Identifying Potential biomarkers of insulin sensitivity and insulin resistance in obese patients

Obesity is a major risk factor for insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain insulin sensitivity and show a lower risk of insulin resistance and T2DM. Our overall aim was to investigate the molecular mechanisms underlying the protective phenotype of obese insulin sensitive (OIS) individuals to help designing novel diagnostic and therapeutic strategies targeting obese insulin resistant (OIR) and T2DM counterparts. To achieve our aim, OMICS techniques, including metabolomics and lipidomics of blood and adipose tissues respectively, were utilized to investigate the molecular pathways differentiating OIS from OIR and T2DM. Blood metabolic profiling identified several metabolites associated with increased risk of T2DM including novel phospholipid metabolites. Adipose tissue lipidomics profiling revealed novel triacyclglycerols and fatty acids that were significantly altered with disease progression, including C12:0 and C18 fatty acids. Finally, we investigated the potential role of the prominent environmental pollutants polybrominated diphenyl ethers (PBDEs) in obesity-associated insulin resistance by measuring their bioaccumulation in adipose tissues from OIS and the OIR individuals. Our novel data indicated that PBDEs 99, 28, and 47 were significantly higher in OIR individuals compared to their OIS counterparts. Treatment of preadipocytes from OIS individuals with PBDE28 caused inhibition of insulin signaling, suggesting a functional role. The identified metabolites shed light on the molecular pathways potentially underlying the protective phenotype of OIS. Future studies will address the functionality of these metabolites in relation to insulin resistance and identify those that could potentially be used as diagnostic and/or therapeutic targets

The Impact of the Economic Blockade on Trade in Qatar

Qatar imports in June were valued at 5.9 billion QAR, which shows a 40% decline from the same month in 2016. The drop in imports continued in July with 35% from their year to year level. Imports rebounded in the month of August with only 7.8% difference from last year, it is considered a major recovery from the past two months

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

Metabolomics Approaches for the Diagnosis, Treatment, and Better Disease Management of Viral Infections

Metabolomics is an analytical approach that involves profiling and comparing the metabolites present in biological samples. This scoping review article offers an overview of current metabolomics approaches and their utilization in evaluating metabolic changes in biological fluids that occur in response to viral infections. Here, we provide an overview of metabolomics methods including high-throughput analytical chemistry and multivariate data analysis to identify the specific metabolites associated with viral infections. This review also focuses on data interpretation and applications designed to improve our understanding of the pathogenesis of these viral diseases.This research was funded by the Qatar National Research Fund (QNRF), grant number (NPRP11S-1212-170092).Scopu

Studies on vascular response to full superantigens and superantigen derived peptides:Possible production of novel superantigen variants with less vasodilation effect for tolerable cancer immunotherapy

Superantigens (SAgs) are a class of antigens that cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release and causing symptoms similar to sepsis, e.g. hypotension and subsequent hyporeactivity. We investigated the direct effect of SAgs on vascular tone using two recombinant SAgs, SEA and SPEA. The roles of Nitric Oxide (NO) and potentially hyperpolarization, which is dependent on the K + channel activation, were also explored. The data show that SEA and SPEA have direct vasodilatory effects that were in part NO-dependent, but completely dependent on activation of K + channels. Our work also identified the functional regions of one of the superantigens, SPEA, that are involved in causing the vasodilation and possible hypotension. A series of 20 overlapping peptides, spanning the entire sequence of SPEA, were designed and synthesized. The vascular response of each peptide was measured, and the active peptides were identified. Our results implicate the regions, (61–100), (101–140) and (181–220) which cause the vasodilation and possible hypotension effects of SPEA. The data also shows that the peptide 181–220 exert the highest vasodilation effect. This work therefore, demonstrates the direct effect of SAgs on vascular tone and identify the active region causing this vasodilation. We propose that these three peptides could be effective novel antihypertensive drugs. We also overexpressed, in E.coli, four superantigens from codon optimized genes

Metabolomics Approaches for the Diagnosis, Treatment, and Better Disease Management of Viral Infections

Metabolomics is an analytical approach that involves profiling and comparing the metabolites present in biological samples. This scoping review article offers an overview of current metabolomics approaches and their utilization in evaluating metabolic changes in biological fluids that occur in response to viral infections. Here, we provide an overview of metabolomics methods including high-throughput analytical chemistry and multivariate data analysis to identify the specific metabolites associated with viral infections. This review also focuses on data interpretation and applications designed to improve our understanding of the pathogenesis of these viral diseases

Does consanguinity lead to decreased incidence of breast cancer?

