Regulation of Lipid Desaturation and Turnover in Adipose
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Date
2018-10-26
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Abstract
Mechanisms in the regulation of lipogenesis or lipolysis in adipose tissue significantly contribute to not only uncovering novel treatments for metabolic diseases in human health, but also creating economic profits to markets by improving livestock meat quality. This dissertation describes the investigation of lipid desaturation by ectopically expressed porcine stearoyl-desaturase 1 (SCD1) in non-adipocytes and the extent of lipolysis mediated by various kinds of selective ß-adrenergic receptor (ß-AR) agonists ex vivo and in vitro.
Inducible lentiviral expression vectors were generated for over-expression or knock-down of porcine SCD1 in the swine kidney 6 (SK6) cells. pSCD1-transduced SK6 cells successfully overexpressed pSCD1 expression as compared to uninduced SK6 (P < 0.05). pSCD1-transduced SK6 cells transfected with pSCD1shRNA significantly suppressed pSCD1 expression. Furthermore, the pSCD1-transduced cells incubated with 50 µM palmitic acid increased the synthesis of palmitoleic acid nearly 4-fold, indicating that the pSCD1-transduced cells successfully can induce the ∆9 desaturation of palmitic acid to palmitoleic acid.
ß-AR subtypes were characterized in bovine subcutaneous (s.c.) and intramuscular (i.m.) adipose tissues with the use of selective ß1-, ß2- and ß3-AR agonists. The most abundant ß-AR mRNA in both adipose tissues was the ß2-AR (P < 0.05). Isoproterenol, ractopamine, and zilpaterol stimulated the release of glycerol and nonesterified fatty acid (NEFA) from s.c. adipose tissue, but BRL-37344 did not affect lipolysis in s.c. adipose tissue in ex vivo cultures. A novel ß-agonist suppressed the stimulation of cAMP production mediated by ß1- and ß2-AR agonists in s.c. adipose tissue (P <0.05). In contrast, these ß-AR agonists were not effective in i.m. adipose tissue. Finally, we investigated mechanisms regulating ß-AR stimulation mediated by dobutamine, salbutamol, and a novel ß-agonist in primary bovine s.c. and i.m. adipocytes. The stimulation of ß1-AR through dobutamine significantly activated adenylyl cyclase and protein kinas A, and concurrently increased glycerol release in s.c. adipocytes, more than salbutamol did (P < 0.05). The effects by ß-AR agonists were blocked by propranolol. A novel ß-agonist inhibited adenylyl cyclase and protein kinase A activation in s.c adipocytes (P < 0.05). In contrast, these ß-AR agonists were not effective in i.m. adipocytes. In conclusion, this research has suggested the opportunity not only to develop a non-rodent biomedical model of obesity and metabolic disease but also to contribute to the understanding of functionality of ß-AR subtypes in adipose tissue during cattle growth and maturity.
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Porcine SCD1, ß-Adrenergic receptors, ß-Adrenergic agonists