The Indonesian Biomedical Journal

Number 1, 2011

4-17
MicroRNAs in Obesity, Metabolic Syndrome and Diabetes Mellitus

Authors: Anna Meiliana, Andi Wijaya

Abstract

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Number of views: 319

BACKGROUND: MicroRNAs (miRNAs) are small regulatory RNAs that play important roles in development of diseases. Several studies have provided evidences showing that miRNAs affect pathways that are fundamental for metabolic control in adipocyte and skeletal muscle differentiations. Some miRNAs have been implicated in lipid, amino acid, and glucose homeostasis. This leads to the possibility that miRNAs may contribute to common metabolic diseases and point to novel therapeutic opportunities based on targeting of miRNAs. CONTENT: miRNAs have been recognized as a class of epigenetic regulators of metabolism and energy homeostasis, primarily because the simultaneous regulation of a large number of target genes can be accomplished by a single miRNA. Emerging evidences suggest that miRNAs play a key role in the pathological development of obesity by affecting adipocyte differentiation. miRNAs have been implicated as novel protagonists in the pathogenesis of Diabetes Mellitus (DM), regulation of insulin production, secretion and action. They also appear to play a role in the development of diabetic complications such as nephropathy and cardiac hypertrophy. SUMMARY: Involvement of miRNAs in glucose and lipid metabolism has provided strong evidences to confirm their roles as key players in regulation of complex metabolic pathways. Additionally, it indicates potential outlook for novel therapeutic strategies in the management of obesity, metabolic syndrome and DM. Further research in this field is needed to ascertain the full potential of miRNAs as novel metabolic biomarkers and potent therapeutic agents against obesity and its metabolic disorders.

18-36
Microparticles Novel Mechanisms of Intracellular Communication: Implication in Health and Disease

Authors: Anna Meiliana, Andi Wijaya

Abstract

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Number of views: 324

BACKGROUND: The prevailing view that eukaryotic cells are restrained from intercellular exchange of genetic information has been challenged by recent reports on nanotubes, exosomes, apoptotic bodies, and nucleic acid—binding peptides that provide novel pathways for cell—cell communication, with implications in health and disease. CONTENT: Microparticles (MPs) are a heterogeneous population of small plasma membrane structures that serve as important signaling structures between cells. MPs are composed of a phospholipid bilayer that exposes transmembrane proteins and receptors and encloses cytosolic components such as enzymes, transcription factors, and mRNA derived from their parent cells. Growing evidence suggests that MPs regulate inflammation, stimulate coagulation, affect vascular functions and apoptosis, and can also play a role in cell proliferation or differentiation. MPs circulate in the bloodstream, can be detected in the peripheral blood, and may originate from different vascular cell types (eg, platelets, monocytes, endothelial cells, red blood cells, and granulocytes). SUMMARY: Cells of various types release small membrane vesicles called MP on their activation, as well as during the process of apoptosis. The properties and roles of MP generated in different contexts are diverse and are determined by their parent cell and the pathway of their generation, which affects their content. MP are involved in multiple cellular functions, including immunomodulation, inflammation, coagulation, and intercellular communication. MPs are able to deliver molecular signals in the form of lipids, proteins, nucleic acids, or functional trans-membrane proteins from the parent cell to distantly located targets. From a clinical point of view, MP may serve as biomarkers for disease status and may be found useful for developing novel therapeutic strategies.

37-42
Correlation of Urine Albumin/Creatinine Ratio (UACR), High Sensitivity C-Reactive Protein (hsCRP) and N-Terminal Pro Brain Natriuretic Peptide (NT-proBNP) with Atherosclerosis (OxLDL) in Centrally Obese Men

