Local Renin Angiotensin Expression Regulates Human Mesenchymal Stem Cell Differentiation to Adipocytes

Matsushita, Kenichi; Wu, Yaojiong; Okamoto, Yoshihisa; Pratt, Richard E.; Dzau, Victor J.

doi:10.1161/01.hyp.0000248211.82232.a7

Cited by 106 publications

(107 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Angiotensin II (Ang II), the major bioactive peptide of the RAS, signals the recruitment of new adipocytes from preadipocytes 4 in adipose tissue and mesenchymal stem cells. 12 Thus, Ang II from mature adipocytes may induce preadipocyte maturation in a paracrine manner. 13 Furthermore, Ang II plays an important role in enlarging mature human adipocytes by increasing triglyceride content.…”

Section: Introductionmentioning

confidence: 99%

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

et al. 2008

View full text Add to dashboard Cite

Objective: There is emerging evidence that angiotensin stimulates adipocyte differentiation and lipogenesis. This study tested the hypothesis that inhibition of angiotensin II by treatment with an angiotensin-converting enzyme inhibitor, perindopril, would reduce fat mass in rats. Design: After a 12-day baseline, rats were divided into two groups: one was untreated and the other received perindopril (1.2 mg kg À1 per day) in drinking water for 26 days. Subjects: In total, 16 male Sprague-Dawley rats aged 10 weeks at the start of the study. Measurements: Plasma leptin was measured in samples collected at baseline, half-way through and at the end of treatment. Body weight, food and water intake were measured daily throughout the experiment. Body fat mass, bone and lean mass were determined by dual energy X-ray absorptiometry (DEXA) at the end of the treatment period. Results: Daily food intake was the same in both groups throughout the study. By the end of treatment, animals receiving perindopril showed a modest reduction in weight gain relative to the untreated animals (62.4 ± 5.0 g vs 73.0 ± 4.0 g; Po0.05). DEXA analysis showed that body composition was greatly altered and the perindopril-treated group had 26% less body fat mass than the untreated group (61.0 ± 5.2 g vs 44.4 ± 4.2 g; Po0.01). The reduction in body fat mass was correlated with reductions in the weight of both the epididymal and retroperitoneal fat pads (Po0.001). Similarly, plasma leptin was reduced by perindopril treatment (4.64 ± 0.56 ng ml À1 ) compared to the untreated group (8.27 ± 1.03 ng ml À1 ; Po0.001). In contrast, there were no differences in lean or bone mass between the two groups. Conclusion: Oral treatment with perindopril selectively reduced body fat mass without influencing daily food intake. In contrast, there were no differences in lean or bone mass between the two groups.

show abstract

Section: Introductionmentioning

confidence: 99%

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Moreover, it has been suggested that AT 1 receptor blockade and AT 2 receptor stimulation increases differentiation from mesenchymal stem cell in vitro. 22 In our earllier report, we showed that the deficiency of AT 1 a receptor, a major subclass of AT 1 receptor, increased the adipocyte differentiation and the number of small-sized adipocytes in atherosclerotic model mice. 17 The role of another subtype of AT 1 receptor, AT 1 b receptor, is totally unknown.…”

Section: Angiotensin II and Adipocyte Differentiationmentioning

confidence: 89%

Role of renin–angiotensin system in adipose tissue dysfunction

Iwai

Horiuchi

2009

Hypertens Res

View full text Add to dashboard Cite

Blockade of angiotensin II type 1 (AT 1 ) receptor improves insulin sensitivity and diabetic condition. In short-term regulation, angiotensin II changes lipid metabolism and in long-term regulation, it affects insulin sensitivity and adipocyte differentiation in adipose tissue. These effects are mainly mediated by AT 1 receptor. AT 1 receptor blocker improves insulin sensitivity and induces adipocyte differentiation by increasing peroxisome proliferator-activated receptor-c (PPARc) and transcription factors in adipose tissue in diabetic and atherosclerotic models. Clinical studies indicate that AT 1 receptor blockers prevent the new onset of diabetes and improve insulin sensitivity. On the other hand, AT 2 receptor stimulation appears to cause antagonistic actions against AT 1 receptor signaling. Although further investigations are necessary on the AT 2 receptor function in adipose tissue, studies using AT 2 receptor agonists, in addition to those using AT 1 receptor blockers, would contribute to the treatment of metabolic syndrome and associated pathological disorders.

show abstract

“…Matsushita et al 5 indicate an enhancing effect of AT 1 receptor activation on adipogenesis; however, such an effect through endogenous Ang II is weaker than that of AT 2 receptor signal blockade. The detailed downstream targets in MSC differentiation through the AT 1 and AT 2 receptor have not been revealed, and this should be addressed to elucidate the role of RAS in the metabolic syndrome.…”

mentioning

confidence: 99%

“…ARB has 2 different effects: blockade of AT 1 receptors and increased stimulation of AT 2 receptors. Matsushita et al 5 showed that AT 2 receptor activation inhibits stem cell differentiation and prevents them from achieving their cell fate. The effects of an ARB on this differentiation are mediated by AT 2 receptor stimulation rather than by AT 1 receptor blockade.…”

mentioning

confidence: 99%

Emerging Concept of Adipogenesis Regulation by the Renin–Angiotensin System

2006

View full text Add to dashboard Cite

T he renin-angiotensin system (RAS) has been the focus of attention not only for its classical action through circulating RAS but also its local actions in tissues such as the brain, 1 liver, 2 lung, 3 and adipose tissue. 4 The roles of the local RAS in adipose tissue have recently been highlighted, because obesity is one of the major risks for the metabolic syndrome with hypertension and glucose intolerance. However, there have been inconsistent reports on the role of the adipose tissue RAS. The role of local RAS in adipogenesis has been discussed but is not well elucidated.In this issue of Hypertension, Matsushita et al 5 examined the role of local RAS during adipocyte differentiation using human mesenchymal stem cells (MSCs) instead of preadipocytes in an elegant fashion. They reported the influence of RAS on MSCs as follows (Figure 1): (1) Comparison of the expression of RAS components between MSCs and differentiated adipocytes revealed that mRNA of renin and the angiotensin II (Ang II) type-2 (AT 2 ) receptor were highly expressed, and Ang II concentration was significantly increased in differentiated adipocytes; (2) administration of Ang II with or without an Ang II type-1 (AT 1 ) receptor blocker (ARB), valsartan, in MSC during adipogenesis showed that Ang II inhibited adipogenesis, and AT 2 receptor activation by valsartan further inhibited it; and (3) moreover, treatment with valsartan alone also inhibited adipocyte differentiation. These results suggest that the local RAS, especially AT 2 receptor signaling, has a crucial role in adipogenesis.Evidence has accumulated that AT 2 receptor stimulation not only opposes the AT 1 receptor but also has unique effects independent of an interaction with AT 1 receptor signaling.

show abstract

Local Renin Angiotensin Expression Regulates Human Mesenchymal Stem Cell Differentiation to Adipocytes

Cited by 106 publications

References 44 publications

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

Role of renin–angiotensin system in adipose tissue dysfunction

Emerging Concept of Adipogenesis Regulation by the Renin–Angiotensin System

Contact Info

Product

Resources

About