Current Obesity Reports

Abedalqader, Tala; Klim, Joseph; Boutros, Tony; Ghazal, Nour El; Isaac, Juan Ignacio; Robertson, Andrew G.; Kermansaravi, Mohammad; Ghanem, Omar M.

doi: 10.1007/s13679-026-00711-wpmid: 41926006

Purpose of the reviewThe global epidemic of obesity presents a challenge to physicians in all fields, as it impacts multiple organ systems and may hinder access to surgical or therapeutic interventions, yet reservations regarding referral for metabolic and bariatric surgery (MBS) persist. In this narrative review, we aimed to examine emerging evidence guiding the shift of what were once considered contraindications, to indications of MBS and to shed light on the future projections of MBS.Recent findingsThe technical advancements witnessed in the surgical field over the years, as well as the enhancement of preoperative and postoperative patient management, have contributed to significant improvement in the surgical outcomes of MBS. Coupled with the steadily growing body of evidence, the framework of patient selection has shifted and expanded. Additionally, MBS has been increasingly utilized to bridge to other interventions and to improve metabolic dysfunction, regardless of BMI.SummaryMBS has transitioned from being viewed as a last-resort intervention to an effective, evidence-based therapeutic modality for obesity and its related medical conditions.

Angarita-Plánchez, M. Elena; Sánchez-Rodríguez, Paula; Múnera-Rodríguez, Ana M.; Leiva-Castro, Camila; Benítez-Márquez, Juan Manuel; Reina-Pérez, Icíar; Palomares, Francisca; López-Enríquez, Soledad

doi: 10.1007/s13679-026-00716-5pmid: 42101776

Purpose of ReviewThis review examines the current evidence on autophagy dysregulation in obesity and type 2 diabetes mellitus (T2DM), with particular emphasis on its tissue-specific nature and implications for clinical translation.Recent FindingsRecent human and preclinical evidence indicates that autophagic alterations in metabolic disease are not uniformly suppressed but vary according to tissue type and disease stage. In adipose tissue, liver, skeletal muscle, pancreatic β cells, and immune cells, dysregulated mTORC1-AMPK signaling, defective mitophagy, and impaired lysosomal function contribute to insulin resistance, ectopic lipid accumulation, and metaflammation. However, most human studies rely on static markers such as LC3, p62, and Beclin-1, which do not reliably reflect dynamic autophagic flux. Recent advances, including organelle-specific biomarkers, ex vivo functional assays, and circulating exosomal cargo, offer new translational opportunities, although standardization remains limited.SummaryAutophagy in metabolic disease represents a context-dependent maladaptation rather than a uniformly protective pathway. Future progress will depend on harmonized biomarker panels, functional assessment of autophagic flux in humans, and integration with metabolic phenotyping to enable precision-based therapeutic strategies.

Wang, Ning; Zhang, Jingxing; Zhang, Xinping; Xuan, Dajun

doi: 10.1007/s13679-025-00683-3pmid: 41504957

Purpose of ReviewThis review provides an up-to-date overview of molecular mechanisms and translational potential of N-lactoyl-phenylalanine (Lac-Phe), highlighting recent advances and suggesting future research directions.Recent FindingsRecent studies have revealed the neurobiological mechanism of Lac-Phe, demonstrating its ability to suppress appetite through KATP channel-mediated inhibition of hypothalamic AgRP neurons. Furthermore, emerging research has highlighted its therapeutic potential in type 2 diabetes, inflammatory bowel disease, and spinal cord injury through metabolic and anti-inflammatory pathways.SummaryCurrent evidence establishes Lac-Phe as an exercise-responsive metabolite that suppresses appetite and correlates with exercise intensity, metformin use, and multiple disease states. Its biosynthesis via intestinal CNDP2 and appetite suppression through hypothalamic AgRP neuron inhibition are elucidated. However, clarifying its brain transporters, pharmacokinetics, and the discrepancy between its strong correlation with insulin resistance in healthy individuals and its role as a mediator of metformin’s weight loss effect will be essential to evaluate the diagnostic and therapeutic potential of Lac-Phe.

