Adenovirus-mediated interference of FABP4 regulates mRNA expression of ADIPOQ, LEP and LEPR in bovine adipocytes

Abstract

ABSTRACT. Fatty acid binding protein 4 (FABP4) is an important adipocyte gene, with roles in fatty acid transport and fat deposition in animals as well as human metabolic syndrome. However, little is known about the functional regulation of FABP4 at the cellular level in bovine. We designed and selected an effective shRNA (small hairpin RNA) against bovine FABP4, constructed a corresponding adenovirus (AD-FABP4), and then detected its influence on mRNA expression of four differentiation-related genes (PPARᵧ, CEBPA, CEBPB, and SREBF1) and three lipid metabolism-related genes (ADIPOQ, LEP and LEPR) of adipocytes. The FABP4 mRNA content, derived from bovine adipocytes, decreased by 41% (P < 0.01) after 24 h and 66% (P < 0.01) 495©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (1): 494-505 (2013) shRNA interference of FABP4 in bovine adipocytes after 72 h of AD-FABP4 infection. However, lower mRNA content of FABP4 did not significantly alter levels of differentiation-related gene expression at 24 h following AD-FABP4 treatment of bovinederived preadipocytes (P = 0.54, 0.78, 0.89, and 0.94, respectively). Meanwhile, knocking down (partially silencing) FABP4 significantly decreased ADIPOQ (P < 0.05) and LEP (P < 0.01) gene expression after 24 h of AD-FABP4 treatment, decreased ADIPOQ (P < 0.01) and LEP (P < 0.01) gene expression, but increased LEPR mRNA expression (P < 0.01) after a 72-h treatment of bovine preadipocytes. We conclude that FABP4 plays a role in fat deposition and metabolic syndrome by regulating lipid metabolism-related genes (such as ADIPOQ, LEP and LEPR), without affecting the ability of preadipocytes to differentiate into adipocytes.

Tissue alkaline phosphatase is involved in lipid metabolism and gene expression and secretion of adipokines in adipocytes

“…Knock-down of Fabp4 showed its importance in adipocyte metabolism, and it also showed that there was a significant decrease in the expression of Adipoq and Lep, but not in the expression of the adipogenic genes, Cebpb, Srebf1, Pparg and Cebpa [42]. These results are in agreement with gene expression kinetic data that revealed that the expression of Fabp4 occurs later than even Cebpa during adipogenesis [29] supporting the idea that FABP4 seems to be more related to adipose metabolism and less to preadipocyte differentiation.…”

Effects of genetic variants in the promoter region of the bovine adiponectin (ADIPOQ) gene on marbling of Hanwoo beef cattle

“…The full-length form tends to decrease glucose, whereas the globular form stimulates oxidation in muscle. Recent studies argued that ADIPOQ, which is also produced in brown adipose tissue (Kadowaki & Yamauchi, 2005;Morsci, Sellner, Schnabel, & Taylor, 2006), enhances fatty acid oxidation and associates with fatty acid binding proteins (Dall'Olio, Roberta, Buttazzoni, Zambonelli, & Vincenzo, 2009;Wei et al, 2013). The functional roles described above are related to fat mechanisms, and a human study suggests that ADIOPQ is associated with obesity and diabetes (Hsueh et al, 2003).…”

“…Polymorphisms in the ADIPOQ gene in pigs were also reported to be associated with fatty acid binding protein (FABP4), fat deposition, carcass traits (Dai et al, 2006;Dall'Olio et al, 2009;Wei et al, 2013), and reproductive traits (Houde, Murphy, Mathieu, Bordignon, & Palin, 2008).…”

The mitochondrial fatty acid synthesis (mtFASII) pathway is capable of mediating nuclear-mitochondrial cross talk through the PPAR system of transcriptional activation

“…Cells overexpressing MECR had significant increase of FABP4 expression (3.3 fold upregulation) and significant decrease of ELN expression (1.8 fold downregulation). Affected gene FABP4 encodes a fatty acid binding protein that has a role in transport of fats within the cell, fat deposition in animals, and metabolic syndrome [28]. FABP4 has been reported to carry long chain fatty acids and retinoic acid to nuclear hormone receptors such as the PPARs and RXRs [29].…”