Nicotinamide phosphoribosyltransferase knockdown leads to lipid accumulation in HepG2 cells through the SIRT1-AMPK pathway

Objective: Nicotinamide phosphoribosyltransferase (NAMPT), which is responsible for biosynthesis of nicotinamide adenine dinucleotide (NAD), has a regulatory role in cellular metabolism and thus, might be implicated in non-alcoholic fatty liver disease (NAFLD). This study aimed to show how NAMPT down-regulation in liver cells influences lipid metabolism and sirtiun 1 (SIRT1), as the main NAD-dependent deacetylase enzyme. Materials and Methods: In this experimental study, HepG2 cells were transfected with NAMPT siRNA and hepatic triglyceride (TG) content and SIRT1 deacetylase activity were measured by colorimetric and fluorometric methods, respectively. Gene expression of fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP- 1c) was evaluated by real-time polymerase chain reaction (PCR). Total protein level and the phosphorylated form of acetyl-CoA carboxylase (ACC) and AMP-activated protein kinase (AMPK) were also investigated by western blotting. Results: Knockdown of NAMPT significantly promoted the accumulation of TG in HepG2 cells, accompanied by a remarkable decline in SIRT1 deacetylase activity. A significant rise in the gene expression of two key lipogenic factors, FAS and SREBP-1c was also observed. These effects were also accompanied by decreased phosphorylation of ACC and AMPK. On the other hand, treatment of transfected cells with either NAD, as the SIRT1 substrate or resveratrol, as the SIRT1 activator reversed the outcomes. Conclusion: These results demonstrated a protective role for NAMPT against NAFLD and its involvement in the regulation of de novo lipogenesis through the SIRT1/AMPK pathway. © 2020 Royan Institute (ACECR). All rights reserved

The association between common C677T mutation in methylenetetrahydrofolate reductase gene and the risk of venous thrombosis in an Iranian population

Background: Venous thrombosis is a multicausal disease involving acquired and genetic factors. The prevalence of methylenetetrahydrofolate reductase (MTHFR) C677T genotypes and its association with venous thrombosis is not established in the Iranian population. In this study we investigated a possible association between fasting hyperhomocysteinemia and C677T mutation in the MTHFR gene with venous thrombosis. Materials and Methods: We studied 200 venous thrombotic patients and 100 healthy controls, of similar age and sex. Mutation analysis was carried out by PCR-RFLP, and the homocysteine level was measured by EIA. Results: No significant differences in the frequency of C677T genotypes were observed between patients and controls (P=0.2). The frequency of the T allele was 21 and 27.2 in controls and patients, respectively (odds ratio, 1.27; 95 CI, 0.83-1.94, P=0.15). Fasting homocysteine level was significantly higher in patients than controls (P=0.001). Conclusions: We concluded that hyperhomocysteinemia, but not MTHFR C677T mutation, is a significant risk factor for venous thrombosis in the Iranian population, and measuring the level of homocysteine is less expensive and more useful than the genetic test for the MTHFR mutation

Plasma triglyceride and high density lipoprotein cholesterol are poor surrogate markers of pro-atherogenic chylomicron remnant homeostasis in subjects with the metabolic syndrome

Background: Subjects with metabolic syndrome (MetS) exhibit impaired lipoprotein metabolism and have an increased risk of cardiovascular disease. Although the risk is attributed primarily to the risk associated with individual components, it is also likely affected by other associated metabolic defects. Remnants of postprandial lipoproteins show potent atherogenicity in cell and animal models of insulin resistance and in pre-diabetic subjects with postprandial dyslipidemia. However, few studies have considered regulation of chylomicron remnant homeostasis in MetS per se. This study measured the plasma concentration in Caucasian men and women of small dense chylomicrons following fasting and explored associations with metabolic and anthropometric measures. Methods: A total of 215 Australian Caucasian participants (me dianage62years) were investigated. Of them, 40 participants were classified as having MetS. Apolipoprotein (apo) B-48, an exclusive marker of chylomicrons, metabolic markers and anthropometric measures were determined following an overnight fast.Results: The fasting apo B-48 concentration was 40 % higher in subjects with MetS than those without MetS. In all subjects, triglyceride ( r =0.445, P < 0.0005), non-HDL cholesterol ( r =0.28, P < 0.0005) and HDL cholesterol concentration ( r = − 0.272, P < 0.0005) were weakly associated with apo B-48 concentration. In subjects with MetS, the association of apo B-48 with triglyceride and non-HDL cholesterol was enhanced, but neither were robust markers of elevated apo B-48 in MetS (r = 0.618 and r = 0.595 respectively). There was no association between apo B-48 and HDL cholesterol in subjects with MetS. Conclusion: This study demonstrates a substantial accumulation of pro-atherogenic remnants in subjects with MetS. We have shown that in a Caucasian cohort, the fasting plasma concentration of triglyceride or HDL/non-HDL cholesterol serves as poor surrogate markers of atherogenic chylomicron remnants. These findings suggest that subjects with MetS exhibit a chronic defect in chylomicron metabolism that is likely to contribute to their increased CV risk

Development and psychometric properties of a belief-based Physical Activity Questionnaire for Diabetic Patients (PAQ-DP)

