Growth Hormone Enhances Arachidonic Acid Metabolites in a Growth Hormone Transgenic Mouse

Abstract

In a transgenic growth hormone (GH) mouse model, highly elevated GH increases overall growth and decreases adipose depots while low or moderate circulating GH enhances adipose deposition with differential effects on body growth. Using this model, the effects of low, moderate, and high chronic GH on fatty acid composition were determined for adipose and hepatic tissue and the metabolites of 20:4n-6 (arachidonic acid) were characterized to identify metabolic targets of action of elevated GH. The products of Δ-9 desaturase in hepatic, but not adipose, tissue were reduced in response to elevated GH. Proportional to the level of circulating GH, the products of Δ-5 and Δ-6 were increased in both adipose and hepatic tissue for the omega-6 lipids (e.g., 20:4n-6), while only the hepatic tissues showed an increase for omega-3 lipids (e.g., 22:6n-3). The eicosanoids, PGE2 and 12-HETE, were elevated with high GH but circulating thromboxane was not. Hepatic PTGS1 and 2 (COX1 and COX 2), SOD1, and FADS2 (Δ-6 desaturase) mRNAs were increased with elevated GH while FAS mRNA was reduced; SCD1 (ste-aroyl-coenzyme A desaturase) and SCD2 mRNA did not significantly differ. The present study showed that GH influences the net flux through various aspects of lipid metabolism and especially the desaturase metabolic processes. The combination of altered metabolism and tissue specificity suggest that the regulation of membrane composition and its effects on signaling pathways, including the production and actions of eicosanoids, can be mediated by the GH regulatory axis.

Growth Hormone Secretagogue (A233) Improves Growth and Changes the Tissue Fatty Acid Profile in Juvenile Tilapia (Oreochromis niloticus)

“…In our study, tilapia fed with the A233 supplemented diet also showed a significantly lower content of 18:1n‐9 (principal MUFA) in both liver and muscle; moreover, the total MUFA level was statically lower in this group. A similar pattern was observed for the hepatic lipid profile of GH transgenic mice, where the activity of Δ‐9 desaturase was found to decrease in response to a high level of circulating GH, as indicated by the decreased level of lipid (Oberbauer et al, ).…”

“…In GH transgenic mice, a high level of circulating GH changes the FA composition toward a more unsaturated profile (Oberbauer et al, ), reduced essential precursors of long‐chain PUFA (LN and ALA), and increased levels of desaturation and elongation products ARA and DHA, indicating increased activity of the D5D and D6D enzymes (Murray et al, ). In our study, the EPA, DPA, and DHA content and composition increased in both liver and muscle, possibly related to a higher level of circulating GH due to the inclusion of A233 in the diet.…”

“…GH‐treated transgenic fish have allowed studies on the effects of GH on the fatty acid (FA) profile and content in fish (Sugiyama et al, ). The regulation of the lipid profile and polyunsaturated fatty acid (PUFA) desaturases has been studied in various transgenic mouse models (Murray, Oberbauer, Sharp, & German, ; Oberbauer, German, & Murray, ), but not in fish.…”

“…Fatty acid synthesis of n‐3 and n‐6 LC‐PUFA in vertebrates is principally achieved by the incorporation of their respective dietary precursors, namely alpha linolenic (18:3n‐3, ALA) and linoleic (18:2n‐6, LNA) acid (Burdge & Calder, ; Goyens, Spilker, Zock, Katan, & Mensink, ; Sprecher, Luthria, Mohammed, & Baykousheva, ), through successive desaturation and elongation steps (Cook & McMaster, ; Park, Kothapalli, Lawrence, Tyburczy, & Brenna, ). High levels of circulating GH increase the products of Δ5 and Δ6 desaturase enzymes (D5 and D6D, respectively) in both adipose and hepatic tissue for the n‐6 PUFA (ARA), while only the hepatic tissues showed an increase for n‐3 PUFA (DHA) (Cook, McNiven, Richardson, & Sutterlin, ; Murray et al, ; Oberbauer et al, ).…”

Gene Expression Signature in Adipose Tissue of Acromegaly Patients

“…SCD products and FADS2 mRNA have also recently been shown to be induced by GH in mice [44]. The change in expression of these enzymes could be a possible link between acromegaly and insulin resistance due to an elevation of unsaturated fatty acids, as activity of FADS1 and FADS2 are associated with metabolic syndrome [45,46].…”