. Blood samples were analyzed for glucose, insulin, hemoglobin A1C, serum lipids [total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C)], and a complete blood cell count. LAP was calculated using WC and triglyceride levels. Participants were categorized into three tertiles based on their LAP values. Individuals in the highest LAP tertile had significantly higher body weight, body mass index, WC, and waist-to-hip ratio than those in the lowest tertile (all P < 0.05). Higher LAP tertiles were also associated with increased systolic and diastolic blood pressure, total cholesterol, triglycerides, and reduced HDL-C levels after adjustment for potential confounders. In addition, white blood cell count and mean corpuscular hemoglobin remained significantly higher across LAP tertiles in the fully adjusted models. Supplementary receiver operating characteristic (ROC) analysis demonstrated good discriminatory performance of LAP for identifying metabolic syndrome (AUC = 0.833; 95% CI: 0.779-0.887). Higher LAP was independently associated with an adverse cardiometabolic profile, characterized by greater adiposity, unfavorable lipid parameters, elevated blood pressure, and selected hematological alterations in adults with obesity. These findings support the potential utility of LAP as a simple and accessible marker for identifying individuals at increased cardiometabolic risk. However, prospective studies are needed to determine its predictive value and establish temporal relationships.

Glucagon-like peptide-1 receptor agonists are transforming cardiometabolic care, yet their expanding use in older adults raises an overlooked question: can cardiovascular and renal protection come at the expense of muscle mass, nutritional resilience, and independence? We propose a geriatric-informed prescribing framework that redefines treatment success beyond weight loss.

Cardiometabolic risk is increasingly recognised as a significant and evolving health concern within the cystic fibrosis (CF) population. Although nutrition has long been central to CF management, its broader influence on cardiometabolic health, well established in the general population, is only beginning to be understood in the context of CF. This narrative review seeks to synthesise emerging evidence and highlight the key research gaps relating to the role of nutrition in moderating cardiometabolic risk among people with CF (pwCF). Substantial gaps remain across several domains, including overweight and obesity, dysglycaemia and diabetes, cardiovascular disease, gut microbiota alterations and overall diet quality. Addressing these gaps is essential as pwCF live longer and encounter new health challenges. Future nutrition research must generate the robust, clinically relevant evidence needed to support clinical teams as they transition away from traditional dietary paradigms, enabling the development of updated guidance and the advancement of clinical practice toward metabolically informed, contemporary models of care.

Psychiatric disorders are highly prevalent among individuals living with obesity and contribute to treatment resistance, poor adherence, and adverse health outcomes. Yet, obesity management often remains fragmented, with limited integration between endocrinology, psychiatry, and behavioral health. This Perspective advocates for a mental health framework for obesity care. We emphasize the need for future investigations to test the clinical relevance of behavioral phenotyping as a complementary approach to pharmacotherapy, including GLP-1 receptor agonists, to enhance treatment personalization. By reframing obesity as a disease deeply intertwined with mental health, we emphasize the need for multidisciplinary care models that incorporate psychological assessment, stigma reduction, and patient-centered nutrition counseling. Advancing this framework will require closer collaboration between medical and mental health disciplines and greater investment in neurobehavioral research to improve long-term outcomes in obesity care.

This chapter presents a comprehensive overview of central sleep apnea (CSA) and central hypoventilation disorders in the pediatric population. It places particular emphasis on children with complex medical conditions and genetic syndromes, including congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome.In addition, the chapter examines related conditions such as Prader-Willi syndrome and other hypoventilation disorders arising from structural or functional abnormalities, including Chiari malformations and Leigh syndrome. It reviews current knowledge of the pathogenesis, epidemiology, clinical presentation, and diagnostic evaluation of these disorders in children, and concludes with evidence-based guidance for their management and treatment.

Adipose tissue protects metabolic homeostasis by storing excess fatty acids, releasing fuels during energy demand and coordinating endocrine and inflammatory signals. These functions are often described as linear pathways of lipogenesis, lipolysis, fatty acid oxidation and thermogenesis. However, lipid handling in adipocytes is spatially organized by organelle contact sites. The endoplasmic reticulum (ER), lipid droplets (LDs), mitochondria, peroxisomes and lysosomes form dynamic interfaces that determine whether fatty acids are stored safely, mobilized for oxidation, processed into specialized lipid species or redirected toward lipotoxic intermediates. In this review, we synthesize evidence that ER-LD and LD-mitochondria contacts coordinate lipid storage and oxidative use, whereas peroxisome-centred contacts connect lipolysis, very-long-chain and branched-chain fatty acid processing, plasmalogen metabolism and mitochondrial remodelling. We further discuss how autophagy and lysosomal pathways maintain adipocyte quality control by regulating LD turnover, mitophagy and membrane renewal. Finally, we propose that obesity, insulin resistance, ectopic lipid deposition, lipodystrophy and adipose inflammation can be viewed as different manifestations of impaired spatial lipid routing. This framework does not replace classical metabolic models, but provides a mechanistic layer that may help identify contact-site-dependent vulnerabilities in metabolic disease.

This study aimed to synthesize and quantitatively assess the available evidence on the effects of phytosterol supplementation on hepatic lipid metabolism and obesity-related metabolic outcomes in obese rodent models, integrating biochemical, histological, and molecular evidence. A systematic search was conducted in electronic databases (PubMed, EMBASE, and Web of Science). Data on study design, population, intervention, outcomes, and risk of bias were extracted and analyzed. A quantitative meta-analysis was performed. Meta-analysis showed reductions in body weight, serum triglycerides, total cholesterol, LDL-C, VLDL-C, glucose, liver weight, hepatic cholesterol, hepatic triglycerides, and Non-alcoholic fatty liver disease activity score. No significant changes were observed for adiposity index, HDL-C, insulin, or hepatic expression of PPARα, FAS, and SREBP1c. Conversely, CPT1A expression was significantly increased following PS supplementation. Subgroup analyses indicated that the beneficial effects on lipid and hepatic outcomes were generally consistent across rodent species (mice, rats, and hamsters), obesity induction models, and routes of administration, although the magnitude of responses varied between strains, with C57BL/6 mice showing more pronounced metabolic improvements. Additional analyses suggested that treatment duration and phytosterol composition may modulate specific outcomes, whereas dose-response meta-regression identified dose-dependent associations for serum and hepatic cholesterol, and PPARα expression in dietary supplementation studies. Overall, the available preclinical evidence suggests that phytosterol supplementation may improve several metabolic and hepatic outcomes in rodent models of obesity. However, the substantial heterogeneity across studies highlights the need for standardized experimental protocols and future clinical studies before these findings can be translated to human health.