Caloric restriction (CR) promotes longevity and metabolic health by modulating gene expression and cellular processes. However, the role of alternative mRNA splicing in CR-induced metabolic adaptation remains underexplored. In this study, we analyzed RNA sequencing data from the subcutaneous white adipose tissue of CR mice. We identified 6058 differentially expressed genes, with significant upregulation of lipid metabolism pathway genes, such as Elovl6, Fasn, and Srebp1c. We also detected 400 CR-associated alternative splicing events, with the skipped exon and retained intron events predominantly affecting lipid biosynthesis and energy metabolism. Among these events, Ncoa2, a nuclear receptor coactivator involved in lipid metabolism, exhibited increased exon 13 inclusion under CR, favoring the expression of the full-length isoform. Functional assays revealed that full-length NCOA2 enhanced PPARγ-mediated transcriptional activation, while the truncated Δ-NCOA2 isoform exhibited altered coactivator activity. Δ-NCOA2 was found to lack an LXXL motif critical for nuclear receptor interactions, potentially modifying its function. Taken together, these findings indicate that CR-induced alternative splicing fine-tunes metabolic and transcriptional networks, thereby contributing to lipid homeostasis and energy adaptation. Our study highlights a novel regulatory layer by which CR modulates metabolism through coordinated transcriptional and splicing alterations, offering new insights into the molecular mechanisms underlying the beneficial effects of CR on aging and metabolic health. Further investigations are warranted to determine the tissue-specificity of the CR-induced splicing changes and their potential implications for metabolic disorders and lifespan extension.

Adipose tissue represents an organ that is highly dynamic and contributes toward vital survival events such as immune responses, lactation, metabolism fuel, and thermogenesis. Data emerging from recent studies support the notion of adipose tissue being organized into a complex system characterized by a discrete anatomy, elevated physiological plasticity, and specific vascular and nerve supplies. Vasoactive intestinal peptide (VIP), along with its receptors, type 1 (VPAC1) and type 2 (VPAC2), has been implicated in various physiological and pathophysiological processes. However, studies on VIP and its receptors in adipose tissue are limited. To explore VIP's presence and activity, as well as its adipose tissue-based receptors, we conducted a study on isolated adipocytes and adipose tissue from inguinal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT) in normal and cold-stressed rats. Our findings indicate the presence of the gene expression VIP and VPAC1 in both WAT and BAT under normal conditions, while VPAC2 was absent. In both WAT and BAT, cold exposure upregulated VIP gene expression. However, the response of VIP receptors to cold exposure is controversial. VPAC2 gene expression was induced in both WAT and BAT, while VPAC1 gene expression presented no change of significance in BAT and a slight reduction in WAT. Additionally, VIP, VPAC1, and VPAC2 proteins were identified from Western blot studies on white and brown adipocytes. After exposure to cold there was an increase of significance in the VIP, VPAC1, and VPAC2 protein levels. This study provides novel insights into how VIP and its receptors alter gene expression and protein levels in adipose tissue and adipocytes during cold stress, indicating their potential involvement in adipose tissue regulation. The findings propose VIP's potentially crucial role in adipose tissue's adaptation to cold stress by affecting the metabolic and biochemical functions of subcutaneous and interscapular adipocytes, with potentially significant implications in the context of developing therapies targeting metabolic disorders.

Obesity is a worldwide health crisis and poses significant challenges in critical care. Many studies suggest an 'obesity paradox', in which obesity, defined by body mass index (BMI), is associated with better outcomes. However, the inability of BMI to discriminate between fat and muscle or between visceral adipose tissue and subcutaneous adipose tissue, limits its prediction of metabolic ill health. We suggest that the 'obesity paradox' may be more reflective of the limitations of BMI than the protective effect of obesity. We explore the biological processes leading to visceral fat accumulation, and the evidence linking it to outcomes in critical illness. In the 'spillover' hypothesis of adipose tissue expansion, caloric excess and impaired expansion of storage capacity in the subcutaneous adipose tissue lead to accumulation of visceral adipose tissue. This is associated with a chronic inflammatory state, which is integral to the link between visceral adiposity, type 2 diabetes mellitus, and ischaemic heart disease. We review the current evidence on visceral adiposity and critical illness outcomes. In COVID-19, increased visceral adipose tissue, irrespective of BMI, is associated with more severe disease. This is mirrored in acute pancreatitis, suggesting visceral adiposity is linked to poorer outcomes in some hyperinflammatory conditions. We suggest that visceral adiposity's chronic inflammatory state may potentiate acute inflammation in conditions such as COVID-19 and acute pancreatitis. Further work is required to investigate other critical illnesses, especially sepsis and acute respiratory distress syndrome, in which current evidence is scarce. This may give further insights into pathophysiology and inform tailored treatment and nutrition strategies based on body fat distribution.

Adipocytokines, including leptin, adiponectin, and resistin, are key mediators linking adiposity, insulin resistance, and inflammation. We present the first genome-wide association study (GWAS; N = 5258) and exome-wide association study (ExWAS; N = 4578) on leptin, adiponectin, and resistin in South Asian population. We identified novel associations in genes ZNF467, and LEPREL2 for leptin; ZNF467, LEPREL2, CRLF3, ZNF732, SOX30, XIRP1, ATP8B3, SPATA2L, TMCO4, TLN2, ABCA12, and SHB for adiponectin; and D2HGDH for resistin. Additionally, we confirmed known associations of FTO, MC4R, and HOXB3 with leptin and ADIPOQ with adiponectin. Notably, ADIPOQ variants were consistently significant across GWAS, ExWAS, and gene-based analyses, reinforcing their central role in regulating adiponectin levels. Most of these novel associations identified were population-specific, highlighting the importance of studying diverse populations to uncover unique genetic signals. After adjusting for BMI, the associations with adiponectin and resistin remained significant, whereas most associations for leptin weakened in both effect size and significance. Functional annotation revealed that the identified variants were enriched for expression in adipose tissue, the brain (cerebellar hemisphere and cerebral cortex), and the pituitary gland. These variants act as eQTLs and splice-QTLs in adipose, brain, and pancreas, suggesting cross-tissue regulatory mechanisms. ExWAS further implicated rare variant burden in genes such as LONP1, ZNF335, and TTC16 for adiponectin and resistin. These findings enhance our understanding of adipocytokine biology, emphasises the need for population-specific genetic research, and lays foundation for future functional studies.

