Increase In Free Fatty Acid Concentration Research Articles

Hormonal and metabolic responses to repeated cycling sprints under different hypoxic conditions

ObjectiveSprint exercise and hypoxic stimulus during exercise are potent factors affecting hormonal and metabolic responses. However, the effects of different hypoxic levels on hormonal and metabolic responses during sprint exercise are not known. Here, we examined the effect of different hypoxic conditions on hormonal and metabolic responses during sprint exercise. DesignSeven male subjects participated in three experimental trials: 1) sprint exercise under normoxia (NSE); 2) sprint exercise under moderate normobaric hypoxia (16.4% oxygen) (HSE 16.4); and 3) sprint exercise under severe normobaric hypoxia (13.6% oxygen) (HSE 13.6). The sprint exercise consisted of four 30s all-out cycling bouts with 4-min rest between bouts. Glucose, free fatty acids (FFA), blood lactate, growth hormone (GH), epinephrine (E), norepinephrine (NE), and insulin concentrations in the HSE trials were measured before exposure to hypoxia (pre 1), 15min after exposure to hypoxia (pre 2), and at 0, 15, 30, 60, 120, and 180min after the exercise performed in hypoxia. The blood samples in the NSE trial were obtained in normoxia at the same time points as the HSE trials. ResultsCirculating levels of glucose, FFA, lactate, GH, E, NE, and insulin significantly increased after all three exercise trials (P<0.05). The area under the curve (AUC) for GH was significantly higher in the HSE 13.6 trial than in the NSE and HSE 16.4 trials (P<0.05). A maximal increase in FFA concentration was observed at 180min after exercise and was not different between trials. ConclusionThese findings suggest that severe hypoxia may be an important factor for the enhancement of GH response to all-out sprint exercise.

The metabolic profile of growing lambs fed diets rich in unsaturated fatty acids

The effect of two diets enriched with unsaturated fatty acids--one containing the addition of dried distillers grains with solubles (DGS) and the other the addition of false flax--Camelina sativa cake (CS)--on some metabolic parameters and hormone concentration in growing lambs was determined in this experiment. A total of 21 ram lambs of the Polish Whiteheaded mutton sheep were divided into three groups (the control, receiving DGS and CS). The diets were administered to animals for 6 weeks. During the experiment, peripheral blood was collected. Glucose (GL), total cholesterol (CH), triglycerides (TG), free fatty acids (FFA), insulin (IN), leptin (LE), triiodothyronine (T3) and thyroxine (T4) were assayed in serum. The age-dependent reduction in CH and TG limited by both experimental diets were observed. A significant increase in FFA concentration was observed in samples collected in the last, that is, third, time period. This was most probably caused by a 12-h pre-slaughter fasting period. A significantly lower dynamic of FFA increase in that experimental period was found in animals receiving the experimental feed. Insulin concentration in DGS-receiving lambs was increased, in contrast to the CS-receiving lambs, in which it was lower when compared to the control. LE concentration was decreased by both experimental diets, more markedly in the DGS-receiving animals. No differences between the experimental groups and the control were observed in T3 and T4 concentrations. The effect of 12-h pre-slaughter fasting was statistically highly significant for the levels of examined blood markers and hormones, except for TG and IN in the group of lambs receiving the experimental diet with CS.

Elevated Free Fatty Acid is Associated with Cardioembolic Stroke Subtype

Free fatty acids (FFAs), an important energy substrate, have an association with cardiovascular diseases, such as atherosclerosis, myocardial dysfunction and abnormal cardiac rhythm. However, limited reports are available on the association between FFAs and ischemic stroke. We hypothesized that plasma FFA concentration could be associated with an ischemic stroke, emphasizing the relationship between FFA and subtypes of ischemic stroke. A cross-sectional study examined the association between FFA concentration and subtypes of stroke and cerebral atherosclerosis from a hospital-based acute stroke registry. Data of 715 stroke patients were analyzed. The concentration of FFA was highest in the cardioembolic stroke subtype compared with the other stroke subtypes. Logistic regression analysis revealed that an increase in FFA concentration was significantly associated with the cardioembolic subtype after the adjustment of covariates. FFA concentration was also higher in patients with atrial fibrillation (AF) than those without AF. According to the presence of atherosclerotic stenosis, no significantly difference of FFA concentration was found for intracranial and extracranial cerebral arterial atherosclerosis. Here we report a significant association between fasting FFA concentration and the cardioembolic stroke subtype. AF is suggested as the mediating factor between FFA and the cardioembolic stroke subtype.

Influence of free fatty acids, sterols and phospholipids on volatile compounds in olive oil headspace determined by solid phase microextraction-gas chromatography

In order to study the influence of some polar compounds, naturally present in virgin olive oils (VOOs), on the volatiles release, the volatiles-free olive oil matrix was enriched with free fatty acids (FFA) (concentration range from 0.35 to 1.40 g/100 g), sterols (1.0–2.5 g/kg) and phospholipids (1.6–6.0 g/kg). Sixteen standards of VOO aroma compounds were dissolved in thus obtained olive oil matrices. Volatile compounds were analysed by headspace solid phase microextraction with DVB/CAR/PDMS fibre and gas chromatography with flame ionization detection. Evaluation of the data by statistical analysis revealed that FFA, sterols and phospholipids, in concentration ranges considered in this study, generally did not significantly influence the determination of VOO volatiles. The most important changes occurred in the release of the three alcohols (Z-2-penten-1-ol, 1-hexanol and E-3-hexen-1-ol) and 3-methylbutyl acetate which slightly decreased upon the increase of FFA concentration.

Extrusion deactivation of rice bran enzymes by pH modification

Rice bran is considered in Mexico as “waste”, useful only for feeds. As considerable amounts of oil are available in rice bran, it might be worthwhile to stabilize it and extract the edible oil before using it for feedstuffs. Precisely these oils are responsible for rice bran rapid deterioration, particularly in climatic conditions such as those prevalent in Mexico's tropical areas (high humidity and high temperature). This paper deals with the study of the effect of pH during extrusion of fresh rice bran in order to inactivate lipid-breaking enzymes. Hydrochloric acid or calcium hydroxide, Ca(OH)2, were added at 0, 1, 5, 10% (dry basis), and moisture content of the bran samples was varied (20, 30, 40%, dry basis) in a 32 factorial design to corroborate its effect at acid and alkaline pH range. Free fatty acids (FFA) increase was the control variable. Extruded samples were stored at room temperature (between 20 and 28 °C) using a non-extruded sample as control to assess the shelf life effects. Results indicate that in acid-extruded samples, the increase in FFA concentration after 98 days was much less than in the unmodified-pH or alkaline samples. The lowest FFA increase after 3 months of storage time was <10 mg FFA/g rice bran using extrusion with no water or chemicals added or using extrusion adding HCl, irrespective of the moisture content of rice bran.

Effect of cow diet on free fatty acid concentrations in milk

Two experiments were conducted: one during summer 1999 (Experiment 1, 180–200 days in milk (DIM)) and one in autumn 1999 (Experiment 2, 220–250 DIM), to examine the effect of pasture allowance on the formation of free fatty acids (FFA) in milk from multiparous Jersey cows. In Experiment 1, three treatments were investigated (n = 15): fully fed on pasture (FFP) (pasture allowance 36 kg DM/cow per day), restricted pasture (RP) (pasture allowance 23 kg DM/cow per day), and RP plus 5 kg DM/cow per day of pasture silage (RP+S). Treatments were applied for 21 days. Experiment 2 ran for 14 days and comprised two treatments, (n = 15) FFP (pasture allowance 38 kg DM/cow per day) and a more restricted pasture allowance (RP), of 16 kg DM/cow per day. Milk samples for FFA analyses were collected by hand milking each cow during the morning milking. The sample was split into three subsamples: Sample 1 was fixed to prevent any further lipolysis (L0), Sample 2 had no additive (L24), and for Sample 3 air was drawn through the sample for 4 min (D24). All samples were stored at 4°C for 24 h before being analysed for FFA concentrations by the Bureau of Dairy Industries (BDI) method. A restricted pasture allowance (RP) reduced milk yield by 14 and 36% in Experiments 1 and 2, respectively. The feeding of silage to cows on a restricted pasture allowance had no effect on milk yield. Pasture allowance or supplementary feeding in Experiment 1 had no effect on total FFA concentrations in L0, L24, or D24 samples. However, the increase in FFA during 24 h, storage (L24‐L0) was greater (P < 0.001) for the RP and RP+S than the FFP treatments. The restricted pasture allowance in Experiment 2 caused an increase in total FFA concentrations in the L24 (P < 0.001) and D24 (P < 0.05) samples. The increase in FFA concentration during storage (L24‐L0) was greater (P < 0.001) in milk from the RP treatment. In both trials, the increase in FFA concentrations over 24 h between damaged and undamaged milk (D24‐L24) was similar for each treatment. The greater increase in FFA concentration was in undamaged milk (L24‐L0) from the RP treatments. From this observation it is hypothesised that the increase in FFA concentrations in milk due to underfeeding resulted from an increase in the activity of lipoprotein lipase and not from an increased susceptibility of the milk fat globule membrane to damage. Overcoming a restricted pasture allowance by supplementary feeding of silage had little effect on reducing the impact of arestricted availability of summer pasture on milk yield or FFA concentrations.

Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects.

To test the possible acute proinflammatory effects of fatty acids, we induced an increase in plasma free fatty acid (FFA) concentrations after a lipid and heparin infusion for 4 h in 10 healthy subjects. We determined the nuclear factor-kappaB (NF-kappaB) binding activity in mononuclear cells (MNCs), the p65 subunit of NF-kappaB, reactive oxygen species (ROS) generation by MNC, and polymorphonuclear leukocytes (PMN). Brachial artery reactivity, using postischemic flow-mediated dilation, was also measured. NF-kappaB binding activity in the MNC nuclear extracts increased to 163 +/- 17% and 144 +/- 14% as compared with basal levels at 2 and 4 h (P < 0.005) and remained elevated (P < 0.05) at 6 h (2 h after cessation of lipid infusion). NF-kappaB p65 subunit protein expression in MNC homogenates also increased at 2, 4, and 6 h (P < 0.05). ROS generation by PMNs increased significantly at 2 and 4 h (P < 0.005), whereas that by MNCs increased at 4 h (P < 0.05). Plasma macrophage migration inhibitory factor increased at 2 (P < 0.05) and 4 h (P < 0.005), respectively, and declined to baseline at 6 h. The postischemic flow-mediated dilation of brachial artery decreased from 6.3 +/- 1.1% at baseline to 4.3 +/- 1.9% and 2.7 +/- 2.1% (P < 0.01) at 2, 4, and 6 h, respectively. We conclude that an increase in FFA concentration induces oxidative stress and has a proinflammatory effect; it also impairs postischemic flow-mediated vasodilation of the brachial artery.

Changes in free fatty acids during ripening of Teleme cheese made with ewes’, goats’, cows’ or a mixture of ewes’ and goats’ milk

Lipolysis was studied in Teleme cheeses manufactured from ewes’ milk, goats’ milk, cows’ milk and a mixture of ewes’ and goats’ milk. Changes in the profiles of free fatty acids (FFAs) extracted from the cheeses were followed using gas chromatographic techniques up to 180 d of ripening. Evolution of lipolysis was also monitored following acid degree value (ADV). It was found that the ADVs of cows’ milk Teleme cheeses were significantly ( P <0.05) higher at 1 and 60 d of ripening than those of cheeses made from ewes’, goats’ or the mixed milk. The degree of lipolysis was shown by the increase in concentration of FFAs during ripening. A low total FFA value characterized all Teleme cheeses. The most abundant FFAs in ripened cheeses were palmitic and oleic acids. In all types of cheeses the concentration of acetic acid increased rapidly in the first period of ripening and storage, reaching its maximum values at approximately 60 d ripening. Total amounts of FFAs at all ripening times examined were significantly ( P <0.05) higher in cheeses made from cows’ milk.

