Influence of peptides associated with the gastrointestinal tract on ovine perirenal fat lipogenesis.

Several peptides associated with the gastrointestinal tract have hccn shown to affect the metabolism of adipose tissues for example gastric inhibitory polypeptide (GIP) and somatostatin (SS) respectively stimulate and inhibit insulin enhanced glucose uptake in isolatcd rat adipocytes [1,2]. GIP has also been reported t o enhance insulin stimulated fatty acid incorporation into rat adipose tissue cxplanta 1.31. In the same species, epidermal growth factor (EGF) was shown to stimulate fatty acid synthesis in isolated hepatocytes [4]. Apparently little is known about the role o f peptides associated with the gut o n ruminant fat metabolism IS], The effects of three peptides (porcine GIP. S S and mouse EGF) on lipogenesis in ovine adipose tissue was therefore investigated. Samples o f pcrirenal fat (5-log) were removed aseptically aftcr slaughter from female or male castrated Dorset or Suffolk-cross shccp aged between 5-9 months. In the subsequent experiments no differcnccs between the responses shown by the two sexes were noted. Fat explants (20-30 mg) were then maintained for 24h in Medium IYY with Earlc's salts ( M I S ) as described by Robertson et al 151. The peptides under test were added at the start of the incubation. In additional incuhafions the influence of these peptides on bovine insulin's (1O'"M) ahility to stimulate lipogencsis was also investigated. After the 24h incuhafions the explants were placed in 25 mM-Hepcs buffered MlYY, pH 7.4 containing [I-"C] acetate and the peptides under test at the same concentration as used for the 24h incubations. Incorporation of ["C] acetate into total lipid (extracted by Dole's extraction method) was used to determine the rate of lipogcnesis. SS was obtained from Bachcm, UK, porcine GIP from Sigma, Dorsct. UK or Peninsula Laboratories, Mcrseyside. UK, bovine insulin from Sigma, Dorset. UK and recombinant mouse EGF was a gift from Coopers Animal Health (Australia) Ltd. The effects of the gut hormones in the presence and absence of added insulin on lipogenesis are presented in the figure. GIP alone significantly (P<0.01) stimulated lipogenesis. Maximal effect was achieved at 10-" to lo-% GIP. The extent of the stimulation was routinely reduced when the GIP concentration was increased to IO'M. The source of GIP did not influence the trend of the results. As was t o be expected insulin stimulated lipogenesis. GIP reduced the magnitude of this stimulation. E G F reduced the basal rate of lipogenesis at all concentrations tested. EGF also reduced the extent of the insulin stimulation of lipogenesis. S S had a smaller effect on basal lipogencsis than that seen with EGF, at lo-% S S reduced i t by 29.9 26.7 and EGF by 66.4 2 7.5% (mean 2 SEM of 3 experiments). S S also reduced the extent of lipogenesis in the presence of lo-'% insulin. These studies suggest that these peptides associated with the digestive tract may have important roles in the regulation of ovinc fat metaholism in.