Regulation of the expression of angiotensin-converting enzyme 2 by polyunsaturated fatty acids in porcine adipocytes1

Abstract

Using suppression subtractive hybridization technique, we found that 2 novel genes (AEUG1 and AEUG3) were highly expressed in the adipocytes compared with preadipocytes. We then identified that these 2 genes were both angiotensin-converting enzyme 2 (ACE2). We applied 3'RACE (rapid amplification of cDNA end), 5'RACE, and PCR to obtain the full-length porcine ACE2 cDNA sequence. Because eicosanoids derived from PUFA are involved in regulating blood pressure, we hypothesized that PUFA can regulate the expression of the vasodilator ACE2. Preadipocytes from Landrace pigs were induced to differentiate for 4 d, then treated with 50 μM of different PUFA, CLA, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or stearic acid (18:0). Addition of EPA or 18:0 for 48 h did not change the ACE2 mRNA abundance, whereas the treatments of arachidonic acid, CLA, and DHA significantly decreased ACE2 mRNA abundance after 48 h (P ≤ 0.05). Treatment with PUFA did not change (P > 0.05) type I and type II angiotensin receptor mRNA abundance. To further understand how PUFA metabolites affect ACE2 mRNA expression, we inhibited individual enzymes that are involved in eicosanoid production. We found that 3 individual eicosanoid pathway enzyme inhibitors recovered the PUFA effect on the expression of ACE2, indicating these pathways are involved in mediating the PUFA function. In conclusion, we obtained the full-length porcine ACE2 cDNA sequence and found PUFA could downregulate the expression of ACE2 through its metabolites without changing the expression of their receptor in porcine adipocytes.

Identification of Selection Footprints on the X Chromosome in Pig

“…These genes are relevant with reproduction, immune and meat quality based on the gene database in NCBI (http://www.ncbi.nlm.nih.gov/gene/). Among of them, ACE2 with the function of inhibiting the differentiation of adipocytes [26] is overlapped with the potential selection region of 13.06∼13.09 Mb which was identified by XPEHH and iHS, and gene ACSL4 related with meat quality is overlapped with the region of 105.37∼105.45 Mb detected by XPEHH [27]. 2 genes (ATP1B4 and HTR2C), which are overlapped with the potential selection regions in Yorkshire, are relevant with sow reproduction traits, such as infanticide phenomenon and perinatal development of embryo [28], [29].…”

Docosahexaenoic acid suppresses the expression of FoxO and its target genes

“…All participants gave written permission, and the experiment was approved by the ethics committee of National Taiwan University Hospital. Procedures for human and porcine preadipocyte isolation, cell culture and differentiation were described previously [16,17].The SK-HEP-1 cells and differentiated adipocytes were cultured in DMEM and DMEM/F12, respectively, overnight and then treated with or without a fatty acid, palmitic acid (PA), oleic acid (OA) or DHA, bound to 1% fatty acid-free bovine serum albumin (BSA) for 24 h. Total RNA was extracted from tissues and cells by the guanidinium thiocyanatephenol-chloroform extraction method [18]. Genomic DNA was then removed from the RNA samples by the TURBO-DNase free kit (Applied Biosystems, Foster City, CA, USA) followed by reverse transcription into cDNA using the High Capacity cDNA Reverse Transcription kit (Applied Biosystems, Foster City, CA, USA).…”

Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress

“…Its retention on the cell surface is regulated by cleavage (shedding) of the ectodomain by ADAM17 (a disintegrin and metalloproteinase 17) [15]. In adipocytes, polyunsaturated fatty acids increase the expression of ACE2 and ADAM17 concurrently, leading to a decrease in the expression of ACE2 at the cell surface [16]. Not only do dietary fats regulate ACE2 expression, but also metabolic diseases, such as T2DM (Type 2 diabetes mellitus), disrupt its expression [17].…”