Adipose Tissue–Specific Regulation of Angiotensinogen in Obese Humans and Mice: Impact of Nutritional Status and Adipocyte Hypertrophy

Yasue, Shintaro; Masuzaki, Hiroaki; Okada, Sadanori; Ishii, Takako; Kozuka, Chisayo; Tanaka, Tomohiro; Fujikura, Junji; Ebihara, Ken; Hosoda, Kiminori; Katsurada, Akemi; Ohashi, Naro; Urushihara, Maki; Kobori, Hiroyuki; Morimoto, Naoki; Kawazoe, Takeshi; Naitoh, Motoko; Okada, Mitsuru; Sakaue, Hiroshi; Suzuki, Shigehiko; Nakao, Kazuwa

doi:10.1038/ajh.2009.263

Cited by 100 publications

(93 citation statements)

References 18 publications

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“…In rodent models, angiotensin II contributes to adipose tissue proliferation by binding on both AT1 and AT2 receptors (Kouyama et al 2005;Yvan-Charvet et al 2009), which is opposed by angiotensin 1-7 acting on Mas receptors (Santos et al 2008). Although data about AGT expression in subcutaneous adipocytes of obese and non-obese human patients remain controversial (Dusserre et al 2000;Yasue et al 2010;Okada et al 2010;Oberbach et al 2014;Van Harmelen et al 2000a, b), the plasma levels of circulating angiotensinogen have been found increased in obese patients ) and they were shown to decrease with the weight loss (Engeli et al 2005;Oberbach et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in miR-31 and miR-584 binding site in the angiotensinogen gene differentially influences body fat distribution in both sexes

et al. 2015

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Angiotensinogen (AGT), its active fragments and microRNA-31 (miR-31) play an important role in adipocyte differentiation. AGT contains a miR-31 polymorphic binding site. We hypothesize that the rs7079 polymorphism in the miR-31/584 binding site of the AGT gene could influence body fat distribution. A total of 751 subjects (195 men, 556 women) were enrolled in the study. The rs7079 genotypes were determined by qRT-PCR. Anthropometric measurements were taken on all subjects, who were subsequently divided into two groups: obese ([30 kg m -2 ) and non-obese (\30 kg m -2 ). Linear regression models were created to determine the contributions of sex, obesity status and rs7079 to all measured parameters. Adding the rs7079 genotype significantly contributed to the linear regression model for waist circumference (p = 0.013), hip circumference (p = 0.018) and supraspinal skin-fold thickness (p = 1 9 10 -3 ). Differences between sexes and between the obese and nonobese groups were observed. Waist circumference was lower in men carrying the A allele (p = 0.022); hip circumference was higher only in obese women carrying the A allele (p = 0.015). While men carrying the A allele had lower supraspinal skin-fold thickness (p = 0.022), this parameter was found to be higher in A allele carrying women (p = 3 9 10 -3 ). The higher total sum of skin-fold thickness in A allele carrying women was restricted to obese individuals (p = 0.028). The presence of the A allele was associated with both lower tricipital skin-fold thickness in non-obese women (p = 0.023) and a trend of higher thickness in non-obese men (p = 0.065). Significant associations of rs7079 in the AGT gene and body fat distribution were observed. The distribution followed opposing patterns in both sexes.

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Section: Introductionmentioning

confidence: 99%

Polymorphism in miR-31 and miR-584 binding site in the angiotensinogen gene differentially influences body fat distribution in both sexes

et al. 2015

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“…Locally acting RAS contains all components of RAS, including angiotensinogen (Agt), renin, and angiotensin-converting enzyme (ACE) together with AT 1 and AT 2 receptors (Cassis et al 2008) to produce the main effector of the system, angiotensin II (Ang II). While Agt is produced mainly in the liver of lean individuals, adipose tissue is another important source of Agt in obese individuals (Yasue et al 2010). The specific feature of adipose tissue RAS is its ability to produce Ang II not only via the renin and ACE pathway but also through cathepsins and chymase (Karlsson et al 1998).…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

