Mediators of Impaired Adipogenesis in Obesity-Associated Insulin Resistance and T2DM

Obesity has become a global health issue due to its high prevalence and associated comorbidities including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Obesity is associated with the expansion of adipose tissues through hypertrophy of mature adipocytes and differentiation of local preadipocytes in a process known as adipogenesis to store excess triacylglycerols (TAGs). Impairment of adipogenesis leads to ectopic fat deposition in skeletal muscles, liver, and kidneys, triggering IR in these tissues and increased risk of T2DM. Many factors contribute to impaired adipogenesis including obesity-associated mild chronic inflammation, oxidative stress, and fatty acid signaling. This review summarizes recent literature covering mediators of impaired adipogenesis and underlying molecular pathways

From an Apple to a Pear: Moving Fat around for Reversing Insulin Resistance.

Type 2 diabetes (T2D) is a chronic condition where the body is resistant to insulin, leading to an elevated blood glucose state. Obesity is a main factor leading to T2D. Many clinical studies, however, have described a proportion of obese individuals who express a metabolically healthy profile, whereas some lean individuals could develop metabolic disorders. To study obesity as a risk factor, body fat distribution needs to be considered rather than crude body weight. Different individuals' bodies favor storing fat in different depots; some tend to accumulate more fat in the visceral depot, while others tend to store it in the femoral depot. This tendency relies on different factors, including genetic background and lifestyle. Consuming some types of medications can cause a shift in this tendency, leading to fat redistribution. Fat distribution plays an important role in the progression of risk of insulin resistance (IR). Apple-shaped individuals with enhanced abdominal obesity have a higher risk of IR compared to BMI-matched pear-shaped individuals, who store their fat in the gluteal-femoral depots. This is related to the different adipose tissue physiology between these two depots. In this review, we will summarize the recent evidence highlighting the underlying protective mechanisms in gluteal-femoral subcutaneous adipose tissues compared to those associated with abdominal adipose tissue, and we will revise the recent evidence showing antidiabetic drugs that impact fat distribution as they manage the T2D condition.This research was funded by the Qatar National Research Fund (QNRF), grant number NPRP13S-1230-190008

Prevalence and Predictors of Insulin Resistance in Non-Obese Healthy Young Females in Qatar

The state of Qatar suffers from diabetes epidemic due to obesity-associated metabolic syndrome. However, the prevalence of insulin resistance prior to obesity, which could play an important role in the high prevalence of diabetes, has not yet been described. This study aims to compare the prevalence of insulin resistance in apparently healthy non-obese and obese participants from Qatar and identify the predictors of insulin resistance in different body massindex(BMI)-groups. In this cross-sectional study, 150 young healthy females from Qatar were dichotomized into four groups (underweight, normal weight, overweight and obese) based on their BMI. Anthropometric measures as well as fasting plasma levels of lipids, adipokines, blood glucose and insulin were recorded. The prevalence of insulin resistance as per homeostatic model assessment of insulin resistance (HOMA-IR) was estimated and differences between insulin sensitive and insulin resistant were compared. Linear models were used to identify predictors of insulin resistance in every BMI group. Prevalence of insulin resistance in non-obese healthy females from Qatar ranges between 7% and 37%and increases with BMI. Overall, predictors of insulin resistance in the Qatari population are triglycerides/high-density lipoprotein (HDL) ratio and free fat mass but vary according to the BMI group. The main predictors were triglycerides in normal weight, triglycerides/HDL in overweight and triglycerides/HDL and interleukin-6 (IL-6) in obese individuals. The high prevalence of insulin resistance in non-obese Qataris may partially explain diabetes epidemic. Larger studies are warranted to confirm these findings and identify underlying causes for insulin resistance in non-obese individuals in Qatar, aiming at targeted intervention before diabetes onsetThis project was funded by Qatar University (grant number QUST-CAS-FALL-14\15-35). The publication of this article was funded by the Qatar National Library

Editorial: OMICS-based approaches in sports research volume II.