IL-1α, IL-1β, IFN-γ, IL-17 and the expression of inducible nitric oxide synthase (iNOS) enzyme by macrophages, which generate nitric oxide, are protective against tuberculosis, a disease caused by Mycobacterium tuberculosis. The severity of tuberculosis can be dependent on bacterial load and/or lung immunopathology. Tuberculosis is aggravated by existing comorbidities such as obesity. Obesity induces metabolic dysfunction, meta inflammation and dysbiosis, which increase the prevalence of respiratory diseases and worsen immunopathology. The deficiency of IL-1α (IL-1α-/-) induces deleterious lung monocytic inflammation and functional activation of the adaptive immune response mediated by T cells during M. tuberculosis infection in non-obese mice. Although iNOS and IFN-γ have been described as protective in experimental tuberculosis, using a model of obesity induced by high-fat diet, we show here an increase in iNOS-expressing interstitial macrophages positively correlated with M. tuberculosis numbers in the lungs of IL-1α-/- animals, followed by increased frequency of IFN-γ and decreased frequency of IL-17-producing T cells, showing that IFN-γ and iNOS contribute to immunopathology and pulmonary damage. The protective effect of IL-1α, characterised by reduction of lung immunopathology, is dependent on IL-17-producing CD4+ cells that negatively regulate iNOS expression on macrophages. Our data provide important implications for tuberculosis with existing obesity that aggravates lung immunopathology associated with an exacerbation of IFN-γ-producing and iNOS-expressing cells.

The purpose of this network meta-analysis (NMA) of randomized controlled trials (RCT) was to examine the effects of different exercise intensities on inflammatory markers in women with overweight/obesity.

A systematic search for RCTs that met the inclusion criteria for the period up to October 2024. random effects NMA was performed within a frequency-based framework.

A total of 75 RCTs were included (3989 participants). High-intensity exercise significantly modulated leptin and adiponectin levels, but had a nonsignificant effect on TNF-α, CRP, and IL-6 levels. Moderate-intensity exercise significantly modulated TNF-α, CRP, IL-6, leptin, and adiponectin levels. Surface under the cumulative ranking curve (SUCRA) probability ranking showed that moderate-intensity exercise was the most recommended exercise intensity for reducing TNF-α, CRP, IL-6, and leptin levels, and for modulating adiponectin levels, moderate-intensity exercise also had a SUCRA value of 65.4%, so we believe that moderate-intensity exercise may be the most robust type of exercise intensity in terms of the breadth of effects. Subgroup analysis showed that moderate-intensity aerobic exercise (MAE) significantly reduced TNF-α levels. Moderate-intensity resistance training (MRT) is the most recommended type for decreasing IL-6 and leptin levels. Moderate-intensity combined exercise (MCE) is the best type of exercise for managing CRP and adiponectin levels.

There were significant differences in the effects of different exercise intensities on specific inflammatory markers in women living with overweight and obesity. Moderate-intensity exercise may be the most robust type of exercise intensity. Future studies should consider the importance of exercise duration and volume (e.g., in MET* minutes/week) to better understand the relationship between exercise intensity and inflammatory markers. The effects of combining exercise and diet on inflammatory markers in women with overweight and obesity should also be explored in greater depth.

A mutualistic co-evolution exists between the host and its associated microbiota in the human body. Bacteria establish ecological niches in various tissues of the body, locally influencing their physiology and functions, but also contributing to the well-being of the whole organism through systemic communication with other distant niches (axis). Emerging evidence indicates that when the composition of the microbiota inhabiting the niche changes toward a pathogenic state (dysbiosis) and interactions with the host become unbalanced, diseases may present. In addition, imbalances within a single niche can cause dysbiosis in distant organs. Current research efforts are focused on elucidating the mechanisms leading to dysbiosis, with the goal of restoring tissue homeostasis. In vitro models can provide critical experimental platforms to address this need, by reproducing the niche cyto-architecture and physiology with high fidelity. This review surveys current in in vitro host-microbiota research strategies and provides a roadmap that can guide the field in further developing physiologically relevant in vitro models of ecological niches, thus enabling investigation of the role of the microbiota in human health and diseases. Lastly, given the Food and Drug Administration Modernization Act 2.0, this review highlights emerging in vitro strategies to support the development and validation of new therapies on the market.

Bile Arisaema, a traditional Chinese medicine, has been previously identified by our team to possess antipyretic properties attributed to its polysaccharide component. Recently, we have confirmed that bile Arisaema played a significantly lipid-lowering effect on hyperlipidemia rats. Building upon this discovery, the present study aimed to investigate the unexplored hypolipidemic potential of its polysaccharide component and elucidate the underlying mechanisms. A soluble polysaccharide fraction devoid of free proteins, named BAPs, was extracted from bile Arisaema using a combination of hot water extraction, alcohol precipitation, and the Sevage method. The structural characteristics of BAPs were preliminarily elucidated through monosaccharide composition analysis (mainly composed of glucose), molecular weight distribution (38.74 kDa and 2.87 kDa), and glycosyl linkage analysis via methylation. The results of animal experiment demonstrated that oral administration of BAPs (400 mg/kg/day) for four weeks significantly improved abnormal serum lipid levels, hepatic function and histopathological injury on high-fat diet-induced hyperlipidemia rats. Mechanistically, the results of high throughput sequencing indicated that BAPs intake markedly altered the hepatic and fecal metabolome and lipidome, while also modulating gut microbiota composition and improving intestinal barrier integrity. Spearman's correlation analysis unveiled closely associations between the altered microbes, lipids, metabolites and serum biochemical indicators. Western blotting and qRT-PCR analyses further confirmed that these metabolic improvements were mediated by the regulation of key genes involved in lipid metabolism. Collectively, this study demonstrated that BAP supplementation effectively improved serum lipid profiles in hyperlipidemia rats by modulating metabolic disorders and restoring gut homeostasis.

Age-related changes in adipose tissue affect chronic medical diseases and mobility disability but mechanism remains poorly understood. The goal of this study is to define methods for phenotyping unique characteristics of adipose tissue from older adults.

Older adults enrolled in study of muscle, mobility, and aging selected for the adipose tissue ancillary (SOMMA-AT; N = 210, 52.38% women, 76.12 ± 4.37 years) were assessed for regional adiposity by whole-body magnetic resonance (AMRA) and underwent a needle-aspiration biopsy of abdominal subcutaneous adipose tissue (ASAT). ASAT biopsies were flash frozen, fixed, or processed for downstream applications and deposited at the biorepository. Biopsy yields, qualitative features, adipocyte sizes, and concentration of adipokines secreted in ASAT explant conditioned media were measured. Inter-measure Spearman correlations were determined.

Regional, but not total, adiposity differed by sex: women had greater ASAT mass (8.20 ± 2.73 kg, p < .001) and biopsy yield (3.44 ± 1.81 g, p < .001) than men (ASAT = 5.95 ± 2.30 kg, biopsy = 2.30 ± 1.40 g). ASAT mass correlated with leptin (r = 0.54, p < .001) and not resistin (p = .248) and adiponectin (p = .353). Adipocyte area correlated with ASAT mass (r = 0.34, p < .001), BMI (r = 0.33, p < .001), adiponectin (r = -0.22, p = .005) and leptin (r = 0.18, p = .024) but not with resistin (p = .490).

