SUMMARY

The effects of oestrogens, testosterone, thyroxine, avian and mammalian gonadotrophins and of fasting, on the plasma free fatty acid (FFA) levels in the domestic fowl were investigated. Oestrogen treatment increased the levels of plasma FFA simultaneously with those of the total lipids and lipophosphoprotein in the immature fowl. Testosterone and thyroxine decreased the levels of plasma lipids and of lipophosphoprotein in the laying fowl, but had no effect upon the levels of plasma FFA in either the immature or laying fowl. Gonadotrophins were without effect upon the plasma FFA in the immature pullet but increased the levels in laying or moulting birds, the increases being accompanied by marked follicular growth. Fastings increased the level of plasma FFA in immature birds, but decreased the levels of FFA and total lipid in laying birds. Injections of large doses of hog anterior pituitary extract were without effect on the plasma FFA in conscious immature pullets but induced marked increases in the plasma FFA and a gross lipaemia in the rabbit. It is considered that the increases in plasma FFA found when the bird comes into lay are an indirect result of ovarian stimulation by pituitary hormones.

Dietary polyunsaturated fatty acid (PUFA) intake in humans can affect the incidence of a variety of diseases including coronary heart disease. Feeding high PUFA diets to cows can alter the PUFA content of milk for human consumption. PUFAs supply the precursors for prostaglandin (PG) synthesis and PGs in turn influence many aspects of reproduction. This study examined the effects of a control (CONT), a high n-6 PUFA diet (derived from protected soya) and a high n-3 diet (derived from protected linseed) on uterine PG synthesis in the lactating dairy cow. Endometrial explants obtained on days 15-17 of the oestrous cycle were cultured for an initial 42 h in vitro in fully defined medium (basal production) and then challenged with control medium, oxytocin (OT; 20 or 200 nM) or calcium ionophore A23187 (CaI; 10 microM). PGF(2 alpha), PGE(2) and 6-keto-PGF(1 alpha) were measured in the spent medium. The experiments were repeated using tissue from two groups of cows, nine in Experiment 1 (three cows per diet) and seven in Experiment 2 (four CONT and three n-6). Results of the two experiments were consistent. The basal concentrations of all three PGs were significantly lower (>50% reduction) in the n-6-fed group in comparison with CONT and n-3 groups. The n-3 diet did not alter basal PGF(2 alpha) and PGE(2) but increased 6-keto-PGF(1 alpha). The n-6 diet also inhibited the ability of the tissue to respond to both OT and CaI, with significant reductions in the stimulated levels of all three PGs. In contrast, the n-3 diet only had minor effects; it did not alter the response to OT but did reduce the long-term response to CaI at 24 h post treatment. In conclusion, dietary PUFA intake can inhibit PG production in bovine endometrial explants, with a more pronounced effect following n-6 rather than n-3 supplementation. These data suggest that a high n-6 diet reduces the endometrial capacity to produce PGs and may therefore have implications for the control of luteolysis and other PG-mediated events such as ovulation.

ABSTRACT

The effects of plasma free fatty acids (FFA) and somatostatin-14 (S-14) on concentrations of plasma GH, glucagon and insulin were investigated in juvenile ducks. Oleic acid, S-14 or both were infused into 4- to 7-week-old birds and plasma GH, glucagon-like immunoreactivity (GLI), immunoreactive insulin (IRI) and FFA were measured.

An increase in plasma GH and a decrease in GLI but no change in IRI was observed after infusion of 9 mg oleic acid/kg per min. A decrease in plasma GH, FFA and IRI and an increase in plasma GLI was seen after infusion of 800 ng S–14/kg per min. These effects of S-14 on IRI and GLI were abolished when S-14 was infused simultaneously with oleic acid.

It is concluded that FFA have a direct stimulatory effect on GH secretion and an inhibitory effect on glucagon secretion. Somatostatin-14 directly inhibits the secretion of GH and its stimulatory effect on the secretion of glucagon is mediated by a depression in concentrations of plasma FFA. Finally, S-14 has no effect on plasma insulin when basal levels of plasma FFA are maintained.