O’Rourke, Nicholas; Marderfeld, Luba; Dantas, Arthur; Corson, Abbey E.; MacDonald, Meaghan; Ferraro, Zachary M.; Nagpal, Taniya S.; Adamo, Kristi B.

doi: 10.1007/s13679-025-00677-1pmid: 41484833

Purpose of ReviewObesity in childhood remains a critical public health issue, with emerging evidence highlighting developmental origins rooted in parental behaviours before conception. While diet and weight status of birthing parents are well-established predictors of offspring health, the role of preconception physical activity (PA) remains understudied. This scoping review synthesizes current evidence between preconception PA and its association with adverse birth outcomes, and downstream infant and child obesity outcomes, contextualizing findings within the broader parental lifestyle influence. A systematic literature search across ten databases identified 41 relevant studies, predominantly cohort designs, analyzing PA effects on birth weight, gestational diabetes mellitus (GDM), excessive gestational weight gain (eGWG), and offspring adiposity.Recent FindingsFindings revealed no consistent association between preconception PA and birth weight or preterm birth risk. However, studies suggest that preconception PA may lower the likelihood of GDM and eGWG, both of which are linked to increased obesity risk in offspring. A significant methodological limitation across studies was the widespread temporal discontinuity, with PA predominantly assessed through retrospective recall rather than objective measures. Additionally, inconsistencies in study design, PA intensity definitions, and confounding lifestyle factors limit definitive conclusions. SummaryWhile obesity in birthing parents and suboptimal feeding practices dominate current etiological models, the potential preventive role of preconception PA warrants further investigation. Future research should implement intervention designs incorporating objective PA measures (e.g., accelerometry, wearable sensors) within life-course frameworks. Methodologically rigorous studies are critical for disentangling PA-specific effects from confounding lifestyle factors to inform evidence-based guidelines for preconception care.

González-González, Alicia; Soria-Utrilla, Virginia; Fontalba-Romero, María Isabel; Núñez-Sánchez, María Ángeles; Adarve-Castro, Antonio; Queipo-Ortuño, María Isabel; Ramos-Molina, Bruno; Martínez-Montoro, José Ignacio; Fernández-García, José Carlos

doi: 10.1007/s13679-026-00694-8pmid: 41779349

BackgroundMetabolic dysfunction–associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is strongly linked to obesity, type 2 diabetes, and cardiovascular disease. Growing evidence highlights the role of the gut–liver axis, particularly microbial metabolites such as the short-chain fatty acid (SCFA) butyrate, in MASLD pathophysiology. However, clinical data on butyrate levels and the abundance of butyrate-producing bacteria in MASLD patients remain inconsistent.ObjectivesTo systematically synthesize human evidence evaluating the associations between butyrate levels and butyrate-producing gut bacteria with MASLD presence and severity, as well as related metabolic comorbidities.MethodsA systematic search was conducted in PubMed and Embase from inception to April 7, 2025, following PRISMA 2020 guidelines (PROSPERO registration CRD420251162439). Eligible studies included observational human research assessing fecal or plasma SCFA concentrations and/or the abundance of butyrate-producing taxa in adults with MASLD and related metabolic disorders. Study quality was appraised using the Newcastle–Ottawa Scale, and results were narratively synthesized due to heterogeneity across methods and outcomes.ResultsFrom 233 records, seven studies met inclusion criteria (2020–2025; n = 1,185). Most were cross-sectional or case–control designs of moderate to high quality (NOS 6–8/9). Individuals with MASLD generally exhibited lower fecal or serum butyrate concentrations and reduced abundance of Faecalibacterium prausnitzii, Eubacterium, and other butyrate-producing bacteria versus controls. These alterations were associated with hepatic steatosis, fibrosis, inflammation, and adverse metabolic profiles - higher BMI, insulin resistance, and dyslipidemia. Geographic and sex-related differences were also reported.ConclusionsThis systematic review suggests that reduced butyrate availability and alterations in butyrate-producing gut taxa are associated with MASLD presence and severity and with adverse metabolic traits. However, substantial methodological heterogeneity and the observational design of available studies preclude causal inference. Larger, well-phenotyped, multicentre studies using standardized SCFA quantification, dietary and medication ascertainment, and functional microbiome profiling are needed to validate these findings and clarify their diagnostic and therapeutic implications.Graphical Abstract[graphic not available: see fulltext]

