Roles of α-linolenic acid on IGF-I and GH/IGF system gene expression in porcine primary hepatocytes.

The main purposes of this study were to investigate the effects of alpha linolenic acid (ALA) on the insulin like growth factor (IGF) system of porcine primary hepatocytes with or without growth hormone (GH) or insulin and the potential role of peroxisome proliferator activated receptor a and c (PPARa/c) pathway. We found that 1 lM ALA increased IGFI secretion from hepatocytes at 48 and 72 h. Expression of hepatocytes IGFI, IGFII, GH receptor (GHR), insulin receptor (IR), IGF binding protein 3 (IGFBP3), and IGFBP4 mRNAs was up regulated by ALA treatment. GH (15 nM) alone or cotreated with ALA increased hepatocytes IGFI secretion and the expression of GHR and IGFBP1 mRNAs, but down-regulated IGFBP5 mRNA compared with appropriate control across ALA. GH also enhanced the ALA induced increase in the transcript levels of IGF-II and GHR, but tended to attenuate that of IGFBP4. Insulin (1 lM) alone or co treated with ALA improved IGF-I secretion and the expression of IGFBP3 mRNA, but decreased IGFBP1 mRNA versus appropriate control across ALA. Insulin also up regulated the expression of GHR, IR, IGFBP3, and IGFBP4 mRNAs, and tended to prevent the transcript levels of IGFI and IGFBP4 improved by ALA. Both PPARc agonist rosiglitazone and its antagonist GW9662 could elevated the IGFI secretion in dose-dependent manner but they had no interaction with ALA. However, GW7647, a PPARa agonist, increased IGFI secretion dose dependently, but the antagonist GW6471 was without effect. Moreover, GW6471 prevented the IGF I promoting effect of ALA. This suggests that the IGF-I promoting effect of ALA may be mediated by the PPARa pathway. (Authors abstract)
Animal growth is a complex process, important regulators of which are members of the growth hormone/insulin-like growth factor (GH/IGF) system, which includes the three peptides GH, IGFI and IGFII and their receptors and binding proteins. Previous studies have confirmed a crucial role for alpha linolenic acid (ALA) in modulating human health and disease. There is some evidence that ALA may also play a role in regulating growth and development. ALA (0.01 to1 lM for 72 h treatment) was reported to up regulate IGFI mRNA in bovine satellite cells obtained from steers implanted a trenbolone acetate and estradiol-17b in their right ear. The intent of this study was to investigate the effect of ALA on IGF-I secretion and GH/IGF system gene expression in hepatocytes and to determine whether it interacts with GH and insulin. In addition, PPARa and c synthetic ligands were used to elucidate the mechanism of ALA in regulating IGFI secretion. ALA increased IGFI secretion from porcine hepatocytes in a dose dependent manner in 72 h. The data demonstrate that ALA (1 lM) enhances the expression of mRNA within the GH/IGF system (i.e. IGFI, IGFII, GHR, IR, IGFBP2, IGFBP3, IGFBP4, and IGFBP6). It was demonstrated that hepatocyte IGFI secretion was increased by GH or insulin treatment alone. IGFI promoting effect was enhanced by ALA co treatment. IGFI production mediates the action of GH on somatic growth and tissue maintenance by an established mechanism. The results from the present study suggest that ALA increases IGFI secretion from porcine hepatocytes by activating PPAR a in a time and dose dependent manner. There was a synergistic effect between GH or insulin and ALA on IGFI secretion. The expression of mRNA within the GH/IGF system was also regulated by ALA, GH and insulin when administered separately or in tandem. (Editors comments)