J. Endocr. (1985) 106, 21–25

We investigated the effect of n-6 polyunsaturated fatty acids (PUFAs) on prostaglandin (PG) production by the uterus. A mixed population of endometrial cells (epthelium and stroma) from late-gestation ewes were cultured in defined medium containing linoleic acid (LA, 18:2, n-6), gamma-linolenic acid (GLA, 18:3, n-6) or arachidonic acid (AA, 20:4, n-6) in concentrations of 0 (control), 20 or 100 microM. After 45 h in test medium with or without added PUFAs, cells were challenged with control medium (CM), oxytocin (OT, 250 nM), lipopolysaccharide (LPS, 0.1 micro g/ml) or dexamethasone (DEX, 5 microM) for 22 h in the continued presence of the same concentration of PUFA and the medium was collected for measurement of PGF(2alpha) and PGE(2). Supplementation with LA inhibited the production of PGF(2alpha) but did not alter PGE(2), whereas GLA and AA increased production of both PGs. All PUFA supplements thus increased the ratio of PGE(2) to PGF(2alpha) (E:F ratio) two- to threefold. In control cells, OT and LPS challenges stimulated the production of PGF(2alpha) and PGE(2). In all challenge groups, the concentrations of PGF(2alpha) in response to PUFAs followed the same pattern - LA<control<;GLA<AA - but there were significant alterations in responsiveness as a result of PUFA treatment. In the cells supplemented with 100 microM AA, there was no further increase in PGF(2alpha) output in the presence of OT or LPS and when 100 microM GLA was present neither LPS nor OT stimulated PGE(2) significantly. When LPS was given to AA-supplemented cells, the E:F ratio was increased. DEX did not change PGE(2) production in control or LA-treated cells, but the cells produced significantly less PGF(2alpha), so the E:F ratio was increased. In contrast, in GLA- and AA-treated cells, DEX reduced the production of both PGF(2alpha) and PGE(2), so the E:F ratio was unaltered. In summary, the study showed altered production of PGs in the presence of different PUFAs according to their position in the n-6 metabolic pathway. The type of PUFA present affected responsiveness to OT, LPS and DEX and also changed the ratio of PGE(2) to PGF(2alpha) produced. The possible implications of this work are discussed in relation to the effect of diet on term and pre-term labour, which both require upregulation of the endometrial PG synthetic pathway.

ABSTRACT

Intravenous injection of 8·5 nmol (1–24)ACTH increased the plasma levels of glucagon, insulin, glucose and free fatty acids in rabbits. The (1–24)ACTH-induced hyperglucagonaemia and hyperinsulinaemia started 3 and 20 min after the injection respectively. Similar increases in the plasma levels of glucagon, insulin and free fatty acids were found with 5·3 nmol (1–39)ACTH, whereas (1–4)ACTH, (4–10)ACTH, (1–10)ACTH, (11–24)ACTH, (7–38)ACTH and (18–39)ACTH (corticotrophin-like intermediate lobe peptide) injected at doses of approximately 8 nmol were inactive. Infusions with the alpha-adrenergic blocking drug, phentolamine, reduced the (1–24) ACTH-induced hyperglucagonaemia and hypergly-caemia, and augmented the (1–24)ACTH-induced hyperinsulinaemia, which now became significant after 5 min. Infusions with the beta-adrenergic blocking drug, propranolol, did not diminish the (1–24)ACTH-induced effects, but killed the rabbits after 2–4 h.

It is concluded that the acute in-vivo effects of ACTH in rabbits are modulated by the involvement of alpha-adrenergic receptors, which increased the plasma levels of glucagon and glucose, and delayed and diminished the ACTH-induced increases in the plasma levels of insulin. The (1–24)ACTH-induced increases in the plasma levels of free fatty acids were not influenced by the adrenergic blocking drugs.

J. Endocr. (1984) 100, 345–352

SUMMARY

The level of plasma free fatty acids (FFA) in both laying and immature non-laying hens was not markedly decreased by intravenously injected amounts of glucose sufficient to double the level of plasma glucose for 15–30 min. This was true for fasting and for fed birds. Adrenocorticotrophic hormone (ACTH) given i.v. to laying birds produced a definite increase in the levels of plasma FFA and glucose in doses of 60 i.u./kg. Daily doses of long-acting ACTH given i.m. for 3 days to laying birds produced a marked increase in plasma glucose accompanied by a pronounced fall in plasma FFA. Insulin markedly lowered the plasma glucose level in both mature and immature birds and caused a large and immediate increase in plasma FFA. Glucagon also induced a marked increase in plasma FFA accompanied by a rise in plasma glucose. The effects of insulin and glucagon were not abolished by pretreating the birds with reserpine or hexamethonium bromide. It is concluded that the effect of glucagon on plasma FFA is probably a result of a direct action on avian adipose tissue and that insulin may promote a similar response by an increased release of glucagon from the pancreas.

SUMMARY

The effects of adrenaline, noradrenaline, corticotrophin (ACTH), cortisol and corticosterone on the levels of blood lipids have been studied in dogs and rats. Blood glucose, plasma free fatty acids (FFA) and corticosteroids were determined 4 hr. after injection. Plasma cholesterol, phospholipids and triglycerides were determined 24 hr. after the last of three daily treatments. In some experiments an oral glucose load was given at the same time as the hormones. In dogs plasma FFA were increased by adrenaline and noradrenaline, decreased by ACTH plus glucose and not affected by ACTH alone. Gradual rises in the lipoprotein levels of dogs were produced by any of the hormones given and followed acute rises in corticosteroid concentration regardless of the acute changes in plasma FFA. In rats plasma FFA were increased by adrenaline and ACTH, decreased by glucose and not affected by ACTH plus glucose. It was not possible to produce rises in lipoprotein by administering adrenaline or ACTH to rats. Exogenous corticosteroids produced increases in the cholesterol and phospholipid levels. The effects of corticosterone were potentiated by oral glucose but cortisol produced a full effect without extra glucose. The FFA responses to subcutaneous adrenaline in rats were reduced by adrenalectomy, but the increases in plasma FFA produced by intravenous infusion of adrenaline or ACTH were similar in adrenalectomized and intact rats. It was concluded that changes in lipoproteins are not causally related to increased mobilization of FFA but are dependent on increased adrenocortical hormone secretion in the presence of excess carbohydrate.