OMICS approaches, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, continue to provide invaluable tools for better understanding of the molecular mechanisms underlying various physiological and pathological functions in health and disease. The rapid advancement of these tools and emergence of new ones is progressively filling the gap in our understanding of the complex networks that determine the structure, function, and dynamics of organisms. These advancements have greatly empowered discoveries of novel diagnostic and prognostic biomarkers as well as therapeutic targets, and provided a better guidance to precision and personalized medicine

Profiling the Oral Microbiome and Plasma Biochemistry of Obese Hyperglycemic Subjects in Qatar

The present study is designed to compare demographic characteristics, plasma biochemistry, and the oral microbiome in obese ( = 37) and lean control ( = 36) subjects enrolled at Qatar Biobank, Qatar. Plasma hormones, enzymes, and lipid profiles were analyzed at Hamad Medical Cooperation Diagnostic Laboratory. Saliva microbiome characterization was carried out by 16S rRNA amplicon sequencing using Illumina MiSeq platform. Obese subjects had higher testosterone and sex hormone-binding globulin (SHBG) concentrations compared to the control group. A negative association between BMI and testosterone ( < 0.001, r = -0.64) and SHBG ( < 0.001, r = -0.34) was observed. Irrespective of the study groups, the oral microbiome was predominantly occupied by , , and species. A generalized linear model revealed that the Firmicutes/Bacteroidetes ratio (2.25 ± 1.83 vs. 1.76 ± 0.58; corrected -value = 0.04) was higher, and phylum Fusobacteria concentration (4.5 ± 3.0 vs. 6.2 ± 4.3; corrected -value = 0.05) was low in the obese group compared with the control group. However, no differences in microbiome diversity were observed between the two groups as evaluated by alpha (Kruskal-Wallis ≥ 0.78) and beta (PERMANOVA = 0.37) diversity indexes. Certain bacterial phyla (Acidobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Firmicutes/Bacteroidetes) were positively associated ( = 0.05, r ≤ +0.5) with estradiol, fast food consumption, creatinine, breastfed during infancy, triglycerides, and thyroid-stimulating hormone concentrations. In conclusion, no differences in oral microbiome diversity were observed between the studied groups. However, the Firmicutes/Bacteroidetes ratio, a recognized obesogenic microbiome trait, was higher in the obese subjects. Further studies are warranted to confirm these findings in a larger cohort.Qatar National Research Fun

Impact of Moderate Physical Activity on Inflammatory Markers and Telomere Length in Sedentary and Moderately Active Individuals with Varied Insulin Sensitivity

Introduction: Physical activity-associated immune response plays a crucial role in the aging process. This study aimed to determine the impact of short-term moderate physical activity on cytokine levels, oxidative stress markers, and telomere length in lean/ overweight young subjects. Methods: Fasting blood samples were collected from 368 participants at Qatar Biobank. Based on their homeostatic model assessment of insulin resistance (HOMA-IR), participants were categorized as insulin sensitive (IS) or insulin resistant (IR). Subsequently, they were divided into four groups: sedentary IS (n = 90), sedentary IR (n = 90), moderately active IS (n = 94), and moderately active IR (n = 94). Moderate physical activity was defined as walking at least two days per week for more than 150 minutes, as determined by physical activity questionnaires. Serum samples were analyzed for circulating inflammatory cytokines (IL-1β, IL-1RA, IL-6, IL-10, IL-22, MCP-1/CCL2, TNF-α), as well as antioxidant enzyme levels (SOD and catalase). Telomere lengths were measured in the respective DNA samples. Results: Moderately active IR participants exhibited significantly lower SOD activity, while catalase activity did not show significant differences. Moderately active IS participants had higher IL-6 and IL-10 levels compared to sedentary IS participants, with no significant differences observed in the IR counterparts. Telomere length did not significantly differ between the physically active and sedentary groups. Conclusion: This study highlights the potential anti-inflammatory and anti-oxidative stress effects of moderate physical activity in individuals with insulin sensitivity and insulin resistance. However, no significant changes in telomere length were observed, suggesting a complex relationship between physical activity and the aging process. Further research is needed to fully understand the underlying mechanisms and optimize the balance between anti-inflammation and anti-oxidation through exercise and lifestyle adjustments.</p

Serum NMR-Based Metabolomics Profiling Identifies Lipoprotein Subfraction Variables and Amino Acid Reshuffling in Myeloma Development and Progression