Chalotra, Rishabh; Gupta, Tanya; Kumar, Abhitinder; Gupta, Anjali; Kumar, Shivam; Singh, Thakur Gurjeet; Singh, Randhir

doi: 10.1007/s13679-026-00686-8pmid: 41661460

Purpose of ReviewThis review aims to discuss emerging therapeutic strategies for managing Metabolic Syndrome (MetS) by focusing on modulating the gut microbiota using prebiotics, probiotics, and postbiotics, emphasizing their mechanistic roles in restoring metabolic balance and improving host metabolic health.Recent FindingsThe biotics exert various pharmacological effects in restoring gut health and managing MetS by modulating multiple gut-system axes, including the gut-brain axis, gut-liver axis, gut-immune axis, and gut-endocrine axis. Through these mechanisms, they influence satiety regulation, insulin sensitivity, bile acid metabolism, systemic inflammation, and overall energy homeostasis, thereby contributing in the management of MetS.SummaryThis review categorizes therapeutic biotics into three distinct classes: Prebiotics, which serve as substrates to stimulate beneficial bacteria; Probiotics, which supplement the gut with live beneficial microorganisms; and Postbiotics, which are bioactive microbial byproducts that directly modulate host metabolism. Conventional therapies for MetS address individual conditions rather than the syndrome comprehensively, which can promote adverse drug reactions. Whereas, biotic interventions target gut microbiota, a central regulator of energy balance, metabolic signalling and systemic inflammation. By restoring microbial composition and function, these biotics can simultaneously improve insulin sensitivity, reduce inflammation, regulate appetite, and modulate lipid and bile acid metabolism. This multi-dimensional modulation offers biotics as a promising adjunct or complementary strategy, capable of addressing the underlying dysregulation in MetS and offering a more integrative and mechanistic approach to its prevention and management.Graphical Abstract[graphic not available: see fulltext]

Xie, Jiayan; Yang, Yujing; Chen, Wanting; Wang, Lu; Weng, Siying; Lyu, Qiang; Cao, Gang

doi: 10.1007/s13679-026-00722-7pmid: 42249250

Purpose of ReviewObesity stems from a chronic imbalance between energy intake and expenditure. Current therapeutic strategies primarily focus on reducing caloric intake, yet their long-term efficacy is often limited by compensatory metabolic adaptations that lead to weight regain. This review outlines the neural mechanisms through which the central nervous system regulates appetite and the peripheral metabolic pathways that drive adipose thermogenesis. Furthermore, it examines how integrated approaches—spanning from approved to preclinical and clinical-stage investigational agents (e.g., dual- or multi-target agonists), microbiome-targeted interventions (e.g., probiotics), and exercise therapy—can synergistically overcome the limitations of single-pathway strategies. Ultimately, this review provides a theoretical foundation for designing next-generation, personalized, multimodal obesity management regimens.Recent FindingsTraditional weight-loss drugs primarily act by centrally suppressing appetite, reducing food intake through modulation of neural circuits in regions such as the hypothalamus. However, studies show that relying on appetite suppression often triggers compensatory metabolic adaptation, ultimately leading to weight regain. Current anti-obesity drug development is therefore shifting toward integrated central-peripheral dual mechanisms. GLP‑1/glucagon dual-receptor agonists and triple-receptor agonists (such as retatrutide) have exhibited unprecedented weight-loss efficacy in clinical trials. These novel agents overcome the limitations of single-target appetite suppression by synergistically integrating central anorexigenic signaling with peripherally mediated increases in energy expenditure, thereby achieving more potent and durable weight reduction.SummaryThe sustainability of obesity treatment relies on a dual-pronged intervention strategy: suppressing appetite to reduce energy intake while actively promoting energy expenditure, thereby overcoming the metabolic adaptation and weight rebound associated with monotherapy.

