Obesity Conditions Research Articles

Effects of GLP-1 Receptor Polymorphisms on Adolescent Obesity

Obesity is becoming a concerning disease in developing countries. Like other multifactorial diseases, genetics plays a substantial role in the development of this disease. We tried to investigate genetic variations (mutation/polymorphism) of GLP-1R gene in children diagnosed with obesity and to identify their possible connections with obesity and other conditions. Genomic DNA was extracted from 162 overweight/obese patients and 100 controls. Later, full exon sequencing and association studies were carried out. Three polymorphisms and one mutation were detected in the fourth and fifth exons of the GLP-1R gene. Some variations were detected in three cases from which 1/3 had non-alcoholic fatty liver disease (NAFLD) but none showed insulin resistance (IR). There were also statistically meaningful results for ‘Odds Ratio’ among different genotypes and allele frequencies in groups with NAFLD and/or IR. In addition, there was an increase in risk for NAFLD and a decrease in risk for IR. In the homozygous group, also the prospect of IR was double declined. Patients with the A allele of this polymorphism showed a drop in risk for IR as well. GLP-1R polymorphisms could influence obesity and diabetes and thus the functional analysis of the GLP-1R polymorphisms is benevolent.

Influence of obesity on the tone of bronchial smooth muscles in rats

Background. Overweight and obesity are key factors for the occurrence of many morphofunctional disorders in organs and tissues, including bronchopulmonary system.The aim. To study the influence of metabolic disorders that occur against the background of obesity on the state of the airways tone in rats.Materials and methods. Obesity in male Wistar rats was induced using a high-fat and high-carbohydrate diet. In animals, body weight and fat mass were measured, and the heart-lung complex was extracted. In blood serum, the levels of glucose, insulin, leptin, triglycerides, and cholesterol were assessed. Bronchoalveolar lavage fluid was obtained by an open method, in which the concentration of protein, interleukin (IL) 6 and IL-10 was determined. The contractile activity of the isolated bronchial smooth muscle segments was studied using mechanographic method. The effect of acetylcholine (10–7–10–4 M), indomethacin (10–5 M), and forskolin (10–7–10–5 M) on the changes in the tone of airway smooth muscles was assessed.Results. High-fat and high-carbohydrate diet caused an increase in body weight, visceral obesity, hyperglycemia, insulin resistance, leptinemia, dyslipidemia in rats of the experimental group. In the bronchoalveolar lavage fluid of experimental animals, an increase in the content of protein and IL-6 was found, which positively correlated with the level of leptin and the fat mass. In obese rats, the contractile responses of bronchial smooth muscle segments increased in response to the effect of the cholinergic agent acetylcholine. The bronchoconstrictor effect of acetylcholine was reduced by the cyclooxygenase inhibitor indomethacin. In turn, the adenylate cyclase activator forskolin caused relaxation of the airway segments smooth muscles in rats of both groups, which was more pronounced in the experimental group.Conclusion. The obtained results indicate that the change in the reactivity of the respiratory tract can be the cause of bronchospastic conditions in obesity and of the inflammatory reaction in the respiratory system induced by obesity.

The Role of Transferrin, Iron and Some Biochemical Variables in Obese Males

The condition of obesity is a persistent ailment characterized by the atypical or excessive buildup of adipose tissue, resulting in compromised well-being and an elevated likelihood of morbidity and chronic health issues. The global incidence of individuals with obesity and overweight conditions has been on the rise for numerous decades. The goal of the study is to identify the relationship between body mass index (BMI), insulin, transferrin, iron, and lipid profile in obese males. Ninety males were recruited into the study; forty participants were assigned to the obese group were have BMI>30 kg/m2, twenty to overweight group were have BMI between 25-30 kg/m2, and another thirty to the control group were have slow BMI<25 kg/m2. The serum Transferrin, serum fasting insulin, serum iron, lipid profile and fasting glucose was evaluated in each of studied groups. The Obese group showed significant increase of the serum insulin concentration compared with the control group (16.77±7.68 vs. 11.7 ±2.79, p <0.001). As well as in transferrin and lipid profile significant change was detected. No prominent differences were detected in the three groups in iron and glucose concentration. Investigation of serum transferrin can be participated in future as iron deficiency marker in obese subject in conjugation with serum iron and serum ferritin.

