Angiotensin II Increases Lipogenesis in 3T3-L1 and Human Adipose Cells*

Abstract

Angiotensin II (Ang II) is one of numerous hormones recently shown to be synthesized and secreted by adipose cells. Although the function of Ang II in adipose tissue is unknown, several studies indirectly suggest that it may be involved in control of adiposity. Little is known, however, about direct actions of Ang II in adipose cells. To further investigate this issue, we first characterized the type of Ang II receptors in 3T3-L1 adipocytes. We then tested the hypothesis that Ang II exerted direct actions on adipocyte metabolism using both 3T3-L1 and human adipocyte models. We report here that Ang II significantly increased triglyceride content and the activities of two key lipogenic enzymes (fatty acid synthase, FAS and glycerol-3-phosphate dehydrogenase, GPDH) in 3T3-L1 adipocytes, and that these effects were mediated through the type-2 Ang II receptor. We also report that Ang II exerted similar effects in human adipose cells maintained in primary culture. Finally, we demonstrate that Ang II increased the transcription rate of the FAS and ob genes in 3T3-L1 and human adipose cells. These results indicate that Ang II may be involved in control of adiposity through regulation of lipid synthesis and storage in adipocytes.

Blockade of the Renin-Angiotensin System Ameliorates Apelin Production in 3T3-L1 Adipocytes

“…1d) during adipocyte differentiation. These findings were consistent with those of Jones et al [13] but not Mallow et al [25]. The apparent difference might be due to the length of experimental period.…”

“…Since that time, mRNA and proteins of the Ang II-forming enzymes in the RAS, including renin and ACE1, have been identified in various rodent or human adipocyte studies [22,23], while Ang II was shown to have effects on human adipose conversion and gene expression of RAS [24]. Jones et al showed that Ang II increased lipogenesis through AT2R in 3T3-L1 adipocytes [13], while another study by Mallow et al detected AT1 receptor proteins throughout the 12-day developmental period of 3T3-L1 cells [25]. Other in vivo studies in mice also reported that AT1R was the predominant Ang II receptor during adipogenesis [15,17], while others found AT2R to predominate [14,26].…”

“…While the relationship between the two receptors may be clear in the cardiovascular system, their functions are not clearly understood in adipose tissue [11]. Although one study of rat and human adipocytes showed that Ang II increased lipogenesis via AT1R [12], another study showed Ang II exerted this effect via AT2R in 3T3-L1 adipocytes [13]. More recently, one study found that by knocking out AT2R in mice, adipose cell size could be reduced and that this gene might be manipulated to reverse obesity caused by the overexpression of angiotensinogen in the adipose tissue of mice [14].…”

Determination of Body Fat Distribution by Dual-Energy X-ray Absorptiometry and Attenuation of Visceral Fat Vasoconstriction by Enalapril

“…Angiotensin II promoted lipid synthesis and storage in adipocytes [16], produced vasoconstriction and inhibited lipolysis in adipose tissue [17]. Stimulation of the mucosal afferent nerves in the gut produced peripheral vasoconstriction mediated by activation of the renin-angiotensin system [18].…”

Angiotensin-converting enzyme gene insertion/deletion polymorphism in nutritional disorders in children

“…The most-studied genes are those responsible for the control of adipose tissue metabolism and energy balance. For example, fat mass and obesity-associated (FTO) genes are related with weight gain and obesity during childhood [4,8,12,13].…”