In addition to the detailed ASAT biopsy processing in this report, we found that adipocyte area correlated with ASAT mass, and both measures related to some key adipokines in the explant conditioned media. These results, methods, and biological repositories underscore the potential of this unique cohort to impact the understanding of aging adipose biology on disease, disability, and other aging tissues.

Cellular heterogeneity of human adipose tissue is linked to the pathophysiology of obesity and may impact the response to energy restriction and changes in fat mass. Herein, we provide an optimized pipeline to estimate cellular composition in human abdominal subcutaneous adipose tissue (ASAT) bulk RNA sequencing (RNA-seq) datasets using a single-nuclei RNA-seq signature matrix.

A deconvolution pipeline for ASAT was optimized by benchmarking publicly available algorithms using a signature matrix derived from ASAT single-nuclei RNA-seq data from 20 adults and then applied to estimate ASAT cell-type proportions in publicly available obesity and weight loss studies.

Individuals with obesity had greater proportions of macrophages and lower proportions of adipocyte subpopulations and vascular cells compared with lean individuals. Two months of diet-induced weight loss increased the estimated proportions of macrophages; however, 2 years of diet-induced weight loss reduced the estimated proportions of macrophages, thereby suggesting a biphasic nature of cellular remodeling of ASAT during weight loss.

Our optimized high-throughput pipeline facilitates the assessment of composition changes of highly characterized cell types in large numbers of ASAT samples using low-cost bulk RNA-seq. Our data reveal novel changes in cellular heterogeneity and its association with cardiometabolic health in humans with obesity and following weight loss.

The incidence and burden of skin wounds, especially chronic and complex wounds, have a profound impact on healthcare. Effective wound healing strategies require a multidisciplinary approach, and advances in materials science and bioengineering have paved the way for the development of novel wound healing dressing. In this context, electrospun nanofibers can mimic the architecture of the natural extracellular matrix and provide new opportunities for wound healing. Inspired by the bioelectric phenomena in the human body, electrospun nanofibrous scaffolds with electroactive characteristics are gaining widespread attention and gradually emerging. To this end, this review first summarizes the basic process of wound healing, the causes of chronic wounds, and the current status of clinical treatment, highlighting the urgency and importance of wound dressings. Then, the biological effects of electric fields, the preparation materials, and manufacturing techniques of electroactive electrospun nanofibrous (EEN) scaffolds are discussed. The latest progress of EEN scaffolds in enhancing skin wound healing is systematically reviewed, mainly including treatment and monitoring. Finally, the importance of EEN scaffold strategies to enhance wound healing is emphasized, and the challenges and prospects of EEN scaffolds are summarized.

Obesity is a condition of chronic low-grade inflammation affecting peripheral organs of the body, as well as the central nervous system. The adipose tissue dysfunction occurring under conditions of obesity is a key factor in the onset and progression of a variety of diseases, including neurodegenerative disorders. Mitochondria, key organelles in the production of cellular energy, play an important role in this tissue dysfunction. Numerous studies highlight the close link between obesity and adipocyte mitochondrial dysfunction, resulting in excessive ROS production and adipose tissue inflammation. This inflammation is transmitted systemically, leading to metabolic disorders that also impact the central nervous system, where pro-inflammatory cytokines impair mitochondrial and cellular functions in different areas of the brain, leading to neurodegenerative diseases. To date, several bioactive compounds are able to prevent and/or slow down neurogenerative processes by acting on mitochondrial functions. Among these, some molecules present in the Mediterranean diet, such as polyphenols, carotenoids, and omega-3 PUFAs, exert a protective action due to their antioxidant and anti-inflammatory ability. The aim of this review is to provide an overview of the involvement of adipose tissue dysfunction in the development of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and multiple sclerosis, emphasizing the central role played by mitochondria, the main actors in the cross-talk between adipose tissue and the central nervous system.

Cardiometabolic risk and associated dysfunctions contribute largely to the recent rise in mortality globally. Advancements in multi-omics in recent years promise a better understanding of potential biomarkers that enable an early diagnosis of cardiometabolic dysfunction. However, the molecular mechanisms driving the onset and progression of cardiometabolic disorders remain poorly understood. Adipokines are adipocyte-specific cytokines that are central to deleterious cardiometabolic alterations. They exhibit both pro-inflammatory and anti-inflammatory effects, complicating their association with cardiometabolic disturbances. Thus, understanding the cardiometabolic association of adipokines from a molecular and signaling perspective assumes great importance. This review presents a comprehensive outline of the most prominent adipokines exhibiting pro-inflammatory and/or anti-inflammatory functions in cardiometabolic dysfunction. The review also presents an insight into the pathophysiological implications of such adipokines in different cardiometabolic dysfunction conditions, the status of adipokine druggability, and future studies that can be undertaken to address the existing scientific gap. A clear understanding of the functional and mechanistic role of adipokines can potentially improve our understanding of cardiovascular disease pathophysiology and enhance our current therapeutic regimen in the years to come.

Maternal obesity is an escalating public health concern that adversely affects pregnancy outcomes. Adipokines play a key role in regulating metabolism and fetal development, but their dynamic changes during pregnancy remain inadequately understood. Objective: This study investigates maternal and fetal adipokine variations throughout pregnancy and their associations with maternal body mass index (BMI), abdominal wall thickness, and neonatal outcomes. Methods: A prospective case-control study was conducted involving 74 pregnant women categorized by BMI. Maternal blood samples were collected at mid-pregnancy and delivery, and additional analysis of umbilical-cord blood was performed. Clinical parameters such as BMI, abdominal wall thickness, and fetal growth metrics were also recorded. Results: Adiponectin levels were significantly lower in obese pregnancies, whereas leptin and visfatin levels increased with higher maternal BMI. Umbilical-cord blood leptin levels correlated positively with maternal BMI and neonatal birth weight, while ghrelin levels were reduced in neonates born to obese mothers. Significant adipokine fluctuations were observed between mid-pregnancy and delivery. Conclusions: Maternal obesity is associated with distinct alterations in adipokine profiles. These findings highlight the potential of maternal adipokines, given their links to maternal adiposity, as predictive biomarkers for adverse pregnancy outcomes and long-term metabolic risks in offspring. Further interventional research is warranted to evaluate targeted strategies aimed at improving perinatal metabolic health.

Development of safe targeted therapies for idiopathic intracranial hypertension requires a thorough understanding of recent evidence discovering the pathophysiology of the condition. The aim is to provide a review of studies that inform on the underpinning mechanisms that have been associated with idiopathic intracranial hypertension.