Parental perception of facilitators and barriers to health among young children with down syndrome: a qualitative study.

Despite high rates of obesity and weight-related conditions observed in children with Down syndrome, little is known about how to prevent these conditions. The purpose of this study was to identify parent-perceived facilitators and barriers to health for toddlers (12-36 months old) with Down syndrome. We conducted in-depth, semi-structured interviews with the mothers of 25 toddlers with Down syndrome. All interviews were conducted using Zoom Video Technology, audio recorded and transcribed before being coded in NVivo software using a structured protocol. Thematic analysis was used to identify themes in perceived facilitators and barriers to health at the level of the child, family, and community. Data were triangulated using reflective journaling, video review of child meals, and member-checking techniques. We identified unique themes for facilitators (on the move and sound sleep) and barriers (co-occurring conditions and eating behaviors) at the level of the child. At the level of the family and community, overarching themes that were viewed as either a facilitator or barrier, depending on the context, were identified (role models matter, time is critical, the importance of place, and social support). These themes can help clinicians and researchers tailor their health promotion interventions to meet the unique needs of children with Down syndrome by using strength-based approaches and providing families with the tools to overcome barriers.

Human resident liver myeloid cells protect against metabolic stress in obesity.

Although multiple populations of macrophages have been described in the human liver, their function and turnover in patients with obesity at high risk of developing non-alcoholic fatty liver disease (NAFLD) and cirrhosis are currently unknown. Herein, we identify a specific human population of resident liver myeloid cells that protects against the metabolic impairment associated with obesity. By studying the turnover of liver myeloid cells in individuals undergoing liver transplantation, we find that liver myeloid cell turnover differs between humans and mice. Using single-cell techniques and flow cytometry, we determine that the proportion of the protective resident liver myeloid cells, denoted liver myeloid cells 2 (LM2), decreases during obesity. Functional validation approaches using human 2D and 3D cultures reveal that the presence of LM2 ameliorates the oxidative stress associated with obese conditions. Our study indicates that resident myeloid cells could be a therapeutic target to decrease the oxidative stress associated with NAFLD.

Numerical simulation of calcium dynamics dependent ATP degradation, IP3 and NADH production due to obesity in a hepatocyte cell.

Calcium (Ca[Formula: see text]) signals have a crucial role in regulating various processes of almost every cell to maintain its structure and function. Calcium dynamics has been studied in various cells including hepatocytes by many researchers, but the mechanisms of calcium signals involved in regulation and dysregulation of various processes like ATP degradation rate, IP[Formula: see text] and NADH production rate respectively in normal and obese cells are still poorly understood. In this paper, a reaction diffusion equation of calcium is employed to propose a model of calcium dynamics by coupling ATP degradation rate, IP[Formula: see text] and NADH production rate in hepatocyte cells under normal and obese conditions. The processes like source influx, buffer, endoplasmic reticulum (ER), mitochondrial calcium uniporters (MCU) and Na[Formula: see text]/Ca[Formula: see text] exchanger (NCX) have been incorporated in the model. Linear finite element method is used along spatial dimension, and Crank-Nicolson method is used along temporal dimension for numerical simulation. The results have been obtained for the normal hepatocyte cells and for cells due to obesity. The comparative study of these results reveal significant difference caused due to obesity in Ca[Formula: see text] dynamics as well as in ATP degradation rate, IP[Formula: see text] and NADH production rate.

Excess Body Weight and Physical Education: Opportunities Are at Hand

Childhood overweight and obesity concerns continue to frame much of the discussion about physical activity in schools and school-based physical education. There are multiple factors impacting childhood obesity rates. Genetics, ethnicity, guardian education level, health-care access, food costs, cultural beliefs, policy, and energy-balance inequalities have all played a role in the current state of childhood overweight and obesity. Since schools are an ideal place to interact with children and adolescents of all body compositions, multiple researchers have attempted to design, implement, and evaluate school-based physical activity interventions. Many of the interventions have produced significant results. Overweight and obesity is not physical education’s problem, but it does present an opportunity for physical education to grow as an academic discipline as new interventions and curricula are developed and disseminated. This article focused on the large-scale, school-based, physical activity interventions that needs to be designed, implemented, and evaluated using rigorous standards and policymaker and educational community support.