Multiple myeloma (MM) is an incurable hematological cancer. It is preceded by monoclonal gammopathy of uncertain significance (MGUS)—an asymptomatic phase. It has been demonstrated that early detection increases the 5-year survival rate. However, blood-based biomarkers that enable early disease detection are lacking. Metabolomic and lipoprotein subfraction variable profiling is gaining traction to expand our understanding of disease states and, more specifically, for identifying diagnostic markers in patients with hematological cancers. This study aims to enhance our understanding of multiple myeloma (MM) and identify candidate metabolites, allowing for a more effective preventative treatment. Serum was collected from 25 healthy controls, 20 patients with MGUS, and 30 patients with MM. 1H-NMR (Nuclear Magnetic Resonance) spectroscopy was utilized to evaluate serum samples. The metabolite concentrations were examined using multivariate, univariate, and pathway analysis. Metabolic profiles of the MGUS patients revealed lower levels of alanine, lysine, leucine but higher levels of formic acid when compared to controls. However, metabolic profiling of MM patients, compared to controls, exhibited decreased levels of total Apolipoprotein-A1, HDL-4 Apolipoprotein-A1, HDL-4 Apolipoprotein-A2, HDL Free Cholesterol, HDL-3 Cholesterol and HDL-4 Cholesterol. Lastly, metabolic comparison between MGUS to MM patients primarily indicated alterations in lipoproteins levels: Total Cholesterol, HDL Cholesterol, HDL Free Cholesterol, Total Apolipoprotein-A1, HDL Apolipoprotein-A1, HDL-4 Apolipoprotein-A1 and HDL-4 Phospholipids. This study provides novel insights into the serum metabolic and lipoprotein subfraction changes in patients as they progress from a healthy state to MGUS to MM, which may allow for earlier clinical detection and treatment.This work was funded by grants from the Danish Research Council for Independent Research (4183-00268) and the Obel Family Foundation (26145).Scopu

Amniotic stem cells as a source of regenerative medicine to treat female infertility

Impaired reproductive health is a worldwide problem that affects the psychological well-being of a society. Despite the technological developments to treat infertility, the global infertility rate is increasing significantly. Many infertility conditions are currently treated using various advanced clinical approaches such as intrauterine semination (IUI), in vitro fertilization (IVF), and intracytoplasmic injection (ICSI). Nonetheless, clinical management of some conditions such as dysfunctional endometrium, premature ovarian failure, and ovarian physiological aging still pose significant challenges. Stem cells based therapeutic strategies have a long-standing history to treat many infertility conditions, but ethical restrictions do not allow the broad-scale utilization of adult mesenchymal stromal/stem cells (MSCs). Easily accessible, placental derived or amniotic stem cells present an invaluable alternative source of non-immunogenic and non-tumorigenic stem cells that possess multilineage potential. Given these characteristics, placental or amniotic stem cells (ASCs) have been investigated for therapeutic purposes to address infertility in the last decade. This study aims to summarize the current standing and progress of human amniotic epithelial stem cells (hAECs), amniotic mesenchymal stem cells (hAMSCs), and amniotic fluid stem cells (hAFSCs) in the field of reproductive medicine. The therapeutic potential of these cells to restore or enhance normal ovarian function and pregnancy outcomes are highlighted in this study.Open Access funding provided by the Qatar National Library. The authors reported there is no funding associated with the work featured in this article

The Relationship between Changes in MYBPC3 Single-Nucleotide Polymorphism-Associated Metabolites and Elite Athletes’ Adaptive Cardiac Function

Athletic performance is a multifactorial trait influenced by a complex interaction of environmental and genetic factors. Over the last decades, understanding and improving elite athletes’ endurance and performance has become a real challenge for scientists. Significant tools include but are not limited to the development of molecular methods for talent identification, personalized exercise training, dietary requirements, prevention of exercise-related diseases, as well as the recognition of the structure and function of the genome in elite athletes. Investigating the genetic markers and phenotypes has become critical for elite endurance surveillance. The identification of genetic variants contributing to a predisposition for excellence in certain types of athletic activities has been difficult despite the relatively high genetic inheritance of athlete status. Metabolomics can potentially represent a useful approach for gaining a thorough understanding of various physiological states and for clarifying disorders caused by strength–endurance physical exercise. Based on a previous GWAS study, this manuscript aims to discuss the association of specific single-nucleotide polymorphisms (SNPs) located in the MYBPC3 gene encoding for cardiac MyBP-C protein with endurance athlete status. MYBPC3 is linked to elite athlete heart remodeling during or after exercise, but it could also be linked to the phenotype of cardiac hypertrophy (HCM). To make the distinction between both phenotypes, specific metabolites that are influenced by variants in the MYBPC3 gene are analyzed in relation to elite athletic performance and HCM. These include theophylline, ursodeoxycholate, quinate, and decanoyl-carnitine. According to the analysis of effect size, theophylline, quinate, and decanoyl carnitine increase with endurance while decreasing with cardiovascular disease, whereas ursodeoxycholate increases with cardiovascular disease. In conclusion, and based on our metabolomics data, the specific effects on athletic performance for each MYBPC3 SNP-associated metabolite are discussed.M.N. was supported by a QU Internal Grant “QUCG-CMED-22/23-514”. Open access publication of this article is funded by the College of Medicine, QU Health, Qatar University

The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection

BackgroundThe cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection.MethodsSixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models.ResultsData suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively.ConclusionThis pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens