Pathophysiology Of Obesity Research Articles

Fatty Bacteria in the Intestine and Collagen Bacteria (Dominio: Bacteria Woese, Kandler & Wheelis 1990): Therapies and Biotechnology

Recent evidence has suggested that the intestinal microbiota is involved in energy regulation and the inflammatory process, an environmental factor related to the pathophysiology of obesity. The microbiota contains a variety of living microorganisms that colonize the intestine, and its development occurs throughout the life cycle from birth to adulthood. Collagen is one of these ingredients with functional characteristics. It is a protein of animal origin, whose function in the body is to contribute to the structural integrity of the tissues in which it is present. However, with the onset of adulthood, collagen deficiency begins to be noticed, as the body reduces its production, making its supplementation necessary. This review aims to study fatty bacteria in the intestine and collagen bacteria. Data were collected using a quantitative and descriptive approach, through books and the following databases: SciVerse Scopus, Scientific Electronic Library Online (SciELO), the Academic Search Tool (Scholar Google), Academia.edu., Researchgate, Library of Medicine and National Institute of Health (USA), (PubMed) and Scientific, Latin American Literature in Health Sciences (LILACS). The search was developed using the subject descriptor, mosquito, diseases, filaria, hosts, transmission, diagnosis, and treatment referred to in periodicals, through a literature review. In the initial search, the titles and abstracts of the articles were considered for the broad selection of likely works of interest, with the abstracts being highlighted.

Effect of sarcopenic obesity on treatment results in patients with malignant tumors of the gastrointestinal tract: systematic review

Background. Tumors of the gastrointestinal (GI) tract are characterized by high morbidity and poor prognosis. Over the past decade, sarcopenia (skeletal muscle depletion), myosteatosis, sarcopenic obesity were all shown to have negative prognostic effect in patients with various GI malignancies. However, the role of sarcopenic obesity (SO) in patients with GI tumors remains controversial. We have summarized clinical trial data on the effect of SO on treatment results in patients with malignant GI tumors who underwent surgical and/or drug antitumor treatment.Materials and methods. Thisstudy was conducted in comliance with the Preferred Reporting Itemsfor Systematic Review and Meta-Analyses (PRISMA) guidelines. PubMed and Cochrane Library databases were searched for relevant original studies published between January 2009 and December 2022 reporting postoperative complication rate and mortality, long-term survival and chemotherapy toxicity in SO patients with GI cancers.Results. Twenty four studies with 9,601 patients were included. The percentage of SO patients ranged from 2.6 to 51 %. Due to significant heterogeneity of SO determination methods and varying threshold values, the association between SO and outcomes of interest was inconsistent. SO was significantly associated with development of major postoperative complications in six studies. In contrast, three studies did not show any effect of SO on postoperative complications. Only two studies demonstrated that the mortality rate was significantly higher among patients with SO compared to those without SO. Four studies using multivariate analysis showed statistically significant effect of SO on long-term survival, one study – on disease-free survival. However, three trials contradicted this finding and reported that SO was not a negative prognostic factor of long-term survival in GI cancer patients. Three studies investigating SO effect on the outcomes of drug antitumor treatment showed negative effect of SO on chemotherapy toxicity.Conclusion. There is considerable heterogeneity in methods used to define SO in the literature, and current data is limited. Standardized terminology and deeper understanding of sarcopenic obesity pathophysiology is needed to further understand the effect of obesity and sarcopenia on clinical trajectory of patients with GI cancer.

Epigenetics of childhood obesity.

Childhood obesity has become a global pandemic and is one of the strongest risk factors for cardiovascular disease later in life. The correlation of epigenetic marks with obesity and related traits is being elucidated. This review summarizes the latest research and its challenges in the study of epigenetics of (childhood) obesity. Epigenome-wide association studies helped to identify novel targets and methylation sites that are important in the pathophysiology of obesity. In the future, such sites will become essential for developing methylation risk scores (MRS) for metabolic and cardiovascular diseases. Although MRS are very promising for predicting the individual risk for obesity, the implementation of MRS is challenging and has not been introduced into clinical practice so far. Future research will undoubtedly discover numerous methylation sites that may be involved in the development of obesity and its comorbidities, especially at a young age. This will contribute to a better understanding of the complex etiology of human obesity. From a clinical perspective, the overarching aim is to generate MRS that are robust for reliable and accurate prediction of obesity and its comorbidities.

The association between circulating irisin, osteocalcin and FGF21 levels with anthropometric characteristics and blood lipid profile in young obese male subjects.

Myokines secreted from skeletal muscle such as irisin, osteokines secreted from bone such as osteocalcin, and hepatokines secreted from the liver such as fibroblast growth factor 21 (FGF21) play a role in the regulation of metabolic homeostasis. However, the changes that occur in obesity and the interaction between them have not been fully explained. Therefore, this study aimed to compare irisin, osteocalcin and FGF21 levels in young obese males against individuals with normal body weight and to reveal the possible relationship between them and with anthropometric measurements and blood lipid profile. This single-center study included 28 Turkish young males aged 20-29 years: 14 obese participants with a body mass index (BMI) between 30.0-34.9 and 14 healthy controls with a BMI between 18.5-24.9. Anthropometric, and body composition parameters, blood lipid profile, and irisin, osteocalcin and FGF21 levels of groups were measured. Correlation analyses were performed between irisin, osteocalcin, and FGF21 and other measured parameters. Circulating irisin, osteocalcin and FGF21 levels were significantly higher in the obese group than in the control group (p < 0.05). Correlation analysis showed that irisin was positively correlated with total cholesterol, triglycerides and low density lipoprotein-cholesterol (LDL-C) and FGF21 was positively correlated with total cholesterol and LDL-C (p < 0.05). Positive correlation between irisin and osteocalcin, FGF21 and osteocalcin and FGF21 and irisin was observed (p < 0.05). Irisin, osteocalcin, and FGF21 have a potential role in the pathophysiology of obesity and related metabolic diseases due to their interactions.

Aerobic exercise improves energy and glucose homeostasis through hypothalamic Mitofusion 2-rescued endoplasmic reticulum stress in diet-induced obese mice.

Hypothalamic endoplasmic reticulum stress (ERS) and mitochondrial dysfunction are two important mechanisms involved in the pathophysiology of obesity, which can be reversed by aerobic exercise to improve organ function. Mitofusion 2 (Mfn2), a mitochondrial membrane protein, affects both mitochondrial dynamics and ER morphology. This study explored the contribution of hypothalamic Mfn2 to exercise-induced improvements in energy homeostasis and peripheral metabolism and the underlying mechanisms involved. We determined the effects of aerobic exercise on energy metabolism and the expression of Mfn2 and α-MSH in the hypothalamus of diet-induced obesity (DIO) model mice. In addition, hypothalamic ER signalling and insulin signalling in both the hypothalamus and the liver were evaluated following 4 weeks of aerobic exercise. By using an adenovirus carrying shRNA-Mfn2, we further explored the effects of hypothalamic Mfn2 on exercise-induced improvements in energy metabolism, ER signalling and insulin signalling. Energy metabolism was obviously improved following 4 weeks of aerobic exercise in DIO model mice. However, after hypothalamic Mfn2 knockdown, the effects of exercise on food intake and peripheral metabolism were significantly suppressed. Hypothalamic ER signalling was attenuated significantly, whereas both hypothalamic and hepatic insulin signalling were obviously activated following aerobic exercise. Nevertheless, exercise-induced improvements in ER signalling and insulin signalling were attenuated significantly after Mfn2 knockdown. These data indicate that aerobic exercise improves whole-body metabolism in DIO mice, probably via increased hypothalamic Mfn2, which could be further mediated by attenuated HFD-induced ER stress in the hypothalamus.

The Evolving Role of Neutrophils and Neutrophil Extracellular Traps (NETs) in Obesity and Related Diseases: Recent Insights and Advances.

Obesity is a chronic, multifactorial disease characterized by persistent low-grade tissue and systemic inflammation. Fat accumulation in adipose tissue (AT) leads to stress and dysfunctional adipocytes, along with the infiltration of immune cells, which initiates and sustains inflammation. Neutrophils are the first immune cells to infiltrate AT during high-fat diet (HFD)-induced obesity. Emerging evidence suggests that the formation and release of neutrophil extracellular traps (NETs) play a significant role in the progression of obesity and related diseases. Additionally, obesity is associated with an imbalance in gut microbiota and increased intestinal barrier permeability, resulting in the translocation of live bacteria, bacterial deoxyribonucleic acid (DNA), lipopolysaccharides (LPS), and pro-inflammatory cytokines into the bloodstream and AT, thereby contributing to metabolic inflammation. Recent research has also shown that short-chain fatty acids (SCFAs), produced by gut microbiota, can influence various functions of neutrophils, including their activation, migration, and the generation of inflammatory mediators. This review comprehensively summarizes recent advancements in understanding the role of neutrophils and NET formation in the pathophysiology of obesity and related disorders while also focusing on updated potential therapeutic approaches targeting NETs based on studies conducted in humans and animal models.

FcRn-dependent IgG accumulation in adipose tissue unmasks obesity pathophysiology.

Immunoglobulin G (IgG) is traditionally recognized as a plasma protein that neutralizes antigens for immune defense. However, our research demonstrates that IgG predominantly accumulates in adipose tissue during obesity development, triggering insulin resistance and macrophage infiltration. This accumulation is governed by neonatal Fc receptor (FcRn)-dependent recycling, orchestrated in adipose progenitor cells and macrophages during the early and late stages of diet-induced obesity (DIO), respectively. Targeting FcRn abolished IgG accumulation and rectified insulin resistance and metabolic degeneration in DIO. By integrating artificial intelligence (AI) modeling with invivo and invitro experimental models, we unexpectedly uncovered an interaction between IgG's Fc-CH3 domain and the insulin receptor's ectodomain. This interaction hinders insulin binding, consequently obstructing insulin signaling and adipocyte functions. These findings unveil adipose IgG accumulation as a driving force in obesity pathophysiology, providing a novel therapeutic strategy to tackle metabolic dysfunctions.

MetAP2 as a Therapeutic Target for Obesity and Type 2 Diabetes: Structural Insights, Mechanistic Roles, and Inhibitor Development.

Type 2 Diabetes Mellitus (T2DM) and obesity are globally prevalent metabolic disorders characterized by insulin resistance, impaired glucose metabolism, and excessive adiposity. Methionine aminopeptidase 2 (MetAP2), an intracellular metalloprotease, has emerged as a promising therapeutic target due to its critical role in regulating lipid metabolism, energy balance, and protein synthesis. This review provides a comprehensive analysis of MetAP2, including its structural characteristics, catalytic mechanism, and functional roles in the pathophysiology of T2DM and obesity. The unique architecture of MetAP2's active site and its interactions with substrates are examined to elucidate its enzymatic function. The review also explores the development of MetAP2 inhibitors, focusing on their mechanisms of action, preclinical and clinical findings, and therapeutic potential. Special emphasis is placed on docking studies to analyze the binding interactions of six key inhibitors (fumagillin, TNP-470, beloranib, ZGN-1061, indazole, and pyrazolo[4,3-b]indole) with MetAP2, revealing their structural determinants for efficacy and specificity. These findings underscore the potential of MetAP2 as a therapeutic target and provide valuable insights for the rational design of next-generation inhibitors to address obesity and T2DM.

Unveiling the endocrine connections of NAFLD: evidence from a comprehensive mendelian randomization study.

NAFLD is gaining recognition as a complex, multifactorial condition with suspected associations with endocrine disorders. This investigation employed MR analysis to explore the potential causality linking NAFLD to a spectrum of endocrine diseases, encompassing T1D, T2D, obesity, graves' disease, and acromegaly. Our methodology leveraged a stringent IV selection process, adhering to the STROBE-MR guidelines. The MR analysis was conducted utilizing three distinct methods: IVW, WM, and MR-Egger. The IVW method was prioritized as the primary analytical approach. We conducted MR analyses to analyze the causal relationship between NAFLD and metabolic disorders. We also examined 1400 metabolites implicated in NAFLD. Metabolic pathway analysis was performed using the MetaboAnalyst database. The findings indicated that T2D (OR = 1.211, 95%CI: 0.836-1.585) and obesity (OR = 1.245, 95%CI: 0.816-1.674) are associated with an increased risk of NAFLD development. Further exploration into the the 1400 metabolites revealed that cys-gly and diacetylornithine are predictive of NAFLD, T2D, and obesity, whereas isovalerylcarnitine exhibited an inverse association, potentially inhibiting disease development. Metabolic pathways involving alanine, aspartate, and glutamate metabolism were identified as pivotal regulators in the pathophysiology of NAFLD, T2D, and obesity. The present study generated innovative viewpoints on the etiology of NAFLD. Our findings underscore the significant role of T2D and obesity in NAFLD pathogenesis through metabolic pathways, presenting opportunities for targeted therapeutic strategies and warranting further investigation. The online version contains supplementary material available at 10.1007/s13534-024-00442-8.