Postural balance and body mass index in older adults; a descriptive and associative study testing traditional risk factors.

There is a scarcity of information about how much the postural balance parameters, as the area and mean velocity of the center of pressure (CoP), can be modified by traditionally adiposity markers in older adults. To describe and associate postural balance parameters in Chilean older adults with different BMI. A second objective was to associate the area of balance with weight. In a descriptive study, Chilean older adults (mean age; 70 ± 1.0, BMI 29.0 ± 0.4 kg/m2) were categorized by a normoweight control group (CG, n = 7, BMI; 23.1 ± 0.5), overweight (OvW, n = 41, BMI; 27.6 ± 0.2), and obesity (Ob, n = 23, BMI; 34.2 ± 0.5). The subjects were evaluated on a stable/hard [HS]/soft [SS] surface, and under open [OE]/ closed [CE] eyes. Secondary outcomes were weight, height, BMI, and functional health. Univariate test and linear regression were applied. CoP mean velocity on the HS and CE, showed significant differences between CG vs. OvW groups (24.9 ± 7.4 mm/s vs. 12.1 ± 0.97 mm/s, p < 0.0001). There were significant differences in Romberg index between CG vs. OvW group (176.7 ± 16.4% vs. 132.4 ± 7.1%, p = 0.002), and between CG vs. Ob group (176.7 ± 16.4% vs. 129.4 ± 17.2%, p = 0.005). On the SS with OE, there were significant differences between CG vs. OvW groups (29.8 ± 4.8 mm/s vs. 18.6 ± 1.2 mm/s, p < 0.003), and, on the SS, with CE, between CG vs. OvW groups (41.5 ± 31.2 mm/s vs. 24.6 ± 15.2 mm/s, p = 0.015). At higher BMI such as at overweight or obesity conditions, older adults show a reduced 'CoP mean velocity' than control normoweight peers', being 'weight' a traditional adiposity risk factor predictor of balance performance.

Exploring Obesity and Associated Health Conditions among Doctors in Khulna City

Background: Obesity is a global health concern with increasing prevalence and adverse health implications. While healthcare professionals play a critical role in promoting health and well-being, doctors themselves may be susceptible to obesity and its associated health conditions. Objectives: This study employed a cross-sectional design to collect data on obesity and associated health conditions among doctors in Khulna City. Methods: The study targeted doctors practicing at Khulna Medical College. A random sampling method will be employed to ensure representation. Data were collected from 110 doctors through a combination of self-report measures, BMI, and medical records review. Participants' age, gender, and years of medical practice including personal habits were recorded using a structured questionnaire through face-to-face interviews. Results: in the total sample of 110 respondents, there were 62 males (56.36%) and 48 females (43.64%). Mean age 40.25 and SD±7.9. In the "No smoker" category, there were 8 male respondents, accounting for 7.27% of the total, and 48 female respondents, representing 43.64% of the total. In the BMI range of 18.5-24.9, there were 34 respondents (30.91% of the total). Out of these, 23 were male (20.91% of the total) and 11 were female (10% of the total). Conclusion: By addressing the issue of obesity among doctors, it can contribute to their health, enhance their professional capacity, and ultimately improve healthcare outcomes.

Fecal Microbiota Transplantation for Weight and Glycemic Control of Obesity as Well as the Associated Metabolic Diseases: Meta-Analysis and Comprehensive Assessment.

Objectives: An analysis of the weight and blood glucose management associated with fecal microbiota transplantation (FMT) as well as metabolic diseases associated with FMT was conducted by the authors in order to provide clinical recommendations regarding the treatment of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods: We searched PubMed, Embase, and the Cochrane Library for papers that were published between the creation of the database and October 2022. We reviewed research that investigated how FMT affected weight and glycemic management in cases of obesity and metabolic conditions that are related to obesity. Studies that were published more than once, lacked the entire text, included insufficient information, or were impossible to extract data from were excluded. Additionally, case reports, reviews, and systematic reviews were excluded from the analysis. In order to analyze the data, STATA 15.1 was used. Outcomes: When we combined all of our findings, we discovered that pooled outcomes showed that weight levels (WMD equals -4.77, 95%CI: -7.40~-2.14), BMI levels (WMD equals -1.59, 95%CI: -2.21~-0.97), HOMA-IR (WMD equals -0.79, 95%CI: -1.57~-0.00), and HbA1c (WMD equals -0.65, 95%CI: -0.75~-0.55) after FMT treatment were significantly lower than before treatment. However, FMT treatment may have no effect on glucose and insulin levels in obese patients at fasting and related metabolic diseases. Additionally, subgroup analysis outcomes found that FMT significantly reduced fasting blood glucose in people with diabetes. Conclusions: As a weight loss and glycemic control therapy, FMT helps to prevent and treat metabolic problems linked to obesity, and is a viable alternative to bariatric surgery for patients who do not wish to undergo the procedure.