Age-Related Changes in Valproic Acid Binding to Rat Serum Proteins in Vitro

AbstractThe effect of age on the in vitro binding of valproic acid (VPA) to serum proteins was investigated in rats ranging in age from 14days (preweanling) to 24months (senescent). The influence of free fatty acid (FFA) and total protein (TP) concentrations on age-related changes in binding was examined. The protein binding of VPA was altered during development and aging. The VPA fraction unbound (fu) at low VPA concentrations was significantly higher in older age groups (12 and 24months old; fu=0.26–0.30) than in younger animals (14, 20, and 40days old; fu=0.16–0.18). Binding was best described by a model incorporating a saturable and a nonsaturable binding site. Binding affinity at the saturable binding site was lowest at the extremes of age. Changes in binding at either the saturable or the nonsaturable site were not predicted by changes in TP or FFA with age. Changes in nonsaturable binding were marginally associated with age (p=0.0952). A 3-fold increase in FFA concentrations was necessary to produce a 1.5-fold increase in VPA fu. There was less than a 2-fold difference in FFA concentrations between the age groups (range 0.219–0.379mmol/L). Thus, the difference in FFA concentrations between the age groups may not have been large enough to cause measurable differences in displacement of VPA from binding sites. Changes in protein binding may contribute to age-related changes in disposition of VPA observed in the rat. Changes in the serum concentrations of specific FFA or proteins may play a role in the altered VPA binding with age, but changes in total FFA or protein concentrations do not account for the age-related differences observed. Further investigation is required to identify the mechanism(s) responsible for age-related changes in binding of VPA to serum proteins measured in vitro.

Disappearance of palmitic acid from plasma of fetal and newborn sheep.

These studies were undertaken to measure the kinetic constants that characterize the disappearance of a representative free fatty acid (FFA) from the plasma of fetal and newborn sheep. A bolus of albumin-complexed [14C]palmitic acid was infused intravenously, and during the next 8 min, 24 arterial samples were collected to characterize the disappearance curve. Palmitic acid disappearance from plasma was well described by a double-exponential model. When birth was simulated in utero, kinetic values were not changed by cooling. However, after intrauterine ventilation with O2, the volume of distribution of the FFA increased 29%, its plasma clearance rate decreased 26%, and its apparent half-life in the plasma lengthened from 0.8 to 1.2 min (all P < 0.01, n = 8). After umbilical cord occlusion, plasma clearance rate decreased a further 19% and half-life lengthened to 1.4 min. About 60% of the increase in FFA concentration during simulated birth is explained by increased release from adipose stores, and 40% is explained by decreased clearance. Further experiments tested the influence of FFA concentrations themselves. After infusion of unlabeled FFA, clearance of the tracer decreased 23% (P < 0.05, n = 5), a result consistent with a saturable membrane transporter of FFAs.

Gastrointestinal motility and plasma hormone and metabolite responses to acute cold stress and somatostatin-14 in sheep

Effects of intrajugular infusions of somatostatin-14 (SS-14) (8.9, 18.4, and 37.3 ng min−1 kg−1 BW) or saline were studied in three acutely (2 h) cold-stressed (0 °C) ewe lambs (39.8 ± 1.8 kg BW) fed a barley soybean meal diet at 25.6 g DM d−1 kg−1 BW. Acute cold exposure transiently increased (P &lt; 0.001) and rewarming decreased (P &lt; 0.001) recticular contraction frequency, with no effect of SS-14. The duration of duodenal irregular spiking activity was decreased (P &lt; 0.05) by SS-14 at doses of 18.3 and 37.3 ng min−1 kg−1 and was not affected by cold exposure. This resulted in a decrease (P &lt; 0.05) in the average duration of the individual migrating myoelectric complex. Cold exposure increased (P &lt; 0.01) plasma concentration of free fatty acids (FFA). Orthogonal contrasts of the changes during somatostatin infusion indicated linear increases in glucose and linear and cubic increases in FFA concentrations in plasma (P &lt; 0.05). Infusion of somatostatin had no effect on basal concentrations of growth hormone, insulin, or glucagon but produced linear reductions in plasma insulin and glucagon responses during cold exposure (P &lt; 0.05). Somatostatin modestly influenced hormone and metabolite concentration during acute cold exposure without apparent effect on body temperature. Key words: Cold, somatostatin, sheep, gastrointestinal motility, glucagon, insulin

Physiologic Responses of Elite Paraplegic Road Racers to Prolonged Exercise

The purpose of this study was to determine cardiopulmonary and selected metabolic responses in spinal cord injured (SCI) paraplegics during prolonged arm crank exercise (ACE). Six male and one female elite SCI paraplegic (T4-12 lesions) road racers performed 40 continuous minutes of ACE at 60% of peak ACE oxygen uptake (VO2). Blood samples (30 ml) were collected via antecubital venipuncture at rest and minutes 20 and 40 of ACE for determinations of hemoglobin, hematocrit, serum free fatty acid (FFA), and blood lactate (LA) concentrations. No significant differences were observed over time for VO2 or pulmonary ventilation. Heart rate recorded at minutes 30 and 40 was significantly elevated above HR at minutes 10 and 20 of ACE indicating the presence of an upward drift in HR in paraplegics performing prolonged ACE. Compared to rest, LA concentration was significantly higher at minute 20 and remained relatively stable thereafter. A significant increase in FFA concentration at minute 40 combined with a significant decline in the respiratory exchange ratio suggested a preference for lipid substrate utilization by exercising muscle as ACE continued. The data indicate that the autonomic sympathetic nervous system impairment associated with paraplegia had no apparent adverse effects on cardiopulmonary or metabolic adjustments to prolonged ACE in these well-trained subjects.

Protein Binding of Antiepileptic Drugs During Pregnancy, Labor, and Puerperium

Twenty-four epileptic women were followed-up during late pregnancy, labor, and early puerperium in order to detect possible alterations in serum protein binding of antiepileptic drugs (AEDs). The total and free concentrations of carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA) in maternal serum were measured. In addition, the concentrations of albumin, alpha 1-acid glycoprotein (AGP), and free fatty acids (FFA) were also measured. Total AED concentrations during labor were influenced by changes in drug dosages; total PHT increased during the first puerperal weeks. During labor the free fraction of CBZ remained stable, whereas PHT and particularly VPA free fractions increased. This phenomenon was parallel to the increase in FFA concentration; FFA concentrations decreased again during the first days postpartum. Albumin and AGP concentrations were low during pregnancy and labor, and increased after delivery. The total umbilical CBZ and PHT concentrations were not significantly different from maternal concentrations. The total VPA concentration in umbilical serum was significantly higher than that in maternal serum. The free fraction of CBZ was higher and that of PHT and VPA lower in umbilical than in maternal serum at delivery. Umbilical cord serum had a higher albumin but a lower AGP and FFA concentration than maternal serum. The changes in PHT and particularly VPA free fraction associated with changes in FFA concentration should be considered when assessing the total concentration of these drugs in maternal and umbilical serum.

The effect of free fatty acids on insulin-mediated glucose uptake.

Free fatty acids (FFA) have been shown in vitro to inhibit insulin-mediated glucose uptake by muscle and have been proposed as in vivo mediators of peripheral insulin resistance. Twenty percent fat emulsion and heparin were administered to six awake healthy dogs during 3-hr insulin clamp studies. Lipid infusion resulted in a fivefold increase in FFA concentration over control (2371 +/- 331 vs 439 +/- 65, P less than 0.002), but did not importantly alter glucose and insulin concentrations. No change was observed in glucose disposal (13.30 +/- 1.41 vs 13.76 +/- 1.51 mg/kg . min control), hindquarter A-V glucose concentration difference (9 +/- 2 vs 9 +/- 1 mg/dl), or hindquarter glucose uptake (3.42 +/- 0.84 vs 3.71 +/- 0.65 mg/kg . min). These observations suggest that FFA may not be important mediators of peripheral insulin resistance in critically ill patients.

Glucose tolerance in viral hepatitis. A study of twenty patients during the acute phase and after recovery.

Twenty patients with viral hepatitis were investigated during the acute phase and after recovery in order to study their glucose tolerance. During hepatitis, three tests were performed: oral and intravenous glucose tolerance tests and tolbutamide test, with measurements of glucose, insulin, free fatty acids, trigiycerides, growth hormone, and cortisol. After recovery, a control oral glucose tolerance test was performed. All these results were compared with those of healthy controls. During the acute phase, both oral and intravenous glucose tolerance tests showed two groups of patients: nine with normal glucose tolerance but significant hyperinsulinism, and 11 with glucose intolerance but a delayed and not increased insulin response. Tolbutamide test was always normal, without any difference between these two groups. Free fatty acids (FFA) were increased only in the glucose-intolerant group; there was a significant negative correlation between basal FFA and the K values. Trigiycerides were increased in the two groups, but were higher in the normal glucose-tolerant one. Growth hormone and cortisol were increased only when the K value was very low. All these parameters returned to normal in all the patients after their recovery. Clinical features, hepatic tests, and HLA typing were similar in the two groups, with no significant differences. A comparative group of patients with mild and nonhepatic infections did not show any abnormalities. This study suggests there is a transitory insulin-resistant state during viral hepatitis, which can be due to an increase in FFA concentrations. Glucose intolerance occurs in half of the cases, possibly as a consequence of an additional β-cell impairment.

Free fatty acids in the early inflammatory papule of acne vulgaris.

Summary The role of free fatty acids (FFA) in the pathogenesis of acne is disputed. Several studies have failed to show an increase in FFA concentration in skin surface lipids (SSL) from acne patients. It has been suggested that a marked increase in FFA concentration in a single sebaceous follicle may lead to the inflammatory lesion in acne, and because SSL samples are usually taken from a large area, this localized increase would be swamped by the lipid from the surrounding normal follicles. We therefore used a micro-cylinder method to obtain SSL from early acne papules and we compared this with SSL from nearby ‘normal’ skin in 19 patients. The samples were analysed by quantitative thin layer chromatography. We found no significant difference in the mean FFA concentration in SSL obtained from acne papules and normal skin. Our findings do not support the idea that the inflammation of acne is due to an increase in FFA concentration in skin lipids.

METABOLIC EFFECTS OF CORTISOL, CORTICOSTERONE AND ADRENOCORTICOTROPHIN IN A PROTOTHERIAN MAMMAL TACHYGLOSSUS ACULEATUS (SHAW)

The effects of injections of cortisol, corticosterone and ACTH on indices of carbohydrate, fat and protein metabolism were investigated in the conscious echidna, Tachyglossus aculeatus. Intravenous infusion of cortisol and corticosterone for 2 h at rates of 3 and 30 microgram/kg/h respectively did not cause significant changes in the plasma concentrations of glucose, urea or amino acids during a 12.5 h observation period. In contrast, a dose-related increase in plasma free fatty acid (FFA) concentration was observed. Infusion of synthetic ACTH at 2 i.u./kg/h for 2 h caused a minor, short-lived increase in FFA concentration. Daily i.m. injections of 0.2 mg cortisol or corticosterone acetates/kg, which raised plasma total corticosteroid concentrations to levels characteristic of maximal ACTH stimulation, did not cause glycosuria nor was there any change in body weight, nitrogen intake or urinary nitrogen excretion. However, there was a minor, but significant, increase in plasma glucose concentration. The liver glycogen content of 24 h fasted, corticosteroid-treated animals was similar to that of fasted control animals. It is concluded that cortisol, corticosterone and ACTH have only minor effects on carbohydrate and protein metabolism and that the main action of these hormones may be to mobilize fat reserves.

The effect of maternal starvation on the metabolic response to cold of the newborn rabbit.

Acute starvation of the pregnant rabbit before delivery leads to lipid mobilization, the circulating concentrations of free fatty acids (FFA) increase, and more fatty acids cross the placenta and are stored as triglyceride in fetal tissues, particularly the liver and adipose tissue. Thus the newborns from these unfed does are born with larger fat stores than normal. In this investigation the responses of newborns of unfed and fed does were compared with respect to aspects of the metabolic responses to birth and subsequent cold exposure. It was found that at 2 hr of age the newborns of unfed does had higher circulating concentrations of FFA and triglycerides. The glucose and glycerol concentrations were similar in the two groups, but after 2 hr of cold exposure the newborns of fed does had much higher blood concentrations of both glucose and glycerol. In both, a large increase in FFA concentration was seen. The newborns of unfed and fed does had similar minimal metabolic rates, but the maximal rate of heat production was greater on average by 15% in the newborns of unfed does over the first 3 days of life. Maternal nutrition immediately before delivery has considerable effect on the circulating concentrations of metabolites and the responses to cold of the newborn.

Effect of fatty acids on thyroid function tests in vitro and in vivo

Addition of long-chain fatty acids to serum increased thyroxine (T 4), measured by a competitive protein binding assay, and triiodothyronine (T 3) uptake by Sephadex or resin (T 3U tests). This is compatible with the assumption that fatty acids compete with thyroxine for binding sites on T 4-binding proteins. When equimolar concentrations of various saturated and unsaturated fatty acids were added to serum it was observed that the effectiveness in raising tests based on protein binding of thyroid hormones increased with the number of double bonds. Unsaturated fatty acids also increased serum T 3 determined by radioimmunoassay (RIA). T 4(RIA) was not significantly influenced by either saturated or unsaturated fatty acids. Serum T 4(CPB) rose during storage at 22°C and 37°C but was stable at 4°C and — 20°C for periods up to two weeks. The proportional increase in T 4(CPB) and free fatty acids (FFA) indicated that this phenomenon was due, at least partly, to the interference from FFA formed during storage of the serum. There was also a small, significant increase in T 3U, T 3(RIA) and CT 4I (a free thyroxine estimate) after storage of serum at room temperature or higher for one to two weeks. Serum T 4(RIA) did not alter during two weeks of storage. In five subjects with raised serum FFA after eating a fat meal followed by a heparin injection an increase in T 4(CPB), T 3U, T 3(RIA) and CT 4I that was proportional to the increase in FFA was observed. This effect on the thyroid tests was small until the increase in FFA concentration exceeded 2 mmol/1. T 4(RIA) did not respond to the increase in FFA. In ten patients with raised levels of FFA due to uncontrolled diabetes T 4(CPB), T 4(RIA) and T 3(RIA) decreased while T 3U increased. These unexpected alterations were probably related to the severe, chronic illness in these patients. Increased FFA in vivo seem to be of little importance for the interpretation of thyroid tests in clinical practice.

Thyroid hormone-induced changes in body temperature and metabolism during exercise in dogs.

Changes in serum total thyroxine concentration (TT4) and the effects of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) injection on plasma free fatty acid (FFA) level and rectal temperature (Tre) responses were measured in six dogs at rest and during 1 h of submaximal treadmill exercise. At rest there were no increases in FFA level or Tre up to 72 h after thyroid hormone treatment. During exercise, 5 h after a single T4 injection (0.1 mg/kg), there was a) a significant increase in TT4, although the resting level was markedly elevated, and b) a significant increase in FFA concentration and Tre above control values. Seventy-two hours after T4 injection there was a similar increase in TT4 during exercise and both FFA and Tre levels were greater than 5-h values. The elevated Tre was not associated with increased plasma Na+, K+, or osmotic concentrations. Compared with T4 data, T3 injection (0.1 mg/kg) resulted in greater increases in FFA level and Tre during exercise; two animals reached 43.1 degrees C. There were no significant differences in the respiratory exchange ratio (R) or O2 uptake between the control and T3 experiments. It was concluded that thyroid hormones markedly enhance FFA mobilization and elevated Tre during exercise, but not a rest. The hyperthermic response appears to be due to an increase in the level of regulated body temperature rather than to a depression of heat dissipation.