Insulin up-regulates natriuretic peptide clearance receptor expression in the subcutaneous fat depot in obese subjects: a missing link between CVD risk and central obesity?

2012 ◽  
Vol 7 (S 01) ◽  
Author(s):  
O Pivovarova ◽  
Ö Gögebakan ◽  
N Klöting ◽  
A Ernst ◽  
MO Weickert ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Central Obesity ◽  
Subcutaneous Fat ◽  
Receptor Expression ◽  
Cvd Risk ◽  
Missing Link ◽  
Obese Subjects ◽  
Clearance Receptor ◽  
Fat Depot

Evidence for functional ANP receptors in cultured alveolar type II cells

1998 ◽  
Vol 274 (2) ◽  
pp. L244-L251 ◽  
Author(s):  
Pierre-Louis Tharaux ◽  
Jean-Claude Dussaule ◽  
Sylvianne Couette ◽  
Christine Clerici
Keyword(s):  
Natriuretic Peptide ◽  
Guanylate Cyclase ◽  
Competitive Inhibition ◽  
Receptor Expression ◽  
Na Channel ◽  
Alveolar Type ◽  
Type Ii ◽  
Basolateral Side ◽  
Clearance Receptor ◽  
Anp Receptors

Because atrial natriuretic peptide (ANP) is considered to play a role in lung physiology and pathology, our aim was to characterize natriuretic peptide receptors in cultured rat alveolar type II (ATII) cells. Guanylate cyclase A- and B-receptor but not clearance-receptor mRNAs were detected by reverse transcription-polymerase chain reaction. The absence of clearance-receptor expression in ATII cells was confirmed by competitive inhibition of ANP binding; ANP (0.1–100 nM) decreased the binding of 125I-ANP, whereas C-ANP-(4—23), a specific ligand of clearance receptors, was ineffective. ANP induced a dose-dependent increase in guanosine 3′,5′-cyclic monophosphate (cGMP) production, with a threshold of 0.1 nM, whereas the response to C-type natriuretic peptide was weak and was observed only at high concentrations (100 nM). In ATII cells cultured on filters, 1) ANP receptors were present on both the apical and basolateral surfaces and 2) cGMP egression was polarized, as indicated by the greater ANP-induced cGMP accumulation in the basolateral medium, and was partially inhibited by probenecid, an organic acid transport inhibitor. Influx studies demonstrated that ANP decreased the amiloride-sensitive component of22Na influx but did not change ouabain-sensitive 86Rb influx. In conclusion, ATII cells behave as a target for ANP. ANP activation of guanylate cyclase A receptors produces cGMP, which is preferentially extruded on the basolateral side of the cells and inhibits the amiloride-sensitive Na-channel activity.

scholarly journals Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway

2016 ◽  
Vol 311 (1) ◽  
pp. R104-R114 ◽  
Author(s):  
M. Bordicchia ◽  
M. Ceresiani ◽  
M. Pavani ◽  
D. Minardi ◽  
M. Polito ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Natriuretic Peptide ◽  
Receptor Expression ◽  
Human Adipocytes ◽  
Very Low Calorie Diet ◽  
Renal Surgery ◽  
Functional Link ◽  
Insulin Effect ◽  
Low Glucose ◽  
Clearance Receptor

Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes.

Postprandial dyslipidemia in men with visceral obesity: an effect of reduced LDL receptor expression?

2001 ◽  
Vol 281 (3) ◽  
pp. E626-E632 ◽  
Author(s):  
John C. L. Mamo ◽  
Gerald F. Watts ◽  
P. Hugh R. Barrett ◽  
Darrin Smith ◽  
Anthony P. James ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Hydrolytic Enzyme ◽  
Ldl Receptor ◽  
Surrogate Marker ◽  
Visceral Obesity ◽  
Receptor Expression ◽  
Cell Protein ◽  
Insulin Resistant ◽  
Postprandial Triglyceride ◽  
Obese Subjects

Postprandial lipemia after an oral fat challenge was studied in middle-aged men with visceral obesity. The two groups had similar plasma cholesterol levels, but obese subjects had higher levels of plasma triglyceride and reduced amounts of high-density cholesterol. Fasting plasma insulin was fourfold greater in obese subjects because of concomitant insulin resistance, with a calculated HOMA score of 3.1 ± 0.6 vs. 0.8 ± 0.2, respectively. Plasma apolipoprotein B48(apoB48) and retinyl palmitate (RP) after an oral fat challenge were used to monitor chylomicron metabolism. Compared with lean subjects, the fasting concentration of apoB48 was more than twofold greater in obese individuals, suggestive of an accumulation of posthydrolyzed particles. After the oral lipid load, the incremental areas under the apoB48 and RP curves (IAUC) were both significantly greater in obese subjects (apoB48: 97 ± 17 vs. 44 ± 12 μg · ml−1 · h; RP: 3,120 ± 511 vs. 1,308 ± 177 U · ml−1 · h, respectively). A delay in the conversion of chylomicrons to remnants probably contributed to postprandial dyslipidemia in viscerally obese subjects. The triglyceride IAUC was 68% greater in obese subjects (4.7 ± 0.6 vs. 2.8 ± 0.8 mM · h, P< 0.06). Moreover, peak postprandial triglyceride was delayed by ∼2 h in obese subjects. The reduction in triglyceride lipolysis in vivo did not appear to reflect changes in hydrolytic enzyme activities. Postheparin plasma lipase rates were found to be similar for lean and obese subjects. In this study, low-density lipoprotein (LDL) receptor expression on monunuclear cells was used as a surrogate marker of hepatic activity. We found that, in obese subjects, the binding of LDL was reduced by one-half compared with lean controls (70.9 ± 15.07 vs. 38.9 ± 4.6 ng LDL bound/μg cell protein, P = 0.02). Because the LDL receptor is involved in the removal of proatherogenic chylomicron remnants, we suggest that the hepatic clearance of these particles might be compromised in insulin-resistant obese subjects. Premature and accelerated atherogenesis in viscerally obese, insulin-resistant subjects may in part reflect delayed clearance of postprandial lipoprotein remnants.