Effects of Smoking on Serum Ferritin levels in adult population living in Sulaymaniyah, Iraq: A Retrospective Cross-sectional Study

Objectives: The current study aims to examines the effect of smoking on serum ferritin levels of adult populations in Sulaymaniyah. &#x0D; Methods: The study was conducted on 80 smokers and 20 non-smokers, totally 100 persons. Their ages ranged from 18 to 65 years.&#x0D; Results: This study showed that the majority of smokers had elevated ferritin levels. A p-value of less than 0.05 indicated a significant difference in ferritin levels between smokers and non-smokers groups. The average ferritin level among smoker group was 227.40 mg/L, while the average ferritin level among non-smokers group was 118.3 mg/L. Regarding the associated between age groups and average ferritin levels, the average ferritin level is highest in the age groups between 51-61 years old. In addition, obesity may play a role in raising ferritin levels, people with obese conditions (BMI &gt; 30) have the highest average ferritin levels than others.&#x0D; Conclusion: This study provides evidence that smoking negatively affect serum ferritin levels, since increases in mean ferritin levels are very striking in smoking and obese group.

EVALUATION OF THERAPEUTIC EFFICACY OF ALOE VERA GEL FOR EXCISIONAL WOUND HEALING MECHANISM USING ANIMAL MODEL

Wound-healing diseases are considered significant clinical issues in patients, which become more complicated in association with obesity, diabetes mellitus, and high blood pressure conditions. Various therapeutic options were available for the wound-repairing process. The current study project evaluated the healing properties of Aloe Vera gel on epidermal wounds in rats. Experimental animals (adult rats) were divided into groups A, B, and C with equal distribution. These groups represent treatment, without treatment, and control, respectively. A pair of wounds measuring 2cm x 2cm each was created hygienically on the back of each rat lateral to the spinal cord. The wounds were treated with homogenized Aloe Vera gel, while the injuries in the second group were treated with normal saline. Blood samples were collected on days 21 for hematology analysis with a standard method. Animals in group ‘A’ had significantly faster healing with shorter days of skin fall-off than the control and untreated group. Further biochemical changes in the packed cell volume, mean corpuscular volume, lymphocyte and neutrophil counts also showed significant results compared to the control group. The study concluded that Aloe Vera effectively treated epidermal wounds in adult rat models. An improvement occurred in the hematological profile of the experimental animals. These findings will go a long way in expanding the horizon of the clinical application of this plant in solving wound-healing problems in humans and other animal species.

Pyridylnidulin exerts anti-diabetic properties and improves non-alcoholic fatty liver disease in diet-induced obesity mice.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the metabolic disorders related to the pathophysiology of type 2 diabetes mellitus (T2DM). Therapeutic strategies are focused on the improvement of energy balance and lifestyle modification. Additionally, the derivative of the bioactive fungal metabolite is of interest to provide health benefits, especially in obese and pre-diabetic conditions. In our screening of anti-diabetic compounds from fungal metabolites and semisynthetic derivatives, a depsidone derivative, namely pyridylnidulin (PN), showed potent glucose uptake-inducing activity. The present study aimed to investigate the liver lipid metabolism and anti-diabetic properties of PN in diet-induced obesity mice. Methods: Male C57BL/6 mice were induced obesity and pre-diabetic conditions by dietary intervention with a high-fat diet (HFD) for 6 weeks. These obese mice were orally administered with PN (40 or 120 mg/kg), metformin (150 mg/kg), or vehicle for 4 weeks. Glucose tolerance, plasma adipocytokines, hepatic gene and protein expressions were assessed after treatment. Results: Improved glucose tolerance and reduced fasting blood glucose levels were found in the PN and metformin-treated mice. Additionally, hepatic triglyceride levels were consistent with the histopathological steatosis score regarding hepatocellular hypertrophy in the PN and metformin groups. The levels of plasma adipocytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were reduced in the PN (120 mg/kg) and metformin-treated mice. In addition, hepatic gene expression involved in lipid metabolism, including lipogenic enzymes was significantly reduced in the PN (120 mg/kg) and metformin-treated mice. The increased protein expression levels of phosphorylated AMP-activated protein kinase (p-AMPK) was also found in PN and metformin-treated mice. Discussion: Considering the increased p-AMPK protein expression levels in PN and metformin-treated mice were revealed as the underlying mechanisms to improve metabolic parameters. These results suggested that PN provided the health benefit to slow the progression of NAFLD and T2DM in obese and pre-diabetic conditions.