People living with active idiopathic intracranial hypertension and obesity have been found to have with insulin resistance, hyperleptinaemia, and adverse cardiovascular outcomes. Clinically their adipose tissue is predominantly located in the truncal region and on detailed laboratory analysis the cells are primed for weight gain. There is evidence of androgen excess, altered glucocorticoid regulation and changes in pro-inflammatory cytokines. There are distinct alterations in metabolic pathways found in serum, urine and cerebrospinal fluid, that resolve following disease remission. These findings are associated with raised intracranial pressure and are likely secondary to cerebrospinal fluid hypersecretion. Idiopathic intracranial hypertension has a profile of systemic metabolic changes, endocrine dysfunction and cardiovascular risk profile distinct from that associated with obesity alone. These systemic metabolic changes are likely to contribute to dysregulation of cerebrospinal fluid dynamics, primarily hypersecretion but with a possible additional effect of reduced clearance resulting in the core feature of raised intracranial pressure.

Lipid deposition is related to agricultural animal production and human health, and elucidating its molecular regulatory mechanisms is a topic of interest and a challenge in current scientific research. Musculoskeletal embryonic nuclear protein 1 (MUSTN1) regulates growth and development, including muscle tissue; however, its role in fat deposition remains unknown. Thus, our objective was to determine this role. Our new findings were as follows: MUSTN1 was highly expressed in the fat tissue of pigs with strong adipose deposition capacity; functionally, MUSTN1 promoted the proliferation and adipogenic differentiation of porcine and mouse preadipocytes. MUSTN1 knockout mice were protected against HFD-induced obesity, hepatic steatosis, and insulin resistance; and fatty acid binding protein 3 was identified as an interacting protein of MUSTN1, which facilitated preadipocyte proliferation and differentiation by activating the phosphatidylinositol 3 kinase/AKT signaling pathways. This study reveals a positive regulator for fat development, which suggests a novel approach for studying obesity and animal genetic improvement through the modulation of MUSTN1 expression.

Obesity is a metabolic disease that is characterized by an excessive accumulation of adipose tissue (AT) and is often associated with other pathologies. AT is a lipid storage organ with endocrine functions that presents two main phenotypes: white adipose tissue (WAT) and brown adipose tissue (BAT). Preadipocytes or mature white adipocyte cells can differentiate in a middle phenotype with morpho/functional characteristics between WAT and BAT, known as brown-like or beige adipose tissue (BeAT), through the browning process. Considering the interest in stimulating the browning process in metabolic disorders and the lack of clarity, evenness, and reproducibility of the preclinical models, the detailed description of an adipocyte differentiation protocol and the "de novo" development of a beige adipocyte phenotype has been described. Furthermore, the most described stimuli in inducing the browning process, such as PPAR-γ agonists (using rosiglitazone, RGZ) and β-adrenergic stimulators (using isoproterenol, ISO), were evaluated in order to describe their involvement in the browning process and identify a reference compound for the induction of the "de novo" browning.

Immortalized murine embryonic fibroblasts (3T3-L1) cells were differentiated for up to 17 days using a differentiation medium (DM) and a maintenance medium (MM) with or without RGZ or ISO to obtain both the mature white and the beige adipocyte phenotype. The differentiation was evaluated by the Oil Red O (ORO) staining assay, citrate synthase activity, and mitochondrial uncoupling protein 1 (UCP-1) immunodetection and expression performed on different days (T0, T3, T10, and T17) after the induction of differentiation.

The results indicated that RGZ induced morphology and ORO-positive lipid deposits and increased the activity of citrate synthase enzyme and UCP-1 levels overlapping with a beige adipocyte phenotype after 17 days. ISO did not display a significant effect in these experimental conditions.

Overall, this work describes in depth the different phases of the adipocyte differentiation process by offering a detailed and reproducible "de novo" browning differentiation model. Furthermore, the efficacy of the stimulation of the PPAR-γ pathway in obtaining a beige adipocyte phenotype demonstrates that RGZ can induce the browning process and elects it as a perfect reference compound for experimental procedures in this field.

Despite accumulating evidence on central obesity and osteoporosis, the role of a body shape index (ABSI), a nonlinear index quantifying body shape via body mass index (BMI), waist circumference (WC), and height, remains controversial and underexplored. Although recent meta-analyses suggest central obesity may modulate fracture risk bidirectionally, no research has comprehensively compared ABSI with traditional adiposity metrics, such as BMI, WC, and waist-to-height ratio (WHtR), to predict site-specific changes in bone mineral density (BMD) across anatomical regions.

This study utilized National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018, involving 12,421 participants. ABSI was computed using the formula: ABSI = WC/(BMI²/³ × Height¹/²). BMD was assessed at four sites-the total femur (TF), femoral neck (FN), trochanter (TR), and intertrochanter (IN) regions-via dual-energy X-ray absorptiometry (DXA). The association between ABSI and BMD was analyzed via multiple regression models and a generalized additive model (GAM). To compare ABSI's predictive efficacy with conventional adiposity indices, regression analyses juxtaposed ABSI against BMI, WC, and WHtR in assessing correlations with site-specific BMD.

After full covariate adjustment, a significant negative association was observed between ABSI and BMD in four femoral regions (P< 0.01). Smoothed curve fitting revealed a significant nonlinear relationship and threshold effect between ABSI and BMD among middle-aged and older individuals. Additionally, an inverted J-shaped curve was observed between ABSI and BMD in all four femoral regions. Meanwhile, ABSI showed significant negative associations with BMD across all femoral sites (β = -0.27 to -0.31, p-trend< 0.000001), whereas BMI, WC, and WHtR exhibited positive correlations (WHtR showing the strongest effect: β = 0.41-0.69). This highlights ABSI's ability to detect central adiposity-related bone loss obscured by conventional obesity metrics.

ABSI's robust inverse associations with femoral BMD (β = -0.27 to -0.31), persisting across nonlinear threshold analyses, establish it as a novel biomarker of central adiposity-related skeletal fragility. Unlike conventional indices reflecting mechanical loading benefits (BMI β = 0.008-0.012; WC β = 0.003-0.005; WHtR β = 0.41-0.69), ABSI specifically captures visceral fat-driven metabolic disorder-a critical pathway for osteoporosis risk stratification in normal-weight and obese populations.