Sex-Specific Differences in Lipid Metabolism in Obesity: Implications for Cardiometabolic Risk

Sex-specific differences in lipid metabolism play a critical role in the pathophysiology of obesity and its related cardiometabolic risks. Men and women exhibit distinct patterns of fat distribution, lipid handling, and hormonal regulation, contributing to varying susceptibilities to conditions like dyslipidemia, insulin resistance, cardiovascular diseases (CVD), and metabolic syndrome. In women, subcutaneous fat deposition is more prominent, whereas men tend to accumulate visceral fat, which is associated with greater cardiometabolic risk. These differences are influenced by sex hormones, particularly estrogen, which has protective effects on lipid profiles in premenopausal women, but diminishes post-menopause, increasing CVD risk. Furthermore, genetic, epigenetic, and lifestyle factors modulate these sex-specific lipid metabolic processes. Understanding these differences is crucial for developing targeted therapeutic strategies aimed at reducing the burden of obesity-associated cardiometabolic disorders. This review explores the mechanisms underlying sex differences in lipid metabolism, their implications for cardiometabolic risk, and potential interventions to address sex-specific metabolic dysfunction in obesity. Keywords: Sex differences, lipid metabolism, obesity, cardiometabolic risk, estrogen, visceral fat, metabolic syndrome

Interactions between the gut microbiome and DNA methylation patterns in blood and visceral adipose tissue in subjects with different metabolic characteristics

BackgroundThe gut microbiome has been reported to induce epigenetic modifications in the host, which may be involved in the pathophysiology of metabolic diseases.ObjectiveTo evaluate the potential interactions between the gut microbiome and DNA methylome in subjects with different metabolic characteristics.MethodsSixty-four participants with different metabolic characteristics (i.e., participants without obesity -healthy controls-, and participants with obesity and normal insulin sensitivity/insulin resistance/ type 2 diabetes-T2DM-) were included in this study. A machine learning approach was performed in order to identify distinctive patterns in three omics (gut microbiome, blood DNA methylome, and visceral adipose tissue-VAT- DNA methylome) according to the different study groups.ResultsRobust distinctive distribution patterns of the three different omics were found between healthy controls and patients with obesity; participants with and without T2DM, and patients with obesity with and without insulin resistance. Importantly, strong correlations between the gut microbiome (including Odoribacteriaceae and Christensenllaceae families) and both blood and VAT DNA methylome were found. Moreover, in the entire study population, three main bacterial genera (Sutterella, Collinsella and Eubacterium) were related to the epigenetic regulation of different genes involved in distinct processes related to cellular metabolism and metabolic diseases, including small ubiquitin-related modifier (SUMO) transferase activity or lipid binding.ConclusionWe show that distinctive interactions between the gut microbiome and DNA methylome may occur in subjects with different metabolic characteristics. Further research is needed to elucidate the potential role of these interactions in the pathophysiology of obesity and related comorbidities.

비만 표현형에 따른 비만 치료의 기능의학적 접근

According to recent studies, it has become evident that there is diversity in how the individuals, from a metabolic point of view, are affected by obesity. Difference in pathophysiology for each phenotype of obesity, may confer need for tailored approaches for the phenotype to maximize treatment effects. This narrative review, based on functional medicine, try to elucidate distinct feature of each phenotype of obesity and suggests a new approach which integrates body metabolism, energy balance into obesity management, in order not just to reduce body weight but also dissolve body fat which is a center of obesity pathophysiology. This approach leads to personalized treatment that work best for each obesity phenotype in reducing the risk of non-communicable diseases in clinical practice.

Gut Microbiota-microRNA Interactions and Obesity Pathophysiology: A Systematic Review of Integrated Studies.