<p>Abstract</p> <p>Background</p> <p>This study carried out to develop a scale for assessing diabetic patients' perceptions about physical activity and to test its psychometric properties (The Physical Activity Questionnaire for Diabetic Patients-PAQ-DP).</p> <p>Methods</p> <p>An item pool extracted from the Theory of Planned Behavior literature was generated. Then an expert panel evaluated the items by assessing content validity index and content validity ratio. Consequently exploratory factor analysis (EFA) was performed to indicate the scale constructs. In addition reliability analyses including internal consistency and test-retest analysis were carried out.</p> <p>Results</p> <p>In all a sample of 127 women with diabetes participated in the study. Twenty-two items were initially extracted from the literature. A six-factor solution (containing 19 items) emerged as a result of an exploratory factor analysis namely: instrumental attitude, subjective norm, perceived behavioral control, affective attitude, self-identity, and intention explaining 60.30% of the variance observed. Additional analyses indicated satisfactory results for internal consistency (Cronbach's alpha ranging from 0.54 to 0.8) and intraclass correlation coefficients (ranging from 0.40 to 0.92).</p> <p>Conclusions</p> <p>The Physical Activity Questionnaire for Diabetic Patients (PAQ-DP) is the first instrument that applies the Theory of Planned Behavior in its constructs. The findings indicated that the PAQ-DP is a reliable and valid measure for assessing physical activity perceptions and now is available and can be used in future studies.</p

Dynamic Landscapes, Emerging Territories

As a result of the pressing environmental and technological conditions dominant today, new frontiers for architectural production are emerging. Fueled by accelerated change and increased connectivity, these trajectories operate across multiple scales and domains. The evolving relationship between place, technology, and occupancy formulates a complex active structure that tends to have fluctuating levels of activity and impact. These conditions are giving way to hybridized settings where the interdependence of digital and analog is altering the very politics of place and identity. In response to the prevalence of amalgamated settings, the paradigm of “Dynamic Landscapes, Emerging Territories” is presented. Dynamic Landscapes have definitions and presence in multiple locations simultaneously, requiring new methods of documentation and assessment in order to conceive appropriate design responses. The paper uses the Syrian Refugee Crisis as a case study for deciphering the implications inherent in displacement in the context of dynamic landscapes. Furthermore, it presents an opportunity to think of new architectural trajectories rooted and driven by the animation of such sites. Inherently dynamic, forced displacement presents rich emerging territories where design carries significant impact and facilitates a tangible reassessment of a refugee’s narrative. Supported by robust information networks and active feedback loops, displaced landscapes as such can learn from their residents and inform their imminent futures specifically, as well as our collective human occupancy at large. Within constantly changing milieus, architecture’s premises and processes are being challenged to respond to fluctuating contexts and provide for transient occupancies. While some may see this as a loss of spatial agency when it comes to design, these conditions present an opportunity to think of new architectural trajectories that are rooted and driven by the dynamism of multilayered landscapes and new approaches towards practice

Abdominal obesity and low physical activity are associated with insulin resistance in overweight adolescents: a cross-sectional study

ABSTRACT: Background: Previous studies have assessed the metabolic changes and lifestyles associated with overweight adolescents. However, these associations are unclear amongst overweight adolescents who have already developed insulin resistance. This study assessed the associations between insulin resistance and anthropometric, metabolic, inflammatory, food consumption, and physical activity variables amongst overweight adolescents. Methods: This cross-sectional study divided adolescents (n = 120) between 10 and 18 years old into 3 groups: an overweight group with insulin resistance (O + IR), an overweight group without insulin resistance (O-IR), and a normal-weight control group (NW). Adolescents were matched across groups based on age, sex, pubertal maturation, and socioeconomic strata. Anthropometric, biochemical, physical activity, and food consumption variables were assessed. Insulin resistance was assessed using homeostatic model assessment (HOMA Calculator Version 2.2.2 from ©Diabetes Trials Unit, University of Oxford), and overweight status was assessed using body mass index according to World Health Organization (2007) references. A chi-square test was used to compare categorical variables. ANOVAs or Kruskal-Wallis tests were used for continuous variables. Multiple linear regression models were used to calculate the probability of the occurrence of insulin resistance based on the independent variables. Results: The risk of insulin resistance amongst overweight adolescents increases significantly when they reach a waist circumference > p95 (OR = 1.9, CIs = 1.3-2.7, p = 0.013) and watch 3 or more hours/day of television (OR = 1.7, CIs = 0.98-2.8, p = 0.033). Overweight status and insulin resistance were associated with higher levels of inflammation (hsCRP ≥1 mg/L) and cardiovascular risk according to arterial indices. With each cm increase in waist circumference, the HOMA index increased by 0.082; with each metabolic equivalent (MET) unit increase in physical activity, the HOMA index decreased by 0.026. Conclusions: Sedentary behaviour and a waist circumference > p90 amongst overweight adolescents were associated with insulin resistance, lipid profile alterations, and higher inflammatory states. A screening that includes body mass index, in waist circumference, and physical activity evaluations of adolescents might enable the early detection of these alterations