Obesity is a growing global health concern, contributing to diseases such as cancer, autoimmune disorders, and neurodegenerative conditions. Adipose tissue dysfunction, characterized by abnormal adipokine secretion and chronic inflammation, plays a key role in these conditions. Adipose-derived extracellular vesicles (ADEVs) have emerged as critical mediators in obesity-related diseases. However, the study of mature adipocyte-derived EVs (mAdipo-EVs) is limited due to the short lifespan of mature adipocytes in culture, low EV yields, and the low abundance of these EV subpopulations in the circulation. Additionally, most studies rely on rodent models, which have differences in adipose tissue biology compared to humans. To overcome these challenges, we developed a standardized approach for differentiating human preadipocytes (preAdipos) into mature differentiated adipocytes (difAdipos), which produce high-yield, human adipocyte EVs (Adipo-EVs). Using visceral adipose tissue from bariatric surgical patients, we isolated the stromal vascular fraction (SVF) and differentiated preAdipos into difAdipos. Brightfield microscopy revealed that difAdipos exhibited morphological characteristics comparable to mature adipocytes (mAdipos) directly isolated from visceral adipose tissue, confirming their structural similarity. Additionally, qPCR analysis demonstrated decreased preadipocyte markers and increased mature adipocyte markers, further validating successful differentiation. Functionally, difAdipos exhibited lipolytic activity comparable to mAdipos, supporting their functional resemblance to native adipocytes. We then isolated preAdipo-EVs and difAdipo-EVs using tangential flow filtration and characterized them using bulk and single EV analysis. DifAdipo-EVs displayed classical EV and adipocyte-specific markers, with significant differences in biomarker expression compared to preAdipo-EVs. These findings demonstrate that difAdipos serve as a reliable surrogate for mature adipocytes, offering a consistent and scalable source of adipocyte-derived EVs for studying obesity and its associated disorders. Keywords: extracellular vesicles, adipocyte, adipose, adipocyte-derived extracellular vesicles, obesity.

Excess adiposity has been associated with an increased risk of several types of cancer. The relationship between fat tissue distribution in the body and these outcomes is less well known. Using data from the UK Biobank imaging substudy, we evaluated the prospective relationship between MRI-derived measurements of adipose tissue distribution and the risk of the major site-specific cancers associated with obesity.

Between 2014 and 2023, MRI measurements on adipose tissue distribution and volume were obtained from 49,044 (52.2% women) cancer-free UK Biobank participants. Quantitative MRI data included volumes of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT), total abdominal fat/height squared (TAT/h2), and muscle fat infiltration (MFI). Cox proportional hazard models adjusted for cancer-specific risk factors were used to generate HRs and 95% confidence intervals.

Incident cancer cases of the breast (N = 179), endometrium (n = 30), colorectum (n = 145), and kidney (n = 50) were ascertained over a median follow-up of 4.5 years. In women, VAT, TAT/h2, and MFI were positively associated with a risk of postmenopausal breast cancer, and ASAT was associated with an increased risk of endometrial cancer. In men, VAT and TAT/h2 were positively associated with a risk of colorectal cancer, whereas ASAT was associated with an increased risk of kidney cancer.

The present study showed that increasing volumes of VAT, ASAT, and MFI were associated with cancers at specific organ sites, indicating a potential role for adipose tissue distribution in influencing cancer risk.

Both visceral and subcutaneous fat may have an impact on the risk of certain cancers.

Malignant melanoma, a highly malignant tumor predominantly found on the skin surface, has exhibited an alarming rise in both incidence and mortality rates annually since 2012. Despite its relatively low occurrence among skin malignancies, the mortality rate of malignant melanoma remains disproportionately high. The prognosis relies heavily on early stage detection, with a significant disparity in survival rates between stage I and stage IV patients. Studies exploring insulin resistance (IR) as a potential risk factor for malignant melanoma are scarce. The present study therefore investigated the association between the triglyceride glucose (TyG) index, an indicator of IR, and malignant melanoma incidence. Retrospective data from patients diagnosed with malignant melanoma at the First Affiliated Hospital of Nanjing Medical University (Nanjing, China) between January 2019 and January 2024 were collected. Basic information, including age, sex and body mass index, and hematological test results, such as those for fasting triglycerides and fasting blood glucose, were analyzed. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were employed to explore the association between melanoma risk and the TyG index. A total of 403 participants, including 272 patients with malignant melanomas and 131 patients with nevi, were included in the study. The melanoma group exhibited significantly higher levels of the TyG index compared with the control group (P<0.001). Univariate and multivariable logistic regression analyses revealed the TyG index as an independent risk factor for melanoma incidence (OR, 6.33; 95% CI, 3.56-11.27; P<0.001). Incidence rates of melanoma significantly increased across tertiles of the TyG index (P<0.001). The ROC curve analysis identified a clinically acceptable predictive cutoff point for the TyG index. The present study therefore provides evidence that the TyG index is a significant risk factor for the incidence of malignant melanoma. The findings underscore the potential utility of the TyG index as a biomarker for diagnosing melanoma and suggest new avenues for melanoma treatment strategies.

Metabolic reprogramming of cancer cells and the tumour microenvironment are pivotal characteristics of cancers, and studying these processes offer insights and avenues for cancer diagnostics and therapeutics. Recent advancements have underscored the impact of host systemic features, termed macroenvironment, on facilitating cancer progression. During tumorigenesis, these inherent features of the host, such as germline genetics, immune profile and the metabolic status, influence how the body responds to cancer. In parallel, as cancer grows, it induces systemic effects beyond the primary tumour site and affects the macroenvironment, for example, through inflammation, the metabolic end-stage syndrome of cachexia, and metabolic dysregulation. Therefore, understanding the intricate metabolic interplay between the tumour and the host is a growing frontier in advancing cancer diagnosis and therapy. In this Review, we explore the specific contribution of the metabolic fitness of the host to cancer initiation, progression and response to therapy. We then delineate the complex metabolic crosstalk between the tumour, the microenvironment and the host, which promotes disease progression to metastasis and cachexia. The metabolic relationships among the host, cancer pathogenesis and the consequent responsive systemic manifestations during cancer progression provide new perspectives for mechanistic cancer therapy and improved management of patients with cancer.

The prostate gland is an endocrine-sensitive organ responding to multiple stimuli. Its development and function are regulated by multiple hormones (i.e. steroids such as androgens, estrogens and glucocorticoids) but also by other key hormonal systems such as those comprised by insulin-like growth factor 1 and insulin, which are sourced by different tissues [e.g. testicles/adrenal-gland/adipose-tissue/liver/pancreas, etc.). Particularly important for the endocrine control of prostatic pathophysiology and anatomy are hormones produced and/or secreted by different cell types of the pituitary gland [growth-hormone, luteinizing-hormone, follicle-stimulating hormone, and prolactin, oxytocin, arginine-vasopressin and melanocyte-stimulating hormone], which affect prostate gland function either directly or indirectly under physiological and pathophysiological conditions [e.g. metabolic dysregulation (e.g. obesity), and prostate transformations (e.g. prostate cancer)]. This review summarizes the impact of all pituitary hormone types on prostate gland under these diverse conditions including in vivo and in vitro studies.