Obesity is the fifth leading cause of death globally and its comorbidities put a high burden on societies and cause disability. In this review, we aim to summarize the interactions and crosstalk between gut microbiota and micro-RNA (miRNA) in obesity. We searched for the relevant literature through PubMed, Web of Science, Scopus, and Science Direct. The study design is registered in the international prospective register of systematic reviews (Prospero). According to the inclusion criteria, eight studies were eligible for assessment (two studies including human subjects and six studies including animal subjects). We report that the interactions of miRNA and gut microbiota in the context of obesity are diverse and in some cases tissue specific. However, the interactions mediate obesity-associated pathways including the inflammatory response, oxidative stress, insulin signaling, gut permeability, and lipogenesis. To mention the most meaningful results, the expression of adipose tissue miRNA-378a-3p/5p was associated with Bifidobacterium and Akkermansia abundance, the expression of hepatic miRNA-34a was related to the Firmicutes phylum, and the expression of miRNA-122-5p and miRNA-375 was associated with the Bacteroides genus. miRNA-microbiota-associated pathological pathways seem to provide an intricate, but promising field for future research directed toward the treatment of obesity and its comorbidities.

Obesity: Complications, Complexities and Care Considerations

Obesity is a chronic metabolic disorder that continues to increase in prevalence in the United States and the world. It is a risk factor for cardiovascular disease and multiple malignancies. The pathophysiology of obesity is extremely complicated and not entirely understood but multiple factors and mechanisms involving conscious diet patterns, food quality and availability, neurotransmitters in the brain and gut driving satiety and hunger, and patterns of physical activity play a role. There are treatment options available for obesity including surgery and medication for many patients who suffer with this disease when proper diet and physical activity do not achieve sustained remission.

Anti-Obesity Effects of Calcium Fructoborate by Inhibiting Adipogenesis and Increasing SIRT's Expression in 3T3-L1 Cells.

Obesity is a global public health problem that can lead to mortality and morbidity. Studies on the pathophysiology of obesity for effective and safe treatments are focused on the mechanisms of adipogenesis. The association between boron treatment and weight loss has been reported, but its anti-adipogenic mechanisms and effects on preadipocytes remain unclear. This study aims to investigate the effects of boron compounds boric acid (BA) and calcium fructoborate (CaFB) on adipogenesis using the most widely used in vitro 3T3-L1 cellular model. In our study, cytotoxicity, Oil Red O (ORO), gene and protein expression analyses and cellular NAD measurements of boron compounds were performed. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) transcription factors are the main regulators of adipogenesis, and boron compounds affect them at gene and protein levels by showing anti-obesity effects. This is the first study to show that CaFB has anti-obesity properties in mouse adipocytes. Sirtuins, known as the longevity genes, were also activated from boron treatment. Results of this research provide new basic knowledge and insights into the effect of boron-based compounds on obesity. It also offers potential prospects for the development of effective treatment and/or supportive treatment methods.

Body weight control via protein kinase CK2: diet-induced obesity counteracted by pharmacological targeting

BackgroundProtein kinase CK2 is a highly conserved enzyme implicated in the pathogenesis of various human illnesses including obesity. Despite compelling evidence for the involvement of this kinase in the pathophysiology of obesity, the molecular mechanisms by which CK2 might regulate fat metabolism are still poorly understood. Methods and resultsIn this study, we aimed to elucidate the role of CK2 on lipid metabolism by employing both in vitro and in vivo approaches using mouse pre-adipocytes and a mouse model of diet-induced obesity. We show that pharmacological inhibition of CK2 by CX-4945 results in premature upregulation of p27KIP1 preventing the progression of cells into mature adipocytes by arresting their development at the intermediate phase of adipogenic differentiation. Consistent with this, we show that in vivo, CK2 regulates the expression levels and ERK-mediated phosphorylation of C/EBPβ, which is one of the earliest transcription factors responsive to adipogenic stimuli. Furthermore, we demonstrate the functional implication of CK2 in the expression of late markers of adipogenesis and factors regulating lipogenesis in liver and white adipose tissue. Finally, we show that while mice subjected to high-fat diet increased their body weight, those additionally treated with CX-4945 gained considerably less weight. NMR-based body composition analysis revealed that this is linked to significant differences in body fat mass. ConclusionsTaken together, our study provides novel insights into the role of CK2 in fat metabolism in response to chronic lipid overload and confirms CK2 pharmacological targeting as a potentially powerful strategy for body weight control and/or the treatment of obesity and related metabolic disorders.

Setmelanotide: A Melanocortin-4 Receptor Agonist for the Treatment of Severe Obesity Due to Hypothalamic Dysfunction.

