Angiotensin II Increases Leptin Secretion by 3T3-L1 and Human Adipocytes via a Prostaglandin-Independent Mechanism

Abstract

We previously reported that angiotensin II (Ang II) increases adipocyte fatty acid synthesis and triglyceride content. Triglyceride stores or adiposity correlate positively with the amount of circulating leptin. Ang II was proposed to increase adipocyte differentiation and growth by promoting prostaglandin (PG) production. The purpose of this study was to determine whether Ang II increases leptin secretion via a PG-dependent mechanism. Physiologic doses of Ang II significantly increased leptin secretion by 3T3-L1 adipocytes and human adipocytes. Elevation of PG secretions was elicited at physiologic concentrations of Ang II (P < 0.05). Secretions of 6-keto PGF(1alpha), a stable derivative of PGI(2), and PGE(2) were induced by physiologic concentrations of Ang II in a time-responsive fashion (P < 0.05). Inhibition of PG synthesis by indomethacin and aspirin significantly suppressed basal as well as Ang II-induced PG levels, but did not significantly affect basal and Ang II-induced leptin secretion. In conclusion, although Ang II stimulates both leptin and PG secretion by adipocytes, regulation of leptin secretion by Ang II in adipocytes is not mediated by a PG-dependent mechanism.

Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue

“…A previous study demonstrated that Ang II can promote leptin release from human and mouse 3T3-L1 adipocytes by activating the AT1R-ERK1/2 pathway, illustrating a positive regulatory mechanism of leptin release that is consistent with our results. 10,26,27 However, no report to date has focused on the negative regulation of leptin release from mature VAs, and, to our knowledge, our work is the first to demonstrate a negative effect of Ang(1-7) on leptin release from mature VAs. On the contrary, in addition to AT1R, another Ang II receptor subtype (AT2R) expressed in adipocytes can mediate Ang II signaling to decrease insulin sensitivity, increase adipocyte mass, and mediate the deleterious effects of a HFD.…”

Enhanced leptin synthesis and secretion in vitro by human adipocytes from type 2 diabetic donors occurs only under hyperinsulinaemic conditions

“…Normal and type 2 diabetic human adipocytes were compared for glucose uptake and differentiation following passage to ensure the phenotype was retained. Murine 3T3-L1 cells cultured in medium supplemented with 10ng/ml insulin 16 were used as positive controls. For leptin secretion assays 5x10 3 normal or type 2 diabetic human preadipocytes were plated into the wells of triplicate 24 well plates in 300µl of medium.…”

“…We therefore examined the interaction that may exist between insulin and leptin at the level of the adipocyte by measuring the effects of insulin treatment on leptin secretion by adipocytes derived from normal and from diabetic donors which have been shown to exhibit insulin resistance in vitro. 15 A study in vitro was designed to avoid potential confounding influences from other factors that have been shown to enhance leptin secretion from adipocytes such as angiotensin II, 16 ghrelin, 17 oleic acid 18 and Wnt pathway activation. 19 …”

Exploration of the Relationship between Adipocytokines, Tradition Risk Markers, Nontraditional Risk Markers and Anthropometric Measurements in T2DM Patients

“…These include TNF-a and other pro-inflammatory cytokines, insulin, glucose, estrogens. Other vasoactive factors like angiotensin II or endothelin may also lead to leptin release [32], although this is still under 507 investigations as this phenomenon may occur locally and does not seem to affect plasma levels of leptin during angiotensin II infusion [33]. Leptin receptors (a family of splice variants OB-R, differing with the size of cytoplasmic C terminus) are expressed in number of different tissues, which brought the attention of researchers to the fact that leptin has a very widespread range of actions [23] [24] [34]- [36], particularly within the cardiovascular and immune system [37] [38].…”