CEBP-β and PLK1 as Potential Mediators of the Breast Cancer/Obesity Crosstalk: In Vitro and In Silico Analyses.

Over the last two decades, obesity has reached pandemic proportions in several countries, and expanding evidence is showing its contribution to several types of malignancies, including breast cancer (BC). The conditioned medium (CM) from mature adipocytes contains a complex of secretes that may mimic the obesity condition in studies on BC cell lines conducted in vitro. Here, we report a transcriptomic analysis on MCF-7 BC cells exposed to adipocyte-derived CM and focus on the predictive functional relevance that CM-affected pathways/processes and related biomarkers (BMs) may have in BC response to obesity. CM was demonstrated to increase cell proliferation, motility and invasion as well as broadly alter the transcript profiles of MCF-7 cells by significantly modulating 364 genes. Bioinformatic functional analyses unraveled the presence of five highly relevant central hubs in the direct interaction networks (DIN), and Kaplan-Meier analysis sorted the CCAAT/enhancer binding protein beta (CEBP-β) and serine/threonine-protein kinase PLK1 (PLK1) as clinically significant biomarkers in BC. Indeed, CEBP-β and PLK1 negatively correlated with BC overall survival and were up-regulated by adipocyte-derived CM. In addition to their known involvement in cell proliferation and tumor progression, our work suggests them as a possible "deus ex machina" in BC response to fat tissue humoral products in obese women.

Examining the associations between testosterone and biomarkers as men age.

Testosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone-binding globulin (SHBG), using a large nationally-representative data set (National Health and Nutrition Examination Survey; NHANES). NHANES is a cross-sectional survey, physical examination, and laboratory evaluation of a nationally-representative sample of a non-institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013-2014 and NHANES 2015-2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA-IR), insulin, glucose, and age. An overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA-IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA-IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre-diabetic HOMA-IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables. The results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG.

The relationship between internalized weight stigma and physical and mental health-related quality of life in a large sample of women: a structural equation modeling analysis

PurposeHealth-related quality of life (HRQOL) refers to an individual's perception of their physical and mental health status over time. Although emerging evidence has documented a negative association between weight stigma (i.e., negative weight-related attitudes and beliefs towards individuals with overweight or obesity) and mental HRQOL, its influence on physical HRQOL still needs to be fully clarified. This study aims to investigate the impact of internalized weight stigma on mental and physical HRQOL by employing a structural equation modeling (SEM) approach.MethodsThe Short Form Health Survey 36 (SF-36) and the Weight Bias Internalization Scale (WBIS) were administered to a sample of 4450 women aged 18–71 (Mage = 33.91 years, SD = 9.56) who self-identified in a condition of overweight or obesity (MBMI = 28.54 kg/m2; SD = 5.86). Confirmatory factor analysis (CFA) was conducted to assess the dimensionality of the scales before testing the proposed structural model.ResultsAfter establishing the adequacy of the measurement model, SEM results revealed that internalized weight stigma was significantly and negatively associated with both mental (β = − 0.617; p < 0.001) and physical (β = − 0.355, p < 0.001) HRQOL.ConclusionThese findings offer additional support to prior research by confirming the association between weight stigma and mental HRQOL. Moreover, this study contributes to the existing literature by strengthening and extending these associations to the physical HRQOL domain. Although this study is cross-sectional in nature, it benefits from a large sample of women and the use of SEM, which offers advantages over traditional multivariate techniques, e.g., by explicitly accounting for measurement error.Level of evidence: Level V, descriptive cross-sectional study.

