Expression and Secretion of an Atrial Natriuretic Peptide in Beige-Like 3T3-L1 Adipocytes

Abstract

The browning of white adipose tissue (beige adipocytes) stimulates energy expenditure. Omega-3 fatty acids have been shown to induce thermogenic action in adipocytes via G-protein coupled receptor 120 (GPR120). Atrial natriuretic peptide (ANP) is a peptide hormone that plays the role of maintaining normal blood pressure in kidneys to inhibit Na+ reuptake. Recently, ANP was found to induce adipocyte browning by binding to NPR1, an ANP receptor. However, the expression of ANP in adipocytes has not yet been studied. Therefore, in this study, we investigate the expression of ANP in beige-like adipocytes induced by docosahexaenoic acids (DHA), T3, or a PPAR agonist, rosiglitazone. First, we found that brown adipocyte-specific genes were upregulated in beige-like adipocytes. DHA promoted ANP expression in beige-like cells, whereas DHA-induced ANP expression was abolished by GPR120 knockout. ANP secretion of beige-like adipocytes was increased via PKC/ERK1/2 signaling in the GPR120 pathway. Furthermore, ANP secreted from beige-like adipocytes acted on HEK-293 cells, the recipient cells, leading to increased cGMP activity. After the NPR1 knockdown of HEK-293 cells, cGMP activity was not changed. Taken together, our findings indicate that beige-like adipocytes induce ANP secretion, which may contribute to improving obesity-associated metabolic disease.

The WNT/Ca2+ pathway promotes atrial natriuretic peptide secretion by activating protein kinase C/transforming growth factor-β activated kinase 1/activating transcription factor 2 signaling in isolated beating rat atria

“…These results indicate that Wnta1 promoted ANP secretion and a positive inotropic effect in atrial mechanical dynamics mainly via the WNT/Ca 2+ pathway. The mechanism involved in Wnta1 activation of PKC in the present study is in line with previous studies A C B [9,13] and consistent with investigations showing that activated PKC was effective in promoting the secretion of ANP [21,22]. Our data also support studies reported upregulation of ANP expression after activation of WNT in myocardial hypertrophic animal models [13,20].…”

Regulatory role of atrial natriuretic peptide in brown adipose tissue: A narrative review

“…Expression and secretion of ANP are primarily accomplished in the heart, but ANP expression has been reported to occur in adipocytes as well 31 . Bae et al 32 investigated the expression of ANP in brown/beige adipocytes induced by docosahexaenoic acid, triiodothyronine, or the peroxisome proliferator‐activated receptors (PPARs) agonist rosiglitazone. Brown adipocyte‐specific genes were found to be upregulated in 3T3‐L1 cells with the increased secretion of ANP, suggesting that 3T3‐L1 cells had undergone browning and differentiated into beige‐like adipocytes.…”

“…Expression and secretion of ANP are primarily accomplished in the heart, but ANP expression has been reported to occur in adipocytes as well. 31 Bae et al 32 between cGMP and mTORC1 activation and that mTORC1 activation was necessary for NP-induced browning of adipocytes. They also confirmed that mTORC1 was involved in both PKA and PKG-mediated pathways, which demonstrated its importance in the adipose browning process.…”

<p>Reduced Beige Adipogenic Potential in Subcutaneous Adipocytes Derived from Obese Chinese Individuals</p>

“…23 T3 promotes the expression of PGC-1α, the master transcriptional coactivator of mitochondrial biogenesis in fat depots to enhance BAT thermogenesis. 24 The results of an animal study suggested that thyroid hormone also additionally mediates UCP-1-independent thermogenesis. 25 BAinduction treatment did not increase the expression of UCP-1 in adipocytes derived from the obese group, but mitochondrial respiratory function, PGC-1α gene expression did increase significantly, which may due to the effect of T3, although the content of increasement was lower compared to normal-weight ones.…”