Background In the Middle East region, consanguinity remains to be a central feature where it has shown an increasing trend Breast cancer is an extremely complex disease, characterized by a progressive multistep process caused by interactions of both environmental and genetic factors AIM The aim of this study was to examine the possible effect of consanguinity on the risk of breast cancer in a population with a high rate of consanguinity and find the associated risk-modifying factors Subjects and methods The study included 167 Qatari and other Arab expatriates women with breast cancer and 341 age and ethnicity matched control women A questionnaire that included the socio-demographic information, type of consanguinity, medical history, life style habits, dietary intake and tumor grade was designed to collect, the information of cases and controls A total number of 214 breast cancer patients were approached and 167 cases completed the questionnaires with a response rate of 78% Of the 417 healthy women who agreed to participate in this study. 341 responded to the questionnaire (81 8%) Results The study revealed that the rate of parental consanguinity was lower in breast cancer patients (24%) than in controls (32 3%) (p = 0 062) Female controls were slightly younger (46 5 +/- 11 9) than breast cancer patients (48 4 +/- 10.7) Breast cancer incidence was significantly higher in Qatari women (34 1%) compared to other Arab women (65 9%) (p = 0 034) A significant difference was noted only in occupation of the studied women between cases and controls (p < 0 001) Overweight (46 7%) and obesity (32 9%) were significantly higher in female breast cancer patients compared to controls (p = 0 028) Overall, the mean coefficient of consanguinity was lower in breast cancer patients (0 014) than in controls (0 018) (p = 0 0125) Family history of breast cancer was significantly more often in breast cancer patients (14 4%) than in controls (6 2%) (p = 0 002) However, the family history of breast cancer was more often positive in cases of non-consanguineous parents (15 7%) than cases of consanguineous parents (10 0%) Conclusion The present study revealed the lack of association between of breast cancer and the parental consanguinity in Arab women residing in Qatar The family history of breast cancer and the body mass index (BMI) are highly associated with breast cancer (C) 2010 Elsevier Ltd. All rights reserve

Impact of Consanguinity on Cancer in a Highly Endogamous Population

Background: Many epidemiological studies have indicated that inbreeding has little or no effect on the incidence of cancer. Due to the high prevalence of consanguinity in Qatar (54%), its influence may nevertheless be of special importance. Aim: The aim of this study was to examine whether parental consanguinity affects the risk of cancer in a local Arab highly inbred population. Design: Matched case-control study. Setting : The study was carried out in Al-Amal cancer hospital and primary health care centers in Qatar over a period from August 2008 to February 2009. Subjects and Methods: The study included 370 Qataris and other Arab expatriates with various types of cancers and 635 controls matched by age and ethnicity. A questionnaire that included sociodemographic information, type of consanguinity, medical history, and tumor grade was designed to collect the information of cases and controls. Results: The study revealed that the rate of parental consanguinity was similar in both cases (29.5%) and controls (29.9%) with a higher inbreeding coefficient in controls (0.017 +/- 0.03), compared to cancer patients (0.0155 +/- 0.03). Other Arab expatriates had a higher incidence of cancer (61.1%) than Qataris (38.9%). The inbreeding coefficient was higher in male cancer patients (0.0189 +/- 0.03), but lower in female cancer patients (0.014 +/- 0.03) as compared to controls. Controls were more inbred in the overall studied subjects (23.6%) and women (23.8%) than cases. The coefficient of inbreeding was lower in patients with breast (0.014), skin (0.012), thyroid (0.008) and female genital (0.014) cancers, whereas it was higher in cases for leukemia and lymphoma (0.018), colorectal (0.025) and prostate (0.017), with no significant difference between cases and controls. No significant differences were observed between cases and controls in the parental consanguinity, mean coefficient of inbreeding and proportion of more inbred subjects. Conclusions: The study findings revealed that although the consanguinity rate is high in our Arab population, it has no effect on the incidence of cancers overall. However, there was an increased risk found for leukemia and lymphoma, colorectal and prostate cancer groups, but a reduced risk in breast, skin, thyroid and female genital cancer groups

Triglyceride profiling in adipose tissues from obese insulin sensitive, insulin resistant and type 2 diabetes mellitus individuals

Abstract Background Lipid intermediates produced during triacylglycerols (TAGs) synthesis and lipolysis in adipocytes interfere with the intracellular insulin signaling pathway and development of insulin resistance. This study aims to compare TAG species and their fatty acid composition in adipose tissues from insulin sensitive (IS), insulin resistant (IR) and type 2 diabetes mellitus (T2DM) obese individuals. Methods Human subcutaneous and omental adipose tissue biopsies were obtained from 64 clinically characterized obese individuals during weight reduction surgery. TAGs were extracted from the adipose tissues using the Bligh and Dyer method, then were subjected to non-aqueous reverse phase ultra-high performance liquid chromatography and full scan mass spectrometry acquisition and data dependent MS/MS on LTQ dual cell linear ion trap. TAGs and their fatty acid contents were identified and compared between IS, IR and T2DM individuals and their levels were correlated with metabolic traits of participants and the adipogenic potential of preadipocyte cultures established from their adipose tissues. Results Data revealed 76 unique TAG species in adipose tissues identified based on their exact mass. Analysis of TAG levels revealed a number of TAGs that were significantly altered with disease progression including C46:4, C48:5, C48:4, C38:1, C50:3, C40:2, C56:3, C56:4, C56:7 and C58:7. Enrichment analysis revealed C12:0 fatty acid to be associated with TAGs least abundant in T2DM whereas C18:3 was found in both depleted and enriched TAGs in T2DM. Significant correlations of various adipose tissue-derived TAG species and metabolic traits were observed, including age and body mass index, systemic total cholesterol, TAGs, and interleukin-6 in addition to adipogenic potential of preadipocytes derived from the same adipose tissues. Conclusion Pilot data suggest that adipose tissues from obese IR and T2DM individuals exhibit TAG-specific signatures that may contribute to their increased risk compared to their IS counterparts. Future experiments are warranted to investigate the functional relevance of these specific lipidomic profiles

Metabolic signature of obesity-associated insulin resistance and type 2 diabetes.

Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality