Atrial natriuretic peptide contributes to the physiological control of lipid mobilization in humans

Moro, Cédric; Crampes, F.; Sengenès, Coralie; Glisezinski, Isabelle de; Galitzky, Jean; Thalamas, Claire; Lafontan, Max; Berlan, Michel

doi:10.1096/fj.03-1086fje

Cited by 157 publications

(140 citation statements)

References 32 publications

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“…Both genes encode peptides that can be produced by adipose tissue, and that can influence adipogenesis and lipogenesis in an autocrine/paracrine manner; in addition, when released into the circulation, they may regulate BP. 25,[27][28][29] As such, either of the 2 genes may exert pleiotropic effects on adiposity and BP. Alternatively, the locus may include 2 closely linked genes that cosegregate within families, with one being involved in the regulation of adiposity and the other in the control of BP.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Scan for Linkage to Obesity-Associated Hypertension in French Canadians

et al. 2005

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Abstract-Essential hypertension is a heterogeneous disorder that is thought to develop because of several overlapping subsets of underlying mechanisms. One such causal pathway may involve pathophysiological alterations induced by obesity. In the present study, we examined whether investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, facilitates the search for its genes. Fifty-five extended families were selected on the basis of having Ն2 siblings affected by hypertension from a geographically remote French-Canadian population. Fifteen of these families showed a high prevalence (Ն70%) of obesity. Genome-wide scan using qualitative multipoint linkage analysis (GeneHunter 2.1; marker density Ͻ10 cM) was performed in the entire set of hypertensive families and the subset with high prevalence of obesity. In the scan involving all 55 families, the most significant loci (logarithm of odds [LOD] scoreϭ2.5) were identified on chromosomes 1 (D1S1597) and 11 (D11S1999). In the scan including only the subset of families with obesity-hypertension, the most significant locus (LOD scoreϭ3.1) was found on chromosome 1 in the same region as the scan involving all families (D1S1597). Genotyping additional markers increased the significance of this locus (LOD scoreϭ3.5) and refined its position (D1S2672). Several candidate genes of obesity-hypertension are located in close proximity; these include the tumor necrosis factor receptor 2 and atrial natriuretic peptide genes. These results suggest that investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, may facilitate the search for genes of this complex disorder. Key Words: hypertension, obesity Ⅲ genetics E ssential hypertension is a heterogeneous disorder that develops because of several overlapping subsets of pathophysiological mechanisms. Obesity is a leading risk factor for the disorder, and as such, may be a key element in one of these subsets. Prospective cohort investigations have demonstrated positive correlations between weight gain and blood pressure (BP) elevation. 1 For example, in the Framingham Study, it was estimated that for each 4.5 kg of weight gain, there is an associated increase in systolic BP of 4 mm Hg in both men and women. 2 Pathophysiological mechanisms linking the increases in adiposity to the elevations in BP are not very well understood. They may include alterations in renal handling of sodium and water, sympathetic nervous system activity, insulin sensitivity, and fatty acid metabolism, 3 with some of these alterations being induced by hormones, growth factors, and cytokines expressed by adipose tissue in response to its expansion.Hypertension and obesity are multifactorial traits determined by a complex interplay of genes and environments. 4 A number of genes contribute to the determination of each of these traits, and their actions are simple, additive, or more complex, characterized by phenomena such as epistasis and pleiotropy. Furthermore, hypertension and ...

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Scan for Linkage to Obesity-Associated Hypertension in French Canadians

et al. 2005

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“…15,53 During lipolysis, TAGs are broken down in a stepwise fashion to free fatty acids (FFA) and glycerol. In humans, lipolysis is modulated by the sympathetic nervous system, insulin and atrial natriuretic peptide (ANP), 54 and is markedly influenced by fat depot, sex and adiposity. 15 Catecholamines act through stimulatory beta 1 (ADRB1), beta 2 (ADRB2) and beta 3 (ADRB3) adrenoreceptors or inhibitory alpha 2 (ADRA2) adrenoreceptors.…”