Sarcopenia is defined by a reduction in both muscle strength and mass. Sarcopenia may be an inevitable component of the aging process, but it may also be accelerated by comorbidities and metabolic derangements. The underlying mechanisms contributing to these pathological changes remain poorly understood. We propose that chronic inflammation-mediated networks and metabolic defects that exacerbate muscle dysfunction are critical factors in sarcopenia and related diseases. Consequently, utilizing specialized pro-resolving mediators (SPMs) that function through specific G-protein coupled receptors (GPCRs) may offer effective therapeutic options for these disorders. However, challenges such as a limited understanding of SPM/receptor signaling pathways, rapid inactivation of SPMs, and the complexities of SPM synthesis impede their practical application. In this context, stable small-molecule SPM mimetics and receptor agonists present promising alternatives. Moreover, the aged adipose-skeletal axis may contribute to this process. Activating non-SPM GPCRs on adipocytes, immune cells, and muscle cells under conditions of systemic, chronic, low-grade inflammation (SCLGI) could help alleviate inflammation and metabolic dysfunction. Recent preclinical studies indicate that both SPM GPCRs and non-SPM GPCRs can mitigate symptoms of aging-related diseases such as obesity and diabetes, which are driven by chronic inflammation and metabolic disturbances. These findings suggest that targeting these receptors could provide a novel strategy for addressing various chronic inflammatory conditions, including sarcopenia.

Chronic stress in daily life is a well-known trigger for various health issues. Despite advancements in obesity research, the mechanisms governing lipid metabolism in adipose tissue during cachexia remain poorly understood.

A chronic restraint stress (CRS) model was used to induce significant physiological and psychological stress in mice. Mice were subjected to 6 h of restraint daily in 50 mL plastic tubes for seven consecutive days. A fasting control group was included for comparison. Post-stress assessments included behavioural tests, glucose and insulin tolerance tests and indirect calorimetry. Blood and adipose tissue samples were collected for mRNA and protein analyses.

CRS induced significant psychological and physiological changes in mice, including depression-like behaviours, weight loss and reduced insulin sensitivity. Notably, CRS caused extensive adipose tissue remodelling. White adipose tissue (WAT) underwent significant 'browning' accompanied by an increase in the expression of thermogenic proteins. This counteracted the stress-induced 'whitening' of brown adipose tissue (BAT), which exhibited impaired thermogenesis and functionality, thereby maintaining energy balance systematically. The glucocorticoid receptor (GR) plays a crucial role in lipid metabolism regulation during these changes. GR expression levels were inversely correlated in BAT and WAT, but aligned with the expression patterns of thermogenic proteins across adipose tissues. These findings suggest that under chronic metabolic stress, GR mediates tissue-specific responses in adipose tissues, driving functional and phenotypic transitions in BAT and WAT to maintain energy homeostasis.

This study provides novel insights into the contrasting thermogenic phenotypes of BAT and WAT under emaciation and highlights the critical role of GRs in adipose tissue remodelling during CRS and its potential as a therapeutic target. Addressing GR-mediated changes in adipose tissues may help alleviate BAT dysfunction in cachexia and promote WAT browning, enhancing metabolic stress resistance.

This study, which involved 868 patients, focused on size-dependent features (body size, pinna formation, brachycephaly, overweight) and their associations with the occurrence of canine Otitis externa. Breed, sex, and neuter status were also included. Canine patients diagnosed with Otitis externa presented between 1 January 2019 and 31 July 2022 in a referral small animal hospital were included, while dogs with matching categories presented at the Unit for Reproductive Medicine in the same time period functioned as a randomized control group. Statistical analyses included Pearson-Chi2 test, Fisher's exact test, and Bonferroni correction. p-values of <0.05 were considered statistically significant. Rhodesian Ridgebacks, non-brachycephalic breeds, intact female dogs, dogs with semi-erect ears, and large-sized breeds had a significantly reduced risk of developing Otitis externa. Conversely, Pugs, French Bulldogs, Cocker Spaniels, medium-sized breeds, dogs with erect ears, brachycephalic breeds, neutered female, and neutered male patients were more frequently diagnosed with Otitis externa. The study concluded that large breed dogs showed a reduced risk of developing Otitis externa in our data set as well as meso- and doliocephalic breeds and dogs with semi-erect pinna formation. Particularly, the Rhodesian Ridgeback and intact female dogs showed a significantly low risk of suffering from Otitis in the current study.

The weight-to-waist index (WWI) serves as an innovative metric specifically designed to assess central obesity. However, the relationship between WWI and the prevalence of post-stroke depression (PSD) remains inadequately explored in the literature.

To elucidate the relationship between WWI and PSD.

Data from the National Health and Nutrition Examination Survey 2005 to 2018 were analyzed. Multivariable logistic regression models and propensity score matching were utilized to investigate the association between WWI and PSD, with adjustments for potential confounders. The restricted cubic spline statistical method was applied to explore non-linear associations.

Participants with elevated WWI values had a significantly greater risk of developing PSD. Specifically, individuals in the higher WWI range exhibited more than twice the likelihood of developing PSD compared to those with lower WWI values (odds ratio = 2.21, 95% confidence interval: 1.84-2.66, P < 0.0001). After propensity score matching, the risk of PSD remained significantly elevated (odds ratio = 1.43, 95%confidence interval: 1.09-1.88, P = 0.01). Tertile analysis revealed that participants in the highest WWI tertile faced a significantly higher risk of PSD compared to those in the lowest tertile. Restricted cubic spline analysis further revealed a non-linear association, with the risk of PSD plateauing at higher WWI values.

There is a significant association between elevated WWI and increased risk of PSD. Thus, regular depression screening should be implemented in stroke patients with elevated WWI to enhance patient outcomes.

Childhood obesity continues to be a critical public health concern with far-reaching implications for well-being.

This study aimed to investigate the association between metabolites in plasma and feces and indicators including body mass index (BMI), BMI for age Z score (BMIZ), and body fat distribution among children aged 6 to 9 years in China.

This cross-sectional study enrolled 424 healthy children, including 186 girls and 238 boys. Dual-energy X-ray absorptiometry was used to determine the body fat content and regional fat distribution. Plasma and fecal metabolites were analyzed using targeted metabolomic technologies.

A total of 200 plasma metabolites and 212 fecal metabolites were accurately quantified via ultra-performance liquid chromatography coupled with tandem mass spectrometry. By using orthogonal projections to latent structures discriminant analysis and random forest model, we discovered that 9 plasma metabolites and 11 fecal metabolites were associated with different weight statuses. After adjusting for potential covariates and false discovery rate correction, multiple linear regression analyses revealed that plasma metabolites (fumaric acid, glycine, l-glutamine, methylmalonic acid, and succinic acid) and fecal metabolites (protocatechuic acid) were negatively associated (β -1.373 to -.016, pFDR < 0.001-0.031; β -1.008 to -.071, pFDR 0.005-0.033), while plasma metabolites (isovaleric acid, isovalerylcarnitine, l-glutamic acid, and pyroglutamic acid) and fecal metabolites (3-aminoisobutanoic acid, butyric acid, N-acetylneuraminic acid, octanoylcarnitine, oleoylcarnitine, palmitoylcarnitine, stearoylcarnitine, taurochenodesoxycholic acid, and taurodeoxycholic acid) exhibited positive associations with BMI, BMIZ, and body fat distribution (β .023-2.396, pFDR < 0.001; β .014-1.736, pFDR < 0.001-0.049).

