Abstract
Compared with the rodent, the domestic pig is a much better animal model for studying adipogenesis and obesity-related diseases. Currently, the role of Akt2 and Sirt1 in porcine adipogenesis remains elusive. In this study, we defined the effect of Akt2 and Sirt1 on porcine preadipocyte lipogenesis and the regulatory mechanism. First, we found that Akt2 was widely expressed in porcine various tissues and at high level in adipose tissue. Further analysis showed that the expression level of Akt2 was much higher in adipose tissue and adipocytes of the Bamei pig breed (a Chinese indigenous fatty pig) than in that of the Large White pig breed (a Lean type pig), whereas the level of Sirt1 expression was opposite. The expression levels of Sirt1 and Akt2 gradually increased during adipogenic differentiation. Adipogenesis was robustly inhibited in Akt2 deficient fat cells, whereas it was promoted in Sirt1 deficient cells using the lentiviral–mediated shRNA approach. Interestingly, adipogenesis returned to normal in Akt2 and Sirt1 dual–deficient cells, showing that the pro- and anti–adipogenic effects were balanced. Sirt1 inhibited transcriptional activity of Akt2 in a dose-dependent way. Interaction of endogenous Akt2 and Sirt1 was gradually enhanced before day 6 of differentiation, and then attenuated. Akt2 and Sirt1 also interacted with C/EBPα in adipocytes. Moreover, knockdown of Akt2 or/and Sirt1 affected pro–lipogenesis of insulin–stimulated by PI3K/Akt pathway. We further found that Sirt1 respectively interacted with PI3K and GSK3β which were key upstream and downstream components of PI3K/Akt pathway. Based on the above findings, we concluded that the crosstalk between C/EBPα and PI3K/Akt signaling pathways is implicated in Akt2 and Sirt1 regulation of adipogenesis.
Highlights
Animal models of human diseases have always played a central role in biomedical research for the exploration and development of new therapies
Akt2 expression was detected by real-time qPCR and Western blot
The results indicated that Akt2 mRNA and protein were widely expressed in various tissues of 3–day–old piglets (Fig. 1A, B) and 180–day–old adult pigs (Fig. 1C, D)
Summary
Animal models of human diseases have always played a central role in biomedical research for the exploration and development of new therapies. Compared to rodent animals including mice (Mus musculus) and rats (Rattus norvegicus), pigs (Sus scrofa) offer many advantages including close similarity to human physiological characteristic and genetic modulation of fat deposition [1,2,3]. The domestic pig is a much better animal model for studying adipogenesis and obese-related diseases. Excessive fat deposition would cause bad meat quality and severe damage to systemic metabolic health. Whether in adipose tissue or muscle, contributes importantly to various aspects of meat quality and is central to the nutritional value of meat. Understanding novel mechanism of genes regulating adipogenesis is helpful to develop strategies for controlling fat deposition of pigs and the treatment of lipid metabolic diseases
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