angiotensinogen and Weight-Loss

Topics: Angiotensinogen; Animals; Antihypertensive Agents; Clinical Trials as Topic; Diet, Sodium-Restricted; Humans; Hypertension; Mice; Mice, Knockout; Mice, Transgenic; Pharmacogenetics; Polymorphism, Genetic; Weight Loss

Obesity is a worldwide pandemic that causes a multitude of co-morbid conditions.However, there has been slow progress in understanding the basic pathophysiology that underlies co-morbid conditions associated with obesity. Recently, there has been intense interest in the role of inflammation in obesity. Using the inflammatory hypothesis, many of the mechanisms by which co-morbid conditions are associated with obesity are being elucidated.. We searched the literature and reviewed all relevant articles. We focused on hormones and cytokines that have been associated with other inflammatory conditions such as sepsis and systemic inflammatory response syndrome.. Angiotensinogen (AGT), transforming growth factor beta (TGFbeta), tumor necrosis factor alpha (TNFalpha), and interleukin six (IL-6) are all elevated in obesity and correlate with several markers of adipocyte mass. These mediators have detrimental effects on hypertension, diabetes, dyslipidemia, thromboembolic phenomena, infections, and cancer. Weight loss results in a reduction of inflammatory mediators and a diminution of the associated co-morbid conditions.. The success of weight loss surgery in treating the complications associated with obesity is most probably related to the reduction of inflammatory mediators. While some aspects of bariatric physiology remain unclear, there appears to be a strong association between obesity and inflammation, thereby rendering obesity a chronic inflammatory state. A clearer understanding of the physiology of obesity will allow physicians who treat the obese to develop better strategies to promote weight loss and improve the well-being of millions of individuals.

Topics: Acute-Phase Proteins; Adipose Tissue; Angiotensin II; Angiotensinogen; C-Reactive Protein; Humans; Inflammation; Insulin Resistance; Interleukin-6; Liver; Lymphotoxin-alpha; Morbidity; Obesity; Tumor Necrosis Factor-alpha; Weight Loss

Sleeve gastrectomy (SG) has been used as a multipurpose surgical procedure for the treatment of obesity.. The present study aimed to assess the effects of SG on the metabolic and inflammatory profile and renin-angiotensin system (RAS) expression in the white adipose tissue of male rats with obesity induced by a high-fat diet.. Male Wistar rats were treated with a standard diet or high-fat diet and submitted to SG or sham surgery. The glycemic and lipid profiles and gene expression of inflammatory markers and RAS components in adipose tissue were evaluated.. SG led to weight loss, decreased adiposity (p < 0.01) and a reduction in plasma glucose (p < 0.05), C-peptide (p < 0.05), insulin (p < 0.001) and total cholesterol (p < 0.05) levels. In addition, SG led to a decrease in the expression of tumor necrosis factor-alpha (TNF-α) (p < 0.01), interleukin- 6 (IL-6) (p < 0.001), angiotensinogen (AGT) (p < 0.001) and angiotensin converting enzyme (ACE) (p < 0.05) and increased the expression of angiotensin converting enzyme 2 (ACE2) (p < 0.05) in white adipose tissue. No statistically significant differences were observed for AT1 (p = 0.10) and Mas (p = 0.22) receptors.. This study showed that SG leads to weight loss and improves metabolic parameters. Changes in the expression of RAS components and of inflammatory molecules in adipose tissue seem to play a role the before beneficial effects of the SG.

Topics: Adipose Tissue; Angiotensinogen; Animals; Diet, High-Fat; Gastrectomy; Humans; Interleukins; Male; Metabolome; Obesity; Peptidyl-Dipeptidase A; Rats, Wistar; Renin-Angiotensin System; Tumor Necrosis Factor-alpha; Weight Loss

Multiple reaction monitoring (MRM)-based mass spectrometric quantification of peptides and their corresponding proteins has been successfully applied for biomarker validation in serum. The option of multiplexing offers the chance to analyze various proteins in parallel, which is especially important in obesity research. Here, biomarkers that reflect multiple comorbidities and allow monitoring of therapy outcomes are required. Besides the suitability of established MRM assays for serum protein quantification, it is also feasible for analysis of tissues secreting the markers of interest. Surprisingly, studies comparing MRM data sets with established methods are rare, and therefore the biological and clinical value of most analytes remains questionable. A MRM method using nano-UPLC-MS/MS for the quantification of obesity related surrogate markers for several comorbidities in serum, plasma, visceral and subcutaneous adipose tissue was established. Proteotypic peptides for complement C3, adiponectin, angiotensinogen, and plasma retinol binding protein (RBP4) were quantified using isotopic dilution analysis and compared to the standard ELISA method. MRM method variabilities were mainly below 10%. The comparison with other MS-based approaches showed a good correlation. However, large differences in absolute quantification for complement C3 and adiponectin were obtained compared to ELISA, while less marked differences were observed for angiotensinogen and RBP4. The verification of MRM in obesity was performed to discriminate first lean and obese phenotype and second to monitor excessive weight loss after gastric bypass surgery in a seven-month follow-up. The presented MRM assay was able to discriminate obese phenotype from lean and monitor weight loss related changes of surrogate markers. However, inclusion of additional biomarkers was necessary to interpret the MRM data on obesity phenotype properly. In summary, the development of disease-related MRMs should include a step of matching the MRM data with clinically approved standard methods and defining reference values in well-sized representative age, gender, and disease-matched cohorts.