Plasma and fecal metabolites such as glutamine may serve as potential therapeutic targets for the development of obesity.

Obesity has recently become the most prevalent diet-related disease worldwide. This study aimed to investigate the effects of aerobic exercise, stevia, and garlic extract on leptin and ghrelin receptor mRNA, as well as the interactions between insulin and glucose in relation to these genes.

A total of 50 male Wistar rats were split into two groups: one group was fed regular rodent food, while the other was fed a high-fat diet for 12 weeks to induce obesity. The obese rats were then divided into six groups of five (N = 5) based on Lee's index: an obese control group (OC), obese treated with garlic, stevia (OGS), obese aerobic exercise (OE), obese garlic and aerobic exercise (OGE), Obese stevia and aerobic exercise (OSE), and a Normal weight group (NC). The exercise groups participated in a gradually increasing aerobic walking program, whereas the stevia and garlic groups received daily oral doses of their respective extracts. The expression of leptin and ghrelin receptor genes in the hypothalamus was measured using real-time PCR, and insulin resistance was calculated using the HOMA/IR formula. Statistical analysis was conducted using ANOVA, with a significance level set at P < 0.05.

The obese (O) rats experienced a significant increase in body weight compared with the control (C) rats (p = 0.013), whereas the treated rats showed no significant changes in weight. Leptin receptor mRNA levels were significantly lower in O rats than in C rats (p = 0.00), but increased significantly in the OS (p = 0.000) and OSE (p = 0.034) groups compared with obese rats. Ghrelin receptor mRNA levels were significantly higher in the O group than in the C group (p = 0.035), but decreased in all treatment groups, with the OE (p = 0.001), OGE (p = 0.001), and OSE (p = 0.004) groups showing the greatest reductions. Insulin resistance increased slightly in the O group compared with the C group (p = 0.112), but was lowest in the OS group among all groups (p = 0.018).

Stevia significantly improved leptin and ghrelin receptor mRNA expression, glucose levels, and insulin resistance in obese rats, showing its potential as an effective dietary intervention for managing obesity.

Sex-based differences have been observed in the incidence and prognosis of various cancers, as well as in the response to immune check point inhibitors (ICIs). These disparities are partially attributed to sex-based differences in the molecular characteristics of the anticancer immune response, which are largely influenced by sex hormones. Here, we provide a comprehensive overview on how sex hormones affect innate and adaptive immunity and contribute to shaping the features of tumor immune microenvironment and response to anticancer immunotherapy. We also discuss the promising potential and challenges of combining sex hormone manipulation with anticancer immunotherapy as new therapeutic strategy. We surmise that a sex-based perspective should be part of precision medicine approaches, and sex hormones manipulation provides opportunities for innovative immune therapeutic approaches.

Testosterone, estradiol, and dihydrotestosterone share common ligand binding sites on sex hormone binding globulin and albumin. It is unknown whether and how changes in testosterone, dihydrotestosterone, and estradiol concentrations during testosterone replacement therapy affect free testosterone fraction.

To determine the effect of changes in testosterone, dihydrotestosterone, and estradiol concentrations on free testosterone fraction during testosterone replacement therapy of men with hypogonadism.

Using data from the Testosterone Trials, we assessed the association of changes in total testosterone, estradiol, and dihydrotestosterone concentrations over 12 months of testosterone replacement therapy with changes in free testosterone fraction, measured using equilibrium dialysis. We used random forests to evaluate the associations of predicted mean changes in free testosterone fraction with changes in circulating concentrations of each hormone at low, mean, or high change in the other two hormones.

Testosterone replacement therapy not only increased total testosterone, dihydrotestosterone, estradiol, and free testosterone concentrations, but also the percent free testosterone, even though sex hormone binding globulin levels did not change. The predicted changes in free testosterone fraction during testosterone replacement therapy exhibited a non-linear relationship with changes in each of total testosterone, dihydrotestosterone, and estradiol concentrations. Greater increases in testosterone, dihydrotestosterone, and estradiol levels during testosterone replacement therapy were each associated with higher model-predicted percent free testosterone. Substantially smaller changes in molar concentrations of estradiol and dihydrotestosterone had a greater effect on percent free testosterone than those in testosterone.

During testosterone replacement therapy of men with hypogonadism, changes in testosterone, dihydrotestosterone, and estradiol concentrations each altered percent free testosterone non-linearly. Small changes in estradiol concentrations exerted much larger effect on the free testosterone fraction than testosterone and dihydrotestosterone, suggesting complex interactions of the three hormones with the binding proteins. Assessment of changes in free testosterone during testosterone replacement therapy should include consideration of changes in all three hormones.

The differentiation and lipid metabolism of preadipocytes are crucial processes in IMF deposition. Studies have demonstrated that SIRT4 plays essential roles in energy metabolism and redox homeostasis, with its expression being coordinately regulated by multiple transcription factors associated with energy and lipid metabolism. In this study, the findings of multiple omics analysis reveal that SIRT4 significantly up-regulates the expression of genes involved in adipogenesis and enhances the differentiation and lipid deposition of bovine preadipocytes. Furthermore, SIRT4 profoundly influences the expression pattern of metabolites by increasing the abundance of substances involved in lipid synthesis while decreasing those that promote lipid oxidative decomposition. Additionally, SIRT4 broadly up-regulates the expression levels of various lipid classes, including glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids. These findings not only provide a theoretical basis for molecular breeding and genetic improvement in beef cattle, but also offer potential therapeutic approaches for energy homeostasis disorders and obesity.

Exposure to arsenic (As) and its metabolites can affect normal growth in children, but the combine effects at simultaneous low-level exposures, remain uncertain. Hence, this study aims to analyze how the combined effects of As and its metabolites can impact growth indicators in 1,792 US children aged 6-12 years, from the NHANES.

Levels of arsenic species in urine were measured using HPLC coupled with ICP-DRC-MS during the 2007-2020 NHANES cycles. The sum of iAs ([AsIII + AsV]), MMA, and DMA was used as a biomarker of internal iAs exposure (∑As), and methylation efficiency was assessed using the primary and secondary methylation indices (PMI, SMI). Linear regression and BKMR models were applied to identify adverse effects, nonlinear associations, interactions, and combined effects.