Authors: Nancy Pakpahan, Mansyur Arif, Ilhamjaya Patellongi

Abstract

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Number of views: 354

BACKGROUND: Obesity is closely associated with atherosclerosis risk and cardiovascular disease. Novel cardiovascular risk biomarkers such as Urine Albumin/Creatinine Ratio (UACR), High Sensitivity C-Reactive Protein (hsCRP) and N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) have been observed to predict cardiovascular disease in the general population. The aim of this study was to observe the correlation of UACR, hsCRP and NT-proBNP with atherosclerosis (OxLDL) in centrally obese men. METHODS: The study was observational with a cross sectional design done on 76 male subjects aged 30–50 years with central obesity and mean of age of 37 years. Urine albumin was determined by PEG enhanced immunoturbidimetric assay, urine creatinine by Jaffe without deproteinase, hsCRP by chemiluminescent immunometric assay, NT-proBNP by electrochemiluminescence (ECLIA) and OxLDL by ELISA. RESULTS: There was significant correlation between hsCRP and OxLDL (r=0.230, p=0.046). There was no significant correlation between UACR and OxLDL (r=-0.138, p=0.236), neither between Log NT-proBNP and OxLDL (r=-0.173, p=0.136). CONCLUSIONS: Atherosclerosis was significantly correlated with hsCRP (low grade inflammation).

43-50
Correlation between Interleukin-6 (IL-6), High Sensitivity C-Reactive Protein (hsCRP), Endothelin-1 (ET-1), Asymmetric Dimethylarginine (ADMA) and Insulin Resistance (HOMA-IR) in Central Obese Men

Authors: Andri Hidayat, Andi Wijaya, Harun Alrasyid

Abstract

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Number of views: 337

BACKGROUND: Many studies have shown that obesity was closely related to insulin resistance via several pathways such as inflammation, oxidative stress, lipolysis, and endothelial dysfunction. This study was carried out to observe the correlation between inflammation (IL-6 and hsCRP), lipolysis process (ET-1), and endothelial dysfunction (ADMA) and insulin resistance (HOMA-IR) in centrally obese men. METHODS: This was a cross sectional study on 62 male subjects aged 30–60 years old with waist circumference (WC) >90 cm. IL-6, ET-1 and ADMA levels were measured using ELISA method, while hsCRP and insulin were measured using chemiluminescence method. All blood testings were conducted in Prodia Clinical Laboratory. RESULTS: The results showed that WC was significantly correlated with hsCRP (r=0.294, p=0.022 ), ET-1 (r=0.257, p=0.047 ) and ADMA (r=0.338, p=0.009). We also found a significant correlation between hsCRP with HOMA-IR (r=0.324, p=0.021), ADMA with HOMA-IR (r=0.280, p=0.045), and IL-6 with hsCRP (r=0.437, p=0.003). CONCLUSIONS: hsCRP and ADMA have significant correlation with HOMA-IR in centrally obese men. HOMA-IR significantly increases in subjects with ADMA above median and either IL-6 or hsCRP above median, as compared to those in the other groups. Inflammation and endothelial dysfunction are important causal pathways of insulin resistance state in centrally obese men.

51-6
Lipoprotein (a) and Lipoprotein-associated Phospholipase A2 as Atherosclerosis Risk Factors (oxLDL) in Men with Central Obesity

Authors: Nelly Sari, Andi Wijaya, Ilhamjaya Patellongi

Abstract

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Number of views: 331

BACKGROUND: The increasing prevalence of obesity in Indonesia triggers a lot of research interest to overcome it. Obesity has a very important role as atherosclerosis and cardiovascular risk factors. The presence of oxidized LDL (oxLDL) on the vascular wall is a marker of atherosclerosis. The increase of Lipoprotein(a) (Lp(a)) and Lipoprotein associate phospholipase A2 (LpPLA2) occurs in patients with coronary artery disease (CAD), myocardial infarction, and unstable angina. It is well accepted that obesity is closely related to atherosclerosis and cardiovascular risk factors. However, correlation between Lp(a), LpPLA2 and oxLDL in central obesity has not yet been investigated. The aim of this study was to observing the correlation between Lp(a), LpPLA2 and oxLDL in early central obesity. METHODS: An observational study with cross-sectional design on 76 men with central obesity, aged 30-67 years, was conducted. Central obesity was characterized by waist circumference >90 cm. Test of Lp(a) was performed by turbidimetric method and that of LpPLA2 was performed by sandwich enzyme immunoassay. Test of oxLDL was performed by ELISA. All statistical analyses were carried out using SPSS for Windows v.11.5 at a significance level of p<0.05. The Pearson and Spearman’s Rho correlation coefficient was used to assess the correlation between Lp(a), LpPLA2 and oxLDL. Obese men with acute inflammation (hsCRP > 10 mg/L), renal failure (Creatinine >1.5 mg/dL) and consumed antiinflammation were excluded from this study. RESULTS: The concentration of LpPLA2 had a linear correlation (r=-0.340, p=0.003) with the increase of oxLDL concentration. However, concentration of Lp(a) did not have linear correlation (r = 0.025) with increase of oxLDL concentration. This finding indicates that concentration of LpPLA2 had a negative correlation with increase of concentration of oxLDL. In addition, Lp(a) appears not to correlate with oxLDL significantly. CONCLUSION: The study showed there was a significant correlation between concentration of LpPLA2 and concentration of oxLDL in men with central obesity. Higher concentration of LpPLA2 correlated with lower concentration of oxLDL.