Rocha, Sílvia; Proença, Carina; Carvalho, Félix; Fernandes, Eduarda

doi: 10.1007/s13679-026-00733-4pmid: N/A

Purpose of ReviewThis review provides an overview of adipose tissue plasticity and adipogenesis as central processes regulating adipose tissue expansion, remodeling, and metabolic function in health and obesity, highlighting their relevance as potential therapeutic targets.Recent FindingsAdipogenesis is a tightly regulated process involving the differentiation of adipose progenitor cells into mature adipocytes through coordinated transcriptional cascades, primarily driven by peroxisome proliferator–activated receptor (PPAR)γ and CCAAT/enhancer–binding protein (C/EBP) family members. This process is further modulated by multiple signaling pathways, including wingless–related integration site (Wnt), bone morphogenetic proteins (BMPs), and insulin signaling, which collectively regulate adipocyte differentiation and metabolic function. Under physiological conditions, the adipose tissue exhibits remarkable plasticity, with adipogenesis supporting lipid buffering capacity and tissue renewal. In obesity, however, chronic nutrient excess and hormonal dysregulation impair this process, favoring adipocyte hypertrophy, hypoxia, and chronic inflammation. These alterations disrupt adipokine secretion and promote ectopic lipid deposition, thereby contributing to metabolic disorders, including insulin resistance and cardiometabolic disease.SummaryAdipose tissue plasticity and adipogenesis are critical determinants of metabolic health. Dysregulation of these processes underlies adipose tissue dysfunction and contributes to the development of obesity-related comorbidities. Targeting adipogenesis and promoting healthy adipose tissue remodeling represent promising strategies for restoring metabolic homeostasis and mitigating obesity-associated diseases.

Feijó, Mariana; Fonseca, Lara R. S.; Kiss-Toth, Endre; Socorro, Sílvia; Correia, Sara

doi: 10.1007/s13679-026-00690-ypmid: 41739363

Purpose of ReviewThis review addresses the contribution of obesogenic endocrine-disrupting chemicals (EDCs) to prostate carcinogenesis. It provides an in-depth overview of obesogens, tracing their mechanisms of action and effects impacting prostate cell fate. The direct effects of obesogens in disrupting adipose tissue and metabolic homeostasis, as well as disturbing prostate cells, are discussed, along with the potential indirect effects mediated by the dysregulation of the adipose tissue.Recent FindingsObesogens represent a group of EDCs that interfere with endocrine and metabolic processes, underpinning the spread of obesity. Moreover, the ubiquitous presence in the environment, the ability to accumulate in adipose tissue and the broad range of effects targeting several biological pathways highlight that obesogens can be detrimental to human health beyond their action on promoting obesity. Prostate cancer (PCa) is a hormone-dependent cancer for which environmental influences and obesity are established risk factors, with emerging evidence suggesting that obesogens may affect its development and progression.SummaryThe available data indicate that obesogens may contribute to the development of PCa. They can have direct actions in prostate cells modulating signalling pathways that drive tumour aggressiveness. Moreover, the adipose tissue dysregulated by obesogens can acquire an obesity-like phenotype, which may play a crucial role in facilitating tumour growth. Further research is needed to clarify the liaison between obesogen-induced dysregulation of the periprostatic adipose tissue depot and PCa aggressiveness. Unravelling this complex crosstalk will be pivotal for identifying novel therapeutic strategies and preventing aggressive PCa, especially in obese patients.