225-LB: Reciprocal Regulatory Interactions of Adipocytes and B Lymphocytes

Obesity, a global health problem, leads to chronic inflammation of adipose tissue (AT), an immune-mediated process linked to metabolic dysfunction and disease, including type II diabetes mellitus. Adipocytes, the most abundant cellular constituent of AT, store lipids and secrete adipokines, a group of hormone-like molecules such as adiponectin and adipsin that regulate metabolism and immune cell functions. In mouse models of diet-induced obesity, distinct subsets of B lymphocytes have been implicated in both exacerbating and mitigating AT inflammation and insulin resistance, but the immunoregulatory mechanisms underlying these effects are incompletely understood. Similarly, whether B lymphocytes and adipocytes engage in regulatory interactions with each other is not known. To investigate this question, we performed in vitro co-culture studies using murine 3T3-L1 adipocytes and I.29µ+ B cells, a murine B cell lymphoma that initiates robust secretion of IgM antibodies and the anti-inflammatory cytokine interleukin (IL)-10 upon activation by lipopolysaccharide (LPS). The induction of IgM and IL-10 secretion was markedly attenuated when I.29µ+ B cells were stimulated with LPS while co-cultured in direct contact with 3T3-L1 adipocytes. This inhibitory effect was also observed, albeit to a lesser degree, when the two cell types were co-cultured but separated by a semipermeable membrane. Conversely, secretion of adiponectin and adipsin by 3T3-L1 adipocytes was reduced when the adipocytes were co-cultured with I.29µ+ B cells, both in direct contact and when separated by a semipermeable membrane. This reduction of adipokine output was observed in both the absence and presence of LPS to activate the B cells. These data support the hypothesis that B lymphocytes and adipocytes can engage in reciprocal interactions that modulate the functions of these two secretory cell types and, in turn, may influence AT homeostasis and inflammation in healthy and obese states. Disclosure J. W. Brewer: None. R. L. Judd: None. M. K. Allman: None. S. R. Carroll: None. S. Granger: None. A. Hall: None. K. Pownall: None. J. Quintana: None. N. Arellano rangel: None. J. Thomas: None. Funding Edward Via College of Osteopathic Medicine Center for One Health

1628-P: Role of CD38 in the Regulation of Muscle Stem Cell Functions in Aged Mice

Skeletal muscle repair and regeneration is a complex process and is known to be delayed with aging, diabetes and obesity. This is in part due to infiltration of inflammatory macrophages which can delay the recovery process. Both macrophages and satellite cells require nicotinamide adenine dinucleotide (NAD+) for their biological functions. Aging-induced decline in NAD+ have been shown to worsen insulin resistance and muscle dysfunction. CD38 is an ectoenzyme that degrades NAD+ and is increased in inflammatory macrophages in aging, obesity and other insulin-resistant states. However, how inhibition of CD38 affects satellite cell functions in aged or obese mice, remains unknown. Here, we utilized aged CD38 knockout mice to assess the role of this protein and NAD+ in the recovery process in injured muscle. CD38 KO mice were found to be resistant to diet-induced obesity and had improved insulin sensitivity. Our data show that genetic deletion of CD38 in aged mice increased NAD+ levels and thus enhanced muscle stem/satellite cells differentiation and promote myogenesis. Deletion of CD38 also resulted in an enhanced number of regenerating myofibers. Furthermore, we found that deletion of CD38 significantly reduces fibrosis of muscle and also improved limb grip strength. Pharmacological inhibition of CD38 in C2C12 myoblasts and ex-vivo primary myoblasts significantly increased NAD+ levels and also enhanced the differentiation of satellite cells into myoblasts and myofibers. We, therefore, examined the rescue effects of 78c (CD38i) on human recombinant CD38 (hCD38) inhibition of muscle stem cells. Administration of hCD38 inhibited expression of MyoD and MyoG in primary myoblasts, while this effect was rescued through 78c treatment. Taken together, these data demonstrate that restoration of NAD+ levels either through genetic deletion/pharmacological inhibition of CD38 can improve muscle stem cell functions and muscle regeneration and might promote muscle regeneration in obesity, type 2 diabetes, and aging. Disclosure A.Nawaz: None. K.Yaku: None. I.Jeelani: None. K.Tobe: Other Relationship; MSD K.K., Novo Nordisk Pharma Ltd., Takeda Pharmaceutical Company Limited, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Suntory Global Corporation, Ltd.,, Taiho Pharmaceutical Co. Ltd., Japan Diabetes Foundation, Japan Association for Diabetes Education and Care. T.Nakagawa: None.