Topics: Adiponectin; Adipose Tissue; Adult; Aged; Angiotensinogen; Biomarkers; Blood Proteins; Chromatography, High Pressure Liquid; Comorbidity; Complement C3; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Obesity; Peptides; Proteomics; Reproducibility of Results; Retinol-Binding Proteins, Plasma; Tandem Mass Spectrometry; Weight Loss

The mechanisms underlying the association of the increased albumin excretion rate (AER) with adiposity have yet to be clarified. We therefore investigated (1) the predictors of AER after 3 months of lifestyle intervention in a large cohort of nondiabetic obese women and (2) the relationships between AER and the adipose tissue gene expression of adipokines linked to inflammation and insulin resistance.. A total of 269 obese nondiabetic women (age 49.9+/-13.1 years, body mass index (BMI) 36.8+/-4.6 kg m(-2)) participated in this program. Measurements used were anthropometrics parameters, blood pressure, oral glucose tolerance test, lipids, creatinine, AER, homeostasis model assessment of insulin resistance (HOMA-IR) and glomerular filtration rate at baseline and after 3 months of lifestyle intervention. At baseline, in a subgroup of 34 women, subcutaneous adipose tissue biopsy was carried out for the analysis of mRNA expression levels of adiponectin, suppressor of cytokine signaling 3 (SOCS-3), tumor necrosis factor alpha (TNF-alpha), pentraxine 3 (PTX-3), angiotensinogen and angiotensin-converting enzyme, and a blood sample was also taken from this group for the measurement of circulating adiponectin, interleukin-6, TNF-alpha and PTX-3. Microalbuminuria was defined as albumin/creatinine ratio >or=3.5 mg mmol(-1). Real-time PCR was used to quantify mRNA.. Six percent of obese women had microalbuminuria. When dividing the whole cohort into three groups according to AER changes (decrease, stability and increase), we noted that 2 h glucose, insulin and HOMA-IR significantly decreased (P<0.05 for all) only in women who had a decrease in AER, whereas BMI and waist circumference significantly decreased in all the three groups (P<0.05). At baseline, higher AER was associated to significantly higher adipose tissue mRNA expression levels of SOCS-3 and PTX-3 (P<0.05) and to higher TNF-alpha and angiotensinogen expression.. In obese women, weight loss alone is not sufficient to induce the AER decrease that occurs only with a concomitant improvement in glucose homeostasis. The adipose tissue gene expression profile seems to favor the early renal impairment often seen in obese subjects.

Topics: Adiponectin; Albumins; Albuminuria; Angiotensinogen; Body Mass Index; C-Reactive Protein; Female; Gene Expression; Humans; Insulin Resistance; Middle Aged; Obesity; Peptidyl-Dipeptidase A; Predictive Value of Tests; Risk Reduction Behavior; Serum Amyloid P-Component; Subcutaneous Fat; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Tumor Necrosis Factor-alpha; Weight Loss

Topics: Angiotensinogen; Cross-Sectional Studies; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Life Style; Polymorphism, Genetic; Sodium Chloride, Dietary; Weight Loss

To investigate the relationship between angiotensinogen (AGT) Met235Thr polymorphism (M235T) and human obesity, because AGT is regarded as one of the cytokines produced from adipocytes and serum AGT concentrations are reported to be positively correlated with body mass index. One hundred and twenty obese Japanese women (age, 58.8+/-9.4 years; body mass index, 32.2+/-4.9 kg/m(2)) were enrolled. Angiotensinogen genotypes were determined with a fluorescent allele-specific DNA primer assay system. Subjects were divided into M/M, M/T, and T/T groups. Control subjects comprised 146 healthy age-matched women. Clinical characteristics and the effects of diet and exercise therapy for 6 months were compared among the 3 genotypes. The genotype frequencies of AGT M235T polymorphism were in accordance with the Hardy-Weinberg equation (obese: M/M, 6.7%; M/T, 27.5%; T/T, 65.8%; control: M/M, 6.8%; M/T, 21.2%; T/T, 71.9%). The frequency of the T allele did not differ between obese and control subjects (0.80 vs 0.83). As the number of obese women with M/M genotype was only 8, comparisons of the characteristics and outcomes of weight reduction therapy were performed only between subjects with M/T genotype and T/T genotype. In the T/T group, % body fat and waist circumference at baseline were significantly greater than in the M/T group (36.3%+/-4.8% vs 33.8%+/-4.7%, P=.0105; 107.9+/-10.9 vs 102.6+/-7.9 cm, P=.0428, respectively). Before the weight reduction therapy, significantly higher insulin and higher homeostasis model assessment (HOMA-R) were demonstrated in the T/T group than in the M/T group (9.1+/-5.5 microU/mL vs 5.9+/-4.4 microU/mL, P=.0056; 2.3+/-1.4 vs 1.6+/-1.3, P=.0252, respectively). Both systolic and diastolic blood pressure at baseline in the T/T group tended to be higher than those in the M/T group, but the differences were not significant. No genotype-dependent difference in energy expenditure or outcome of weight reduction therapy was observed with respect to AGT M235T polymorphism. After the diet and exercise therapy, the blood pressure in the T/T group tended to be higher than that in the M/T group, but the difference was not significant. We demonstrated that the T/T genotype of the AGT M235T gene polymorphism was positively related to visceral obesity and hyperinsulinemia in obese Japanese women. Blood pressure did not show genotype-specific differences before or after the treatment. Further studies of the association between obesity and this gene pol

