الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Obesity has become a pandemic health problem that along with overweight, affected 42% of the world population in 2014. Obesity is an energy balance disorder in which nutrient intake chronically exceeds energy expenditure, resulting in excessive WAT accumulation. Central obesity is frequently associated with insulin resistance and both form the basis of the pathophysiology of dyslipidemia, glucose intolerance, and hypertension in metabolic syndrome.
Secreted protein acidic and rich in cysteine (SPARC) is the first extracellular regulatory glycoprotein described in WAT. SPARC facilitates interactions between cell and ECM impacting upon cell signaling, adhesion, proliferation, migration, and survival. It is expressed in most human tissues with highest expression in subcutaneous and visceral adipose tissue.
In obesity, secretion of SPARC by adipocytes is increased where it inhibits adipogenesis during states of positive energy balance. Previous human studies showed that serum SPARC levels were positively associated with markers of adiposity and insulin resistance in non-diabetic obese subjects. Moreover AT-SPARC expression was found to be regulated by caloric intake and weight change in humans.
Accumulating evidence suggested that SPARC is implicated in pathogenesis of obesity and Insulin resistance. The influence of SPARC in insulin resistance may arise from its role in the regulation of collagen assembly and ECM remodeling. The increased AT-SPARC expression in obesity may further promote ECM fibrosis which in turn impairs adipocyte differentiation and AT expansion. Fibrosis is characterized by increased deposition of collagen in ECM due to imbalance between excess synthesis and impaired degradation. In obese subjects, fibrosis was described in WAT depots and was associated with obesity comorbidities.
In the present study, we assessed SPARC levels in serum, subcutaneous and visceral adipose tissues. We quantified total collagen content in both AT depots. We also tested the hypothesis that AT fibrosis is the underlying mechanism that links SPARC to peripheral insulin resistance in human obesity.
A cross-sectional study was conducted on 40 sedentary non diabetic men undergoing elective abdominal surgeries in the general Surgery department of Alexandria Main University Hospital and at the Department of Clinical Surgery, Medical Research Institute, University of Alexandria.
Participants were classified by BMI cut-offs into group I normal-weight
(n = 20), and group II overweight/obese (OW/OB; BMI ≥25; n = 20). Subcutaneous (n = 40) and visceral fat (n = 36) samples were taken during surgeries. Serum and AT SPARC levels were assayed by ELISA. Total collagen content was quantified by measuring hydroxyproline concentrations in AT samples by calorimetric methods. These parameters were correlated with obesity indicators, fasting serum glucose, insulin & insulin resistance. SAT and VAT biopsies were stained with H&E stain and Trichrome stains to demonstrate collagen fibers. Morphometric analysis was performed on Trichrome stained photomicrographs to calculate collagen accumulation % in AT samples.
Results of the current work revealed that, overweight and obese group had higher measures of central adiposity (WC, WHR and WHtR) than the normal weight group. Moreover, fasting insulin and HOMA-IR were significantly higher in overweight and obese subjects compared to those having normal weights. However, blood pressure and lipid profile were not significantly different between the two groups. In addition, overweight and obese subgroup had higher levels of SPARC in Serum, subcutaneous and visceral fat than in normal weight group. The elevation of hydroxyproline content in subcutaneous and visceral fat of overweight and obese group was modest and did not reach significance. However, percentage of collagen accumulation was more pronounced in obese than in lean men. Furthermore, microscopic examination depicted more dense arrangement of thicker collagen fibers in between adipocytes in SAT and VAT of obese versus lean subjects.
Serum SPARC showed positive correlation with markers of insulin resistance and obesity indicators such as (BMI, Fat%, WC, and WHtR). In both AT depots, SPARC protein concentration and hydroxyproline content were strongly and positively correlated. Despite the higher SPARC and hydroxyproline levels in SAT than in VAT, they didn’t correlate with markers of insulin resistance whereas VAT-SPARC levels and omental fibrosis were positively associated with fasting serum insulin levels.
Based on the above data, omental fibrosis could be a potential mechanistic link between increased VAT-SPARC synthesis and peripheral insulin resistance in moderately obese Egyptian men.