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The Correlation of Gamma-Glutamyl Transferase (γ-GT), Glutathione Peroxidase (GPx) and Total Antioxidant Status (TAS) with Inflammatory Marker in Individuals with Metabolic Syndrome

Authors: Susana Gunawan, Anwar Santoso, Andi Wijaya

Abstract

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Number of views: 320

BACKGROUND: γ-GT is known as a primary enzyme that constituent extracellular glutathione catabolism. Various researches have proven that an increase in γ-GT concentration is related to oxidative stress and to components of metabolic syndrome. With individuals having metabolic syndrome as research subjects, our objective is to find the correlation of γ-GT, GPx and SAT. METHODS: This was a cross sectional study done on 36 subjects with metabolic syndrome who met the IDF 2005 criteria. Statistical analysis was carried out using SPSS for Windows ver.11.5 with a significance level of p<0.05. The correlation among biomarkers were assessed using Spearman’s Rho test. RESULTS: γ-GT concentration was correlated negatively with GPx concentration (r=-0.411, p=0.014), but correlated positively with hs-CRP concentration (r=0.385, p=0.022). The increase of γ-GT concentration had a potential risk 8.5 times higher than the increase of hs-CRP concentration, which proved to be more dominant in comparison to its risk to γ-GT/GPx or γ-GT/SAT ratios (p<0.05). CONCLUSIONS: An increase in γ-GT concentration characterizes signs of oxidative stress syndrome and of inflammation in individuals with metabolic syndrome.

64-9
Association among Soluble Tumor Necrosis Factor Receptor I, Matrix Metalloproteinase-9, Procollagen C-terminal Propeptide type I, and N-Terminal proBrain Natriuretic Peptide in Heart Failure

Authors: Mona Yolanda, Marsetio Donosepoetro, Anwar Santoso, Mansyur Arif

Abstract

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Number of views: 320

BACKGROUND: Heart failure (HF) is associated with an increased expression of proinflammatory cytokines, especially soluble tumor necrosis factor receptor I (sTNFR I), but the underlying mechanism to the relationship between sTNFR I activation and the progression of HF is not yet fully understood. This study aims to see the association between sTNFR I, MMP-9, PICP, and NT-proBNP in the progression of HF. METHODS: This was a cross sectional study which recruited 45 subjects with HF confirmed by echocardiography and NT-proBNP. Concentration sTNFR I, MMP-9, and PICP were measured using ELISA method, whereas NT-proBNP concentration was measured using ECLIA method. Univariate linear regression analysis, path analysis and General Linear Model were used to determine which parameters played the most significant role in HF. RESULTS: Results of the univariate linear regression and path analysis showed there was a linear relationship between sTNFR I with MMP-9, with R square of 25.8% (p=0.00; r=0.508), R square sTNFRI and MMP-9 with PICP was 14.4% (p=0.038; r=0.379) and R square MMP-9 and PICP with NT-proBNP was 39.6% (p=0.00; r=0.629). From the General Linear Model we found that the important predictor for HF was through MMP-9 and PICP. CONCLUSION: sTNFR I as a proinflammatory factor is one of the factors involved in the heart failure as seen by NT-proBNP through activation of brosis (PICP) and remodeling factor (MMP-9).