scholarly journals Metabolic Syndrome in Italian Obese Children and Adolescents: Stronger Association with Central Fat Depot than with Insulin Sensitivity and Birth Weight

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Claudia Brufani ◽  
Danilo Fintini ◽  
Ugo Giordano ◽  
Alberto Enrico Tozzi ◽  
Fabrizio Barbetti ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Low Birth Weight ◽  
Children And Adolescents ◽  
Central Obesity ◽  
Obese Children ◽  
Obesity Index ◽  
Central Fat ◽  
Fat Depot

Aim. To evaluate whether body fat distribution, birth weight, and family history for diabetes (FHD) were associated with metabolic syndrome (MetS) in children and adolescents.Methods. A total of 439 Italian obese children and adolescents (5–18 years) were enrolled. Subjects were divided into 2 groups: prepubertal and pubertal. MetS was diagnosed according to the adapted National Cholesterol Education Program criteria. Birth weight percentile, central obesity index (measured by dual-energy X-ray absorptiometry), insulin sensitivity (ISI), and disposition index were evaluated. Multivariate logistic regression models were used to determine variables associated with MetS.Results. The prevalence of MetS was 17%, with higher percentage in adolescents than in children (21 versus 12%). In the overall population, central obesity index was a stronger predictor of MetS than insulin sensitivity and low birth weight. When the two groups were considered, central fat depot remained the strongest predictor of MetS, with ISI similarly influencing the probability of MetS in the two groups and birth weight being negatively associated to MetS only in pubertal individuals. Neither FHD nor degree of fatness was a significant predictor of MetS.Conclusion. Simple clinical parameters like increased abdominal adiposity and low birth weight could be useful tools to identify European obese adolescents at risk for metabolic complications.

scholarly journals Body Fat Percentage, Waist Circumference and Body Mass Index are Correlated with Nitric Oxide Levels in Young Adults with Central Obesity

2021 ◽  
Vol 5 (1) ◽  
pp. 1
Author(s):  
Feriyandi Nauli ◽  
Nurhasanah Nurhasanah ◽  
Endang Mahati ◽  
Udin Bahrudin
Keyword(s):  
Nitric Oxide ◽  
Body Mass Index ◽  
Young Adults ◽  
Waist Circumference ◽  
Body Mass ◽  
Body Fat ◽  
Central Obesity ◽  
Subcutaneous Fat ◽  
Body Fat Percentage ◽  
Fat Percentage

Background: Central obesity stands for the corner-stone of cardio-metabolic health, while nitric oxide (NO) is a major regulator of cardiovascular function. To day, the correlation between serum NO metabolites nitrate/nitrite and the obesity components in young adults remains elusive. Thus, this current study was conducted to know the correlation between serum NO metabolites levels and body fat percentage, waist circumference (WC) as well as body mass index (BMI) in young adults with central obesity.Materials and Methods: A cross-sectional study was conducted in Riau, Indonesia, involving 79 young adults aged 18-25 years, composing of 39 and 40 subjects with and without central obesity, respectively. Anthropometric measurements were performed to assess WC and BMI. Body fat percentage was measured using bioelectrical impedance analysis and serum NO metabolites levels were assessed using Griess methods.Results: Levels of serum NO metabolites were significant higher in the subjects with central obesity (168.41±12.64 μmol/L) than that of normal subjects (70.57±44.99 μmol/L, p<0.001), but the levels were no significant different between male and female subjects. Serum NO metabolites levels were strongly correlated with total body fat (r=0.618, p<0.001), visceral fat (r=0.733, p<0.001), subcutaneous fat (r=0.547, p<0.001), WC (r=0.717, p<0.001) and BMI (r=0.788, p<0.001).Conclusions: For young adults in Riau, Indonesia, levels of serum NO metabolites are higher in the central obesity group than that of the normal. In this population, body fat percentage, waist circumference and body mass index are correlated with serum nitric oxide metabolites levels.Keywords: nitric oxide, body fat percentage, young adults, central obesity

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