Obesity-related hypertension: possible pathophysiological mechanisms

Vaněčková¹,

Maletı́nská²,

Behuliak³

et al. 2014

Journal of Endocrinology

129

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Hypertension is one of the major risk factors of cardiovascular diseases, but despite a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. The same is true for obesity, which is recognized as a major global epidemic health problem nowadays. Obesity is associated with an increasing prevalence of the metabolic syndrome, a cluster of risk factors including hypertension, abdominal obesity, dyslipidemia, and hyperglycemia. Epidemiological studies have shown that excess weight gain predicts future development of hypertension, and the relationship between BMI and blood pressure (BP) appears to be almost linear in different populations. There is no doubt that obesity-related hypertension is a multifactorial and polygenic trait, and multiple potential pathogenetic mechanisms probably contribute to the development of higher BP in obese humans. These include hyperinsulinemia, activation of the renin-angiotensin-aldosterone system, sympathetic nervous system stimulation, abnormal levels of certain adipokines such as leptin, or cytokines acting at the vascular endothelial level. Moreover, some genetic and epigenetic mechanisms are also in play. Although the full manifestation of both hypertension and obesity occurs predominantly in adulthood, their roots can be traced back to early ontogeny. The detailed knowledge of alterations occurring in the organism of experimental animals during particular critical periods (developmental windows) could help to solve this phenomenon in humans and might facilitate the age-specific prevention of human obesity-related hypertension. In addition, better understanding of particular pathophysiological mechanisms might be useful in so-called personalized medicine. Key Words" obesity " hypertension " sympathetic nervous system " renin-angiotensin system " critical developmental periods " epigenetics " rat

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“…The over-production of ROS and upregulation of TNF-α are implicated in the impairment of glucose uptake (Shiuchi et al, 2004;Wei et al, 2008a). The RAS components, angiotensinogen (AGT), angiotensinogen converting enzyme (ACE) and angiotensin II type 1 receptor (AT1), are expressed in adipose tissue (Cassis et al, 2008;Engeli et al, 2000;Kalupahana and Moustaid-Moussa, 2012;Yasue et al, 2010) and skeletal muscle (Johnston et al, 2011;Jones and Woods, 2003;Kadowaki et al, 2006;Vermes et al, 2003) suggesting that an imbalance between systemic and local RAS has the potential to exacerbate metabolic disorders.…”

Section: Introductionmentioning

confidence: 99%

Activation of systemic, but not local, renin-angiotensin system is associated with up-regulation of TNF-α during prolonged fasting in northern elephant seal pups

Suzuki

Vázquez‐Medina

Viscarra

et al. 2013

Journal of Experimental Biology

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SUMMARYNorthern elephant seal pups naturally endure a 2-3month post-weaning fast that is associated with activation of systemic renin-angiotensin system (RAS), a decrease in plasma adiponectin (Acrp30), and insulin resistance (IR)-like conditions. Angiotensin II (Ang II) and tumor necrosis factor-alpha (TNF-α) are potential causal factors of IR, while Acrp30 may improve insulin signaling. However, the effects of fasting-induced activation of RAS on IR-like conditions in seals are not well described. To assess the effects of prolonged food deprivation on systemic and local RAS, and their potential contribution to TNF-α as they relate to an IR condition, the mRNA expressions of adipose and muscle RAS components and immuno-relevant molecules were measured along with plasma RAS components. Mean plasma renin activity and Ang II concentrations increased by 89 and 1658%, respectively, while plasma angiotensinogen (AGT) decreased by 49% over the fast, indicative of systemic RAS activation. Prolonged fasting was associated with decreases in adipose and muscle AGT mRNA expressions of 69 and 68%, respectively, corresponding with decreases in tissue protein content, suggesting suppression of local AGT production. Muscle TNF-α mRNA and protein increased by 239 and 314%, whereas those of adipose Acrp30 decreased by 32 and 98%, respectively. Collectively, this study suggests that prolonged fasting activates a systemic RAS, which contributes to an increase in muscle TNF-α and suppression of adipose Acrp30. This targeted and tissue-specific regulation of TNF-α and Acrp30 is likely coordinated to synergistically contribute to the development of an IR-like condition, independent of local RAS activity. These data enhance our understanding of the adaptive mechanisms evolved by elephant seals to tolerate potentially detrimental conditions.

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Adipose Tissue–Specific Regulation of Angiotensinogen in Obese Humans and Mice: Impact of Nutritional Status and Adipocyte Hypertrophy

Cited by 100 publications

References 18 publications

Polymorphism in miR-31 and miR-584 binding site in the angiotensinogen gene differentially influences body fat distribution in both sexes

Polymorphism in miR-31 and miR-584 binding site in the angiotensinogen gene differentially influences body fat distribution in both sexes

Obesity-related hypertension: possible pathophysiological mechanisms

Activation of systemic, but not local, renin-angiotensin system is associated with up-regulation of TNF-α during prolonged fasting in northern elephant seal pups

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