Topics: Aged; Amino Acid Substitution; Angiotensinogen; Body Fat Distribution; Case-Control Studies; Diet Therapy; Exercise Therapy; Female; Genotype; Humans; Insulin Resistance; Middle Aged; Obesity; Polymorphism, Genetic; Weight Loss

The renin-angiotensin-aldosterone system has been causally implicated in obesity-associated hypertension. We studied the influence of obesity and weight reduction on the circulating and adipose tissue renin-angiotensin-aldosterone system in menopausal women. Blood samples were analyzed for angiotensinogen, renin, aldosterone, angiotensin-converting enzyme activity, and angiotensin II. In adipose tissue biopsy samples, we analyzed angiotensinogen, renin, renin-receptor, angiotensin-converting enzyme, and angiotensin II type-1 receptor gene expression. Obese women (n=19) had higher circulating angiotensinogen, renin, aldosterone, and angiotensin-converting enzyme than lean women (n=19), and lower angiotensinogen gene expression in adipose tissue. Seventeen women successfully participated in a weight reduction protocol over 13 weeks to reduce daily caloric intake by 600 kcal. Body weight was reduced by -5%, as were angiotensinogen levels by -27%, renin by -43%, aldosterone by -31%, angiotensin-converting enzyme activity by -12%, and angiotensinogen expression by -20% in adipose tissue (all P<0.05). The plasma angiotensinogen decrease was highly correlated with the waist circumference decline (r=0.74; P<0.001). Weight and renin-angiotensin-aldosterone system reductions were accompanied by a -7-mm Hg reduced systolic ambulatory blood pressure. These data suggest that a 5% reduction in body weight can lead to a meaningfully reduced renin-angiotensin-aldosterone system in plasma and adipose tissue, which may contribute to the reduced blood pressure.

Topics: Adipose Tissue; Aldosterone; Angiotensinogen; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Middle Aged; Obesity; Peptidyl-Dipeptidase A; Renin; Renin-Angiotensin System; Weight Loss

A number of recent studies have demonstrated a protective effect of renin-angiotensin system (RAS) antagonism against immune mediated diseases such as myocarditis, chronic allograft rejection, and antiglomerular basement membrane nephritis. To our knowledge, there has been no report on the immunological contribution of the RAS in colonic tissue.. We evaluated the direct effect of angiotensin II (AII) on the pathogenesis of immune mediated colitis using angiotensinogen deficient homozygous (Atg-/-) mice.. 2,4,6-Trinitrobenzene sulphonic acid (TNBS) colitis was induced in Atg-/- and wild-type (Atg+/+) mice.. Levels of proinflammatory cytokines in the colon were determined by enzyme linked immunosorbent assay. Histological analysis was performed simultaneously.. Although Atg-/- mice developed colitis, the degree was much milder than that in Atg+/+ mice (p<0.05). Colonic cytokine analysis showed that the production of proinflammatory cytokines (interleukin (IL)-1beta, interferon gamma (IFN-gamma)) was impaired in Atg-/- mice. Furthermore, expression of cytokines such as IL-4 and IL-10 in the colon was predominant in Atg-/- compared with Atg+/+ mice after TNBS instillation (p<0.005, p<0.01, respectively). Similarly, subcutaneous infusion of losartan suppressed colitis (p<0.05) and the production of proinflammatory cytokines (IL-1beta, IFN-gamma). These results indicate that the RAS is directly involved in the pathogenesis of TNBS colitis through regulation of proinflammatory and anti-inflammatory cytokines in the colon.. This study revealed that the RAS is involved in the immune system in the colon. Antagonism of the RAS is a potential prophylactic strategy for the treatment of human inflammatory bowel disease.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensinogen; Animals; Colitis; Colon; Cytokines; Immunity, Mucosal; Intestinal Mucosa; Losartan; Male; Mice; Mice, Inbred ICR; Mice, Knockout; Renin-Angiotensin System; Trinitrobenzenesulfonic Acid; Weight Loss