Section: Pathways Controlling Lipid Storage In Adipocytesmentioning

confidence: 99%

Obesity and polymorphisms in genes regulating human adipose tissue

Dahlman

Arner

2007

Int J Obes

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Obesity is the result of an imbalance between food intake and energy expenditure resulting in the storing of energy as fat. Adipose tissue contains the largest store of energy in the body and plays important roles in regulating energy partitioning. Developments in genomics, in particular microarray-based expression profiling, have provided scientists with a number of new candidate genes whose expression in adipose tissue is regulated by obesity. Integrating expression profiles with genome-wide linkage and/or association analyses is a promising strategy to identify new genes underlying susceptibility to obesity. This article provides a comprehensive review of adipose-tissue-expressed genes implicated in predisposition to human obesity. The authors consider the following genes of particular interest: peroxisome proliferator-activated receptor gamma and, potentially, INSIG2 acting in adipogenesis; the adrenoreceptors beta 2 and 3, as well as hormone-sensitive lipase acting on lipolysis; uncoupling protein 2 acting in mitochondria energy expenditure; and among secreted molecules the cytokine tumor necrosis factor alpha and the hormone leptin. With the rapid development in genome research, we predict that additional alleles in genes regulating adipose tissue function will be established as risk factors for common obesity in the coming years. This has important implications for the prevention of obesity and may also offer new therapeutic targets.

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“…nondiabetic Japanese subjects; 21 NPPA has been found to play a noticeable role in the control of lipid mobilization 22 and may affect the course of nephropathy in inadequately controlled type 1 diabetes; 23 and ADRB2 has been associated with nocturnal asthma, obesity, and type 2 diabetes. 24 -27 Probably most significant is that inhibition of the renin-angiotensin system has been shown to be able to prevent diabetes.…”

Section: Guo Et Al Hypertension Genes Affect Insulin Resistancementioning

confidence: 99%

Hypertension Genes Are Genetic Markers for Insulin Sensitivity and Resistance

et al. 2005

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Abstract-Insulin resistance is a determinant of blood pressure variation and risk factor for hypertension. Because insulin resistance and blood pressure cosegregate in Mexican American families, we thus investigated the association between variations in 9 previously reported hypertension genes (ACE, AGT, AGTRI, ADDI, NPPA, ADDRB2, SCNN1A, GNB3, and NOS3) and insulin resistance. Families were ascertained via a coronary artery disease proband in the Mexican American Coronary Artery Disease Project. Individuals from 100 Mexican American families (nϭ656) were genotyped for 14 polymorphisms in the 9 genes and all adult offspring and offspring spouses were phenotyped for insulin sensitivity by hyperinsulinemic euglycemic clamp (nϭ449). AGT M235T and NOS3 A(Ϫ922)G and E298D polymorphisms were significantly associated with insulin sensitivity (Pϭ0.018, 0.036, 0.039) but were not significant after adjusting for body mass index. ADD1 G460W was associated with insulin sensitivity only after adjusting for body mass index. The NPPA T2238C and SCNN1A A663T were associated with decreased fasting insulin levels after adjusting for body mass index (Pϭ0.015 and 0.028). (HTN) is not benign; it is strongly associated with the development of atherosclerosis and left ventricular hypertrophy resulting in congestive heart failure, stroke, and age-related macular degeneration. 1-2 The risk of complications increases with increasing blood pressure (BP), particularly systolic blood pressure (SBP). 3,4 High BP is also a major antecedent for renal failure and, after diabetes, is the second most common cause of chronic renal failure in the adult population. 1,5 Insulin resistance (IR) is a potentially important intermediate phenotype for HTN in certain populations, particularly in Mexican Americans (MAs). Cross-sectional studies have revealed correlations between IR and BP in this and other ethnic groups. 6 -8 Hyperinsulinemia preceded and predicted the development of HTN in an 8-year prospective study of MAs in San Antonio, Texas 6 and has exhibited major gene effects in at least 3 ethnic groups. 9 -11 By path analysis, we have shown that BP and IR cosegregate and have a significant genetic component independent of any relationship to body mass index (BMI). 12 This cosegregation was further confirmed in our genome scan linkage analysis, wherein we identified several regions of coincident linkage of insulin sensitivity and BP. 13 For example, fasting insulin, SBP, and mean arterial blood pressure were all mapped to the same region on chromosome 7 (112 to 128 cM). Considered together, these findings provide strong support for the concept that IR is an intermediate and genetically regulated phenotype for HTN.Although the aforementioned data may suggest that IR is a proximate cause of HTN, an alternative possibility is that both are pleiotropic manifestations of the same underlying susceptibility. In support of this latter hypothesis has been the observation that several large scale clinical trials of pharmacological agents whose targets are t...

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Atrial natriuretic peptide contributes to the physiological control of lipid mobilization in humans

Cited by 157 publications

References 32 publications

Genome-Wide Scan for Linkage to Obesity-Associated Hypertension in French Canadians

Genome-Wide Scan for Linkage to Obesity-Associated Hypertension in French Canadians

Obesity and polymorphisms in genes regulating human adipose tissue

Hypertension Genes Are Genetic Markers for Insulin Sensitivity and Resistance

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