1685-P: Comparison of Obesity and Aging Signatures in Murine Adipose Tissue at Single-Cell Resolution

Obesity and aging are major risk factors for various diseases and thus represent heavy socioeconomic burden to global healthcare. The two processes share similar, if not convergent, phenotypes, and increasing evidence suggests that one accelerates the other. Both obesity and aging are associated with insulin resistance, chronic low-grade inflammation and dysfunction of systemic energy homeostasis. However, there are many differences as well and the molecular mechanisms behind such similarities and differences remain unclear. Dysfunction of adipose tissue plays a significant role in both processes. Many studies have characterized adipose tissue of lean and obese mice at single-cell level, but obese and aged adipose tissue have not been directly compared side-by-side. Here, we compare single-cell transcriptomics of visceral (VAT) and subcutaneous (SAT) white adipose tissue in lean, diet-induced obesity, and aged conditions. In obese VAT, the relative frequency of macrophages increased, while that of lymphocytes decreased as expected. However, such myeloid shift was not observed in aged VAT. Metabolically, TREM2+ “lipid-associated macrophages”, which is known to increase in obese VAT, did not increase in aged VAT. Clustering of mesenchymal progenitor cells revealed depot-specific differences in previously reported cell subtypes. More cells were in a further differentiated, committed stage in VAT than in SAT. CD142+ CLEC11A+ “Aregs,” which were previously found to inhibit adipogenesis, increased in aged VAT and obese SAT. Interestingly, the frequency of endothelial cells in obese or aged state drastically decreased in SAT but not in VAT. Our comparative single-cell transcriptome atlas provides a detailed resource to analyze functional genomics behind obesity and aging. Disclosure E.Lee: None. D.Kang: None. J.Suh: None.

173-LB: Circulating Calprotectin Is Increased in Children with T1D and Obesity—Implications for T1D Progression and Outcome

Purpose: Circulating calprotectin is elevated in inflammatory disorders and is a biomarker of severity in inflammatory rheumatic and bowel diseases. Calprotectin has immunomodulatory properties that may influence the progression and outcome of inflammatory diseases. Calprotectin is elevated in children with obesity, but its levels in children with T1D co-morbid with obesity remain unexplored. We examined the levels of circulating calprotectin in children with T1D and obesity and compared these levels with those of children with normal weight as well as those with obesity and T2D or children with obesity only (no prediabetes or T2D). Methods: Sixty-four children (aged 5-13 years) were included. Participants' characteristics included being of normal weight (body mass index, BMI &amp;lt;85th percentile; n = 12), having obesity (BMI ≥95th percentile) with T1D (n = 4), obesity with T2D (n = 8), or having obesity without prediabetes or diabetes (n = 40). Clinical markers were assessed using established procedures on peripheral blood. The levels of calprotectin were quantified using commercially available ELISA kits. Results: Circulating calprotectin was significantly (P = 0.0044) higher in children with T1D and obesity, as well as in children with T2D and obesity (P = 0.02), compared to healthy children with normal weight. There was no difference in calprotectin levels between children with T1D and obesity compared to those with T2D and obesity or obesity without prediabetes or diabetes. Conclusion: Increased calprotectin in children with T1D (as well as T2D) is due to the obese state and is not further increased by having diabetes. Given the immunomodulatory properties of calprotectin, obesity in children with T1D might hasten disease progression, resulting in a worse outcome. These findings highlight the need for tailored obesity prevention in children with high risk for T1D and emphasize the importance of treatment strategies for weight management in children with T1D. Disclosure A. Hasan: None. S. P. Kochumon: None. I. D. Albasiri: None. S. Albeloushi: None. E. S. Alozairi: None. F. Almulla: None. Funding Kuwait Foundation for the Advancement of Sciences