Obesity is a silent global pandemic. It is a condition associated with multiple risk factors and adverse outcomes that arise from the intertwined relationship between environmental factors and genetics. The genetic factors that cause phenotypic expression are variable. Monogenic obesity is a severe early-onset and rarer form of obesity, which presents with co-morbidities such as abnormal feeding behaviour. Monogenic obesity causes impaired weight regulation in the hypothalamus due to defects in the leptin-melanocortin signalling pathway. The emergence of a new therapeutic treatment, the melanocortin-4 receptor agonist setmelanotide (originally RM-493), has represented a breakthrough in the management of monogenic obesity and has raised hope in managing complex obesity. This review provides an overview of the setmelanotide trials that have taken place, as well as its mechanism of action, side effects and weight loss outcomes that led to its approval in the treatment of pro-opiomelanocortin (POMC) deficiency and proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency. It also explores setmelanotide's role in other genetic forms of obesity, such as hypothalamic obesity, Prader-Willi syndrome, Alström syndrome and other rare genetic conditions that are being investigated. This review aims to help to understand the pathophysiology of genetic obesity and aid in future treatment options for people with severe, complex genetic obesity.

Pediatric Obesity Pharmacotherapy: State of the Science, Research Gaps, and Opportunities.

Pediatric obesity is a major public health problem, affecting nearly 20% of children and adolescents living in the United States. In 2023, the American Academy of Pediatrics released its first clinical practice guideline for the evaluation and management of child and adolescent obesity and recommended integrating health behavior and lifestyle interventions with pharmacological treatment when medically indicated. However, there is a limited evidence base to guide antiobesity medication treatment decisions in clinical practice and limited data on long-term safety during this critical period of growth and development in youth. Thus, in November of 2023, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop to identify knowledge gaps and opportunities for research on the use of pharmacotherapy for obesity in children and adolescents. Leading scientific and clinical experts in obesity pathophysiology and treatment, pharmacotherapy, clinical trial design, and health equity and disparities, among others, identified gaps in clinical trial design, guidance for clinical use of medications in children and adolescents, additional treatment outcomes beyond body fat or weight, and improvement in care delivery. Adolescent patients and caregivers with lived experience of obesity and weight management were also invited to participate in a panel discussion, providing personal perspectives on living with obesity, clinical care considerations, and research needs. This article summarizes the workshop proceedings on the state of the science and identifies gaps and opportunities for future research to inform optimal and equitable medical management of children and adolescents with obesity.

Perspectives on obesity imaging: [18F]2FNQ1P a specific 5-HT6 brain PET radiotracer

BackgroundEstimates suggest that approximatively 25% of the world population will be overweight in 2025. Better understanding of the pathophysiology of obesity will help to develop future therapeutics. Serotonin subtype 6 receptors (5-HT6) have been shown to be critically involved in appetite reduction and weight loss. However, it is not known if the pathological cascade triggered by obesity modifies the density of 5-HT6 receptors in the brain.MethodsInfluence of diet-induced obesity (DIO) in Wistar rats was explored using MRI (whole-body fat) and PET ([18F]2FNQ1P as a specific 5-HT6 radiotracer). The primary goal was to monitor the 5-HT6 receptor density before and after a 10-week diet (DIO group). The secondary goal was to compare 5-HT6 receptor densities between DIO group, Wistar control diet group, Zucker rats (with genetic obesity) and Zucker lean strain rats.ResultsWistar rats fed with high-fat diet showed higher body fat gain than Wistar control diet rats on MRI. [18F]2FNQ1P PET analysis highlighted significant clusters of voxels (located in hippocampus, striatum, cingulate, temporal cortex and brainstem) with increased binding after high-fat diet (p < 0.05, FWE corrected).ConclusionThis study sheds a new light on the influence of high-fat diet on 5-HT6 receptors. This study also positions [18F]2FNQ1P PET as an innovative tool to explore neuronal consequences of obesity or eating disorder pathophysiology.

An optimized pipeline for high-throughput bulk RNA-Seq deconvolution illustrates the impact of obesity and weight loss on cell composition of human adipose tissue.

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. Here, we provide an optimized pipeline to estimate cellular composition in human abdominal subcutaneous adipose tissue (ASAT) from publicly available bulk RNA-Seq using signature profiles from our previously published full-length single nuclei (sn)RNA-Seq of the same depot. Individuals with obesity had greater proportions of macrophages and lower proportions of adipocyte sub-populations and vascular cells compared with lean individuals. Two months of diet-induced weight loss (DIWL) increased the estimated proportions of macrophages; however, two years of DIWL reduced the estimated proportions of macrophages, thereby suggesting a bi-phasic 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.