👤 Museer Lone

Sphingolipids (SLs) are structurally diverse lipids that are defined by the presence of a long-chain base (LCB) backbone. Typically, LCBs contain a single Δ4E double bond (DB) (mostly d18:1), whereas the dienic LCB sphingadienine (d18:2) contains a second DB at the Δ14Z position. The enzyme introducing the Δ14Z DB is unknown. We analyzed the LCB plasma profile in a gender-, age-, and BMI-matched subgroup of the CoLaus cohort ( Show less

Recent evidence has emerged that cancer cells can use various metabolites as fuel sources. Restricting cultured cancer cells to sole metabolite fuel sources can promote metabolic changes leading to enhanced glycolysis or mitochondrial OXPHOS. However, the effect of metabolite-restriction on non-transformed cells remains largely unexplored. Here we examined the effect of restricting media fuel sources, including glucose, pyruvate or lactate, on the metabolic state of cultured human dermal fibroblasts. Fibroblasts cultured in lactate-only medium exhibited reduced PDH phosphorylation, indicative of OXPHOS, and a concurrent elevation of ROS. Lactate exposure primed fibroblasts to switch to glycolysis by increasing transcript abundance of genes encoding glycolytic enzymes and, upon exposure to glucose, increasing glycolytic enzyme levels. Furthermore, lactate treatment stabilized HIF-1α, a master regulator of glycolysis, in a manner attenuated by antioxidant exposure. Our findings indicate that lactate preconditioning primes fibroblasts to switch from OXPHOS to glycolysis metabolism, in part, through ROS-mediated HIF-1α stabilization. Interestingly, we found that lactate preconditioning results in increased transcript abundance of MYC and SNAI1, key facilitators of early somatic cell reprogramming. Defined metabolite treatment may represent a novel approach to increasing somatic cell reprogramming efficiency by amplifying a critical metabolic switch that occurs during iPSC generation. Show less

To investigate the association of -1131T>C polymorphism of apolipoprotein A5 (APOA5) with metabolic syndrome and associated traits. A cross-sectional comparative study. Department of Physiology, University of Health Sciences Lahore, from July 2016 to December 2017. Study population included 200 cases of metabolic syndrome and 200 controls. Cases were selected from Sheikh Zayed Hospital, Lahore according to the International Diabetes Federation guidelines. Fasting blood sample of 8 ml was taken for biochemical and genetic analysis, as per objective. Demographics, waist circumferance and blood pressure (BP) were also recorded. Subjects with metabolic syndrome had significantly higher waist circumference, BP, serum lipid and glycemic parameters as compared to the controls (p<0.001). The observed frequency of APOA5-1131T>C genotype TT was 180 (45%), 202 (50.5%) for TC and 18 (4.5%) for CC. Minor C allele frequency of APOA5-1131T>C variant was significantly higher in metabolic syndrome as compared to the controls (0.33 vs. 0.26: p = 0.031*). In the Dominant genotype model (TC+CC vs. TT), 'TC+CC' genotype was significantly associated with the increased risk of metabolic syndrome (OR: 1.50, CI: 1.01-2.23, p = 0.044*). Waist circumference and fasting triglyceride levels were significantly higher in 'TC +CC' genotype as compared to the 'TT' in metabolic syndrome and controls (p = <0.001 and 0.043; p = 0.022 and 0.006). There was significant association of the 'TC+CC' genotype of APOA5 -1131T>C with the increased risk of Met S and the association remained significant after controlling for age and gender. Show less

The present study aimed to determine the association of adrenergic receptor beta-3 (ADRB3) rs4994 T>C and liver X receptor alpha (LXR-α) rs12221497 G>A polymorphism with metabolic syndrome (Met S) and the related traits in Pakistanis. Patients of Met S were recruited from the Endocrinology and Diabetic Clinic of Sheikh Zayed Hospital Lahore, over the time span of 6 months from July to December 2016. Single-nucleotide polymorphism (SNP) of ADRB3 was determined by restriction fragment length polymorphism and of LXR-α by amplification refractory mutation system polymerase chain reaction. The frequency of TT variant of ADRB3 T>C in Met S was 69 (34.5%) and in controls 89 (44.5%), frequency of TC 103 (51.5%) and 96 (48%), and of CC 28 (14%) and 15 (7.5%), respectively. In the recessive model (CC: TT + TC), CC genotype was found to be associated with the increased risk of Met S (P = 0.027; odds ratio [OR] = 2.09; confidence interval [CI] =1.08-4.03) and the association remained significant after controlling for the confounders such as age and sex. The frequency of GG variant of LXR-α G>A in Met S was 35 (17.5%) and in controls 15 (7.5%), GA 129 (64.5%) and 137 (68.5%), and AA 36 (18%) and 48 (24%), respectively. In the recessive model (GG: GA + AA), GG genotype was found to be associated with the increased risk of Met S (P = 0.004; OR = 2.52; CI = 1.33-4.80) and the association remained significant after controlling for the confounders such as age and sex. It was concluded that SNP of ADRB3 (190 T>C) and LXR-α (-115 G>A) were associated with the risk of Met S and might increase the susceptibility to the obesity-related traits. Show less