GH and insulin affect fatty acid synthase activity in isolated porcine adipocytes in culture without any modifications of sterol regulatory element binding protein-1 expression

Abstract

The ability of GH to decrease fatness and insulin-regulated events such as lipogenic enzyme activities is well known in pigs. Nevertheless, the precise mechanism underlying these actions has not been elucidated yet. Expression of the transcription factor sterol regulatory element binding protein (SREBP)-1 has been reported as a key mediator of insulin action in rat hepatocytes and adipose cell lines. The present study aimed to determine whether the regulation of lipogenesis by GH and/or insulin in porcine adipocytes also involved SREBP-1. Isolated adipocytes, obtained from perirenal or s.c. adipose tissue samples of female pigs (51 0·4 kg; n=17), were cultured in serum-free medium in the absence or presence of these hormones for up to 4 days. Glucose incorporation and fatty acid synthase activity were increased by insulin in a dose-dependent manner in adipocytes of both sites. The increase was maximal at 1·7 and 17 nM in s.c. and perirenal adipocytes respectively, suggesting inter-depot differences in the regulation of lipogenesis by insulin. These insulinstimulated events were decreased by GH (1 nM). No change in SREBP-1 mRNA levels was observed in response to GH and/or insulin. Taken together, these data indicate that the regulation of lipogenesis by insulin and GH appears to not involve changes in SREBP-1 mRNA levels in porcine adipocytes.

Effect of growth hormone on fatty acid synthase gene expression in porcine adipose tissue cultures

“…A similar decrease in the enzymatic activity has been observed in cultures of adipose tissue explants (Lanna et al, 1994) and also in isolated adipocytes cultured for 48 h (Louveau and Gondret, 2004). However, the magnitude of the reduction in activity was smaller than that observed with swine adipose tissue explants biopsied after 1 to 4 weeks of in vivo treatment with pGH, which showed a 40 to 80% reduction in FAS activity (Harris et al, 1993;Donkin et al, 1996a;Lee et al, 2000).…”

“…It is indeed possible that the pGH might only act indirectly through modulation of the insulin-signaling cascade. The mechanism by which growth hormone interferes with the action of insulin on FAS gene transcription has not yet been totally elucidated (Louveau and Gondret, 2004). Magri et al (1990) observed that a decrease in insulin sensibility caused by growth hormone in swine adipose tissue was neither associated with changes in the number of insulin receptors nor in tyrosine kinases activity.…”

“…Therefore, the maximum capacity of adipose tissue to synthesize fatty acids de novo is related to the total amount and specific activity of lipogenic enzymes which in turn is dependent on the levels of mRNA that codify these enzymes (Clarke, 1993). Growth hormone attenuates the stimulatory effect of insulin on FAS gene transcription and mRNA concentration by increasing mRNA degradation in 3T3-F442A adipocytes (Yin et al, 1998;Yin et al 2001a) and is also known to decrease FAS activity and mRNA concentration in isolated porcine adipocytes (Louveau and Gondret, 2004). However the mechanism(s) by which growth hormone interferes with the action of insulin on FAS gene transcription has not yet been elucidated (Louveau and Gondret, 2004).…”

Insulin induced lipogenesis and enhanced mRNA level of sterol regulatory element binding protein-1c in primary porcine adipocyte

“…In the case of SREBP-1c, it was not clear whether the increase in FAS activity was the result of a direct effect of insulin on the adipocytes or the result of a transactivation of the FAS promoter, inducing a further increase in the FAS activity in these cells. However, a recent study showed that no change in SREBP-1 mRNA levels was observed in response to insulin in porcine adipocytes ( I Louveau et al 2004). The report differs from results of the present study.…”

The Single and Combined Effect of <i>MC4R</i> and <i>GH</i> Genes on Productive Traits of Pigs

“…However, its production was found not only in the hypothalamus, but also in other parts of the nervous system and organs in the digestive tract. The GH for a long time been investigated as an anabolic hormone that regulates the metabolism, stimulates growth and overall body weight, promotes tissue regeneration and cell survival (Louveau and Gondret, 2004). Synthesis and secretion of GH is controlled somatoliberin hypothalamic hormones and somatostatin.…”