The effect of ractopamine hydrochloride on gene expression in adipose tissues of finishing pigs1

Abstract

The long-term effect of feeding the catecholamine analog ractopamine (RAC; ractopamine hydrochloride, Elanco Animal Health, Indianapolis, IN) on the expression of genes involved in energy and lipid metabolism in subcutaneous adipose tissue was studied. Large White pigs (84 kg) were fed corn- and soybean meal-based diets supplemented with 0, 20, or 60 mg/kg of RAC for 14, 28, or 42 d. Expression (mRNA abundance) in adipose tissue of sterol regulatory binding protein-1 (SREBP-1), PPARα, PPARγ2, fatty acid synthase (FAS), glucose transporter 4 (GLUT4), and stearoyl-CoA desaturase was determined by Northern blotting. Feed intakes did not differ, and RAC (20 and 60 mg/kg) improved BW gain at d 14, 28, and 42 (P < 0.05) and increased loin eye area (measured on d 42 only; P < 0.05). Expression of SREBP-1 and PPARγ2 declined (P < 0.05) with RAC by d 28 and 42, whereas expression of PPARα was increased (P < 0.05) on d 14, 28, and 42. After 14 d, expression of FAS and GLUT4 was decreased (P < 0.05) with 60 mg/kg of RAC, whereas both RAC concentrations attenuated FAS expression on d 28 and 42. Overall, adipose tissue stearoyl-CoA desaturase expression was not affected by RAC but showed somewhat less expression (P < 0.15) on d 28 at 60 mg/kg of RAC. Although prolonged, chronic RAC feeding most likely downregulates adipose tissue membrane β-adrenergic receptors, mRNA abundances of anabolic lipid metabolism transcription factors, glucose transporters, and enzymes (SREBP-1, PPARγ2, FAS, GLUT4) were still attenuated up to d 42. Conversely, a transcription factor related to oxidative metabolism expression (PPARα) was enhanced. We conclude that even after 42 d, RAC still decreased expression of lipogenic genes in adipose tissue by yet undefined cyclic adenosine monophosphate-directed mechanisms, but in contemporary lean pigs, this effect is likely of limited practical significance.

Metabolic and behavioral effects of ractopamine at continuous low levels in rats under stress

“…Other studies have shown that BAA use could reduce adipose tissue and increase fat cell apoptosis (Eadara et al 1989). Further, in pigs, RAC effects were observed in the AMPc pathway genes, such as reduction of FAS and GLUT-4 in adipose tissue (Halsey et al 2011). However, in this study, probably due to the stress, an opposite effect was observed related to that expected from the RAC, suggesting increased lipogenesis.…”

Ractopamine effect on lipid metabolism and GLUT4 amount of finishing pigs

“…Before slaughter in this experiment, the animals were fasted for 12 h. Thus, SAT, RPAT, and MT were obtained after slaughter and may not reflect the actual scenario of the amount of active enzymes in the adipose tissue of living animals. In the works of Halsey et al (4) and Reiter et al (3), pigs were slaughtered without any period of food deprivation, which may be reflected in the results obtained by these authors. Liu et al (25), however, did not explain whether the animals in their experiment were fasted or not, but their results showed that RAC did not affect the amount of GLUT4 mRNA present in the adipose tissue of the animals.…”

“…However, in contrast to the results of Halsey et al (4) and Reiter et al (3), this result was obtained only with the amount of GLUT4 present in the skeletal muscle tissue of animals ( Figure 4). Halsey et al (4) found that 28 days of supplementation with RAC was able to decrease the amount of GLUT4 mRNA present in the adipose tissue of the animals. Reiter et al (3), while increasing the time of exposure to the agonist (52 days), were able to obtain similar results for GLUT4 mRNA present in the adipose tissue and further proved that the same effect (decrease) was also found in skeletal muscle tissue.…”

“…Some of the effects of RAC supplementation on lipid metabolism in pigs include the regulation of gene expression related to the breakdown of body fat and the genes that regulate enzymes involved in lipogenesis (3,4). As other studies are still necessary to help to understand the possible pathways of this drug in pigs, metabolically important enzymes, such as lipoprotein lipase, also require further investigations in this animal model.…”

Effect of ractopamine on Nile tilapia in the end of grow-out period

“…In pigs, another action of ractopamine on fat metabolism is the promotion of lower fat accretion by reducing lipogenesis (Bergen, 2001), which could be explained by the reduction of the sensitivity on adipose tissue to insulin, as it happens in pigs under βAA stimulation, and an evidence of lipogenesis inhibition (Mills et al, 2002). Furthermore, according to recent works focusing on lipogenic gene expression in the adipose tissue of finishing pigs, ractopamine can reduce the RNA transcription of genes related to lipid synthesis, such as sterol regulatory binding protein-1 (SREBP-1), which is a transcriptional factor that drive genes involved in the synthesis of fatty acids (Horton et al, 2003) and fatty acid synthase (Reiter et al, 2007;Halsey et al, 2011), a key enzyme involved in the synthesis of fatty acids (Ferreira et al, 2013). Although no difference was found in the weight gain between control and treatment groups during the experimental period (average of 170 g) ( Table 3), considering that ractopamine may have more efficacy on blocking lipogenesis instead of stimulating lipolysis (Mills et al, 2003), the animals that received ractopamine may have had a decrease of lipogenesis rate, especially at 8 mg kg −1 of ractopamine.…”