Median concentrations of MMA, DMA, iAs, and ∑As were 0.56 μg/L, 4.07 μg/L, 1.33 μg/L, and 6.40 μg/L, respectively. In the linear regression analyses, higher urinary concentrations of MMA were associated with reductions in several growth indicators. Specifically, each interquartile range (IQR) increase in MMA concentration was linked to decreases of -0.18 (95 % CI: -0.29, -0.06) in Body Mass Index (BMI) Z-score, -0.18 (95 % CI: -0.29, -0.06) in Weight Z-score, and -0.01 (95 % CI: -0.02, -0.01) in Waist circumference/Height ratio. Additionally, higher DMA concentrations were negatively associated with Height Z-score, with a reduction of -0.08 (95 % CI: -0.15, -0.01). In the BKMR analysis, DMA consistently emerged as the dominant contributor across multiple outcomes, showing the highest Posterior Inclusion Probabilities (PIPs) for indicators such as BMI Z-score and Waist circumference/Height ratio. While MMA exhibited notable PIPs in certain models, its influence was generally weaker than that of DMA.

Childhood exposure to a mixture of arsenic species, even at low levels, appears to influence growth indicators and adversely affect physical development in children enrolled in NHANES.

Ovariectomized (OVX) mice serve as a key model for studying postmenopausal metabolic changes, particularly obesity, as they mimic the hormonal state of postmenopausal women. However, our understanding remains limited regarding how hormonal and dietary factors affect different adipose tissues. Furthermore, precise documentation of experimental procedures and their effects on specific adipose tissue depots is essential for reproducible translational research. This study investigated depot-specific adiposity development in OVX mice fed a high-fat diet (HFD), focusing on how reduced estrogen levels and dietary intervention affect distinct fat depots. We composed subcutaneous and visceral white adipose tissue (WAT) depots from sham-operated (Sham) and OVX female C57BL/6JJcl mice on a regular diet (RD) and high-fat diet (HFD) for 20 weeks. OVX mice on HFD gained significantly more weight than Sham controls. Adiposity increased in abdominal subcutaneous WAT (sWAT) and perirenal WAT (prWAT) of OVX mice, but not in mesenteric WAT (mWAT). Analysis of adipose tissue morphology revealed that OVX mice exhibited enlarged adipocyte cross-sectional areas under low estrogen (E2) conditions, suggesting enhanced adipogenesis in an estrogen-deficient state. These findings suggest that low estrogen condition accelerated adiposity, in a tissue site-dependent manner.

Most patients with lung cancer experience cancer cachexia (CC), a syndrome of skeletal muscle and adipose tissue wasting. Knowledge of body composition changes in patients is limited, however, because most studies have been cross-sectional, comparing patients with noncancer controls or patients with and without CC. Few studies, in contrast, have evaluated body composition in patients with lung cancer over time. This review examines our current understanding of longitudinal body composition changes in patients with lung cancer and identifies modifying factors contributing to variation in muscle and adipose tissue wasting, focusing on biological sex. We identified 32 studies conducting longitudinal measurements of body composition by computed tomography, bioelectrical impedance, dual X-ray absorptiometry, or total body nitrogen, with a total of n = 3,951 patients (35% female). All studies evaluated changes following diagnosis while patients were receiving treatment. Most studies reporting muscle-specific outcomes show decreased skeletal muscle mass, with more pronounced muscle wasting in males and male-enriched populations. In a small number of studies reporting muscle density, the majority show increased myosteatosis. Adiposity changes are less frequently reported, although wasting appears more prevalent in late-stage disease. Further studies are needed to define adipose changes along the lung cancer continuum. Our review emphasizes the need for balanced recruitment based on biological sex and sex-based analyses. In addition, consensus reporting of relevant patient data and outcomes in future studies will allow for meta-analysis and assist in the development of effective treatments for lung CC.

Treatment decisions are challenging in older adults with solid tumors. Geriatric 8 (G8)-screening and comprehensive geriatric assessment (CGA) are important but additional methods are needed. We examined the association of computed tomography (CT)-derived high visceral adipose tissue index (VATI) with or without low skeletal muscle index (SMI) on three-month and overall survival (OS).

Vulnerability was evaluated with G8 in patients ≥75 years referred for systemic anticancer treatment. Vulnerable/frail patients (G8 ≤ 14) received CGA and were included. VATI and SMI were retrospectively measured from CT scans. We examined associations between high VATI with or without low SMI and three-month and OS with Cox regression models and Kaplan-Meier estimation.

Seventy-nine patients with median age of 80 (range 75-91) years were evaluated. In the palliative-intent group (n = 58), three-month OS rates were 88 % and 58 % in the normal and high VATI groups, respectively (hazard ratio 4.3; 95 % confidence interval 1.3-14), and 88 % vs. 47 % in group without and with 'high VATI+low SMI', respectively (5.5; 1.9-17). The median OS was 12.7 vs. 9.5 months in normal VATI/SMI and 'high VATI+low SMI' (1.9; 1.1-3.2), respectively. In Cox multivariable models with established predictive factors (ECOG PS, Clinical Frailty Scale, and sex), only high VATI (4.9; 1.0-24) or 'high VATI+low SMI' (8.9; 1.7-46) remained significant predictors of three-month OS.

High VATI with or without low SMI were associated with impaired three-month OS in the palliative-intent group and with OS in the whole cohort independently of oncologic and geriatric functional status measures; thus, they may aid in treatment decision-making.

Lipedema is considered an inflammation-related disease, and low-carbohydrate ketogenic diets may help reduce inflammation. However, no randomized controlled trials have investigated the effect of a low-carbohydrate ketogenic diet on inflammatory markers in females with lipedema.

To compare changes in inflammatory and fibrosis-associated markers after a low-energy low-carbohydrate diet (LCD) compared with a low-fat diet in females with lipedema, and to explore potential associations between changes in pain and changes in inflammatory and fibrosis-associated markers.

Females with lipedema and obesity were randomly assigned to either an LCD or low-fat diet (both 1200 kcal/d) for 8 weeks. Body composition [fat mass (FM) and fat-free mass] and the plasma concentrations of high-sensitivity C-reactive protein (hsCRP), cytokines, and fibrosis-associated markers were measured pre- and postintervention.

A total of 70 females were included (35/group) (mean age: 47.3 ± 10.9 y, BMI: 36.9 ± 4.9 kg/m2). Both groups lost weight and FM (kg and %), with a greater reduction in the LCD group. A reduction in macrophage inflammatory protein-1ß, tumor necrosis factor-α, and hsCRP was seen in the LCD group only, despite no significant differences between groups. No associations were found between changes in pain and changes in cytokines and fibrosis-associated markers.

Changes in cytokines and fibrosis-associated markers did not differ between low-energy LCD and low-fat diets in females with lipedema, despite a beneficial profile in the LCD group. Inflammation does not seem to be involved in pain reduction following LCD in this patient group.

This trial was registered at clinicaltrials.gov as NCT04632810.