To determine whether volatile fatty acids (VFA) are involved in the regulation of plasma concentrations of insulin or glucagon in the goat, VFA, separately or in combination, were administered into the jugular vein, the portal vein or the rumen, and their effects on pancreatic hormones as well as on VFA measured in venous blood. Propionate, n-butyrate and n-valerate, but not acetate, injected in pharmacological doses, were potent stimuli not only of the secretion into the plasma of insulin but also of glucagon. As regards insulin, the response to VFA was probably not mediated to an appreciable extent by glucose or glucagon. β-Hydroxybutyrate did not mediate the effect of n-butyrate on insulin and glucagon. The effects of VFA appear to be peculiar to the ruminant since in the rat injection of similar doses resulted in either no changes or very small changes of plasma insulin and glucagon.

Intraportal infusions over 4 h of mixtures of VFA, resulting in less extreme, more physiological blood concentrations of VFA, elicited sudden transient increases in insulin and to a lesser extent in glucagon. After these peaks insulin and glucagon declined to preinfusion levels and remained virtually unaltered during the remainder of the infusion in spite of sustained, raised concentrations of VFA in the peripheral circulation. These results suggest that under these conditions the rate of increase of VFA is a signal for the secretion of pancreatic hormones. Intraruminal infusions, representing a more physiological route of administration, of single VFA at high rates resulted in a small increase in insulin for propionate infusion only, whereas a mixture of VFA at a physiological rate induced barely any change in insulin or glucagon. It is concluded that under physiological conditions the rate of increase of VFA may contribute to the insulin secretion in the free-feeding goat, but it is unlikely that VFA are the sole controlling agents of insulin release. It is even less probable that the release of glucagon is governed by VFA in the free-feeding goat.

SUMMARY

The relationships between plasma insulin, glucose, non-esterified fatty acid (NEFA) and α-amino nitrogen concentrations in the domestic fowl have been studied. During a 72-hr. fast the plasma glucose concentration fell while the NEFA concentration rose but there was no change in plasma insulin concentration. Both oral and intracardiac glucose increased the plasma insulin concentration and lowered the plasma NEFA and α-amino nitrogen concentrations. Oral amino acids increased plasma insulin and glucose concentrations but had no effect on plasma NEFA. Intracardiac ox insulin depressed plasma glucose and α-amino nitrogen and increased the plasma NEFA concentration. Intracardiac glucagon increased both plasma glucose and NEFA and depressed the plasma α-amino nitrogen concentrations but had no significant effect on plasma insulin. Intracardiac adrenaline had no effect on plasma NEFA but increased plasma glucose concentration and caused a small depression in plasma insulin concentration.

We investigated the effect of fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, on insulin sensitivity including lipid metabolism in skeletal muscle. Six-week-old male Sprague-Dawley rats were divided into two groups: those fed a standard chow (control) or a fructose-rich chow (fructose-fed rats (FFRs)) for 6 weeks. FFRs were treated either with a vehicle or with 30 mg/kg per day of fenofibrate for the last 2 weeks. Insulin sensitivity (M-value) was estimated by the euglycemic hyperinsulinemic glucose clamp method. Fatty acid-binding protein (FABP) in skeletal muscle was measured by ELISA, and the expression of FABP mRNA was analyzed by semi-quantitative RT-PCR. The serum and muscle triglyceride (sTG and mTG) levels and the activity of 3-hydroxyacyl-CoA dehydrogenase (HADH), a beta-oxidation enzyme, in muscle were also determined. FFRs showed a lower M-value and higher blood pressure, sTG and mTG than did the control group. The mTG was correlated positively with sTG and negatively with the M-value. Fenofibrate treatment for 2 weeks did not change blood pressure but significantly improved the M-value, sTG and mTG. FABP content and mRNA in the soleus muscle were significantly elevated in FFRs compared with those in the control group. Fenofibrate treatment further increased FABP. The HADH activity was comparable between the control group and FFRs, but significantly increased by fenofibrate treatment. These results suggest that fenofibrate improves insulin sensitivity not only by lowering serum lipids and subsequent influx of fatty acids into muscles but also by reducing intramuscular lipid content via further induction of FABP and stimulation of beta-oxidation in muscles.