Plasma Free Fatty Acid Responses Research Articles

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism. Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT. ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826±25 vs. 634±22μmol/L, P<0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT. ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.

Indispensable role of mitochondrial UCP1 for antiobesity effect of β3-adrenergic stimulation

Mitochondrial uncoupling protein-1 (UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy expenditure and adiposity. However, UCP1 knockout (KO) mice were reported to be cold intolerant but unexpectedly did not get obese even after hyperphagia, implying that UCP1 may not be involved in the regulation of adiposity. Treatment of obese animals with beta3-adrenergic agonists is known to increase lipid mobilization, induce UCP1, and, finally, reduce body fat content. To obtain direct evidence for the role of UCP1 in the anti-obesity effect of beta3-adrenergic stimulation, in the present study, UCP1-KO and wild-type (WT) mice were fed on cafeteria diets for 8 wk and then given a beta3-adrenergic agonist, CL-316,243 (CL), or saline for 2 wk. A single injection of CL increased whole body oxygen consumption and brown fat temperature in WT mice but not in KO mice, and it elicited almost the same plasma free fatty acid response in WT and KO mice. WT and KO mice increased similarly their body and white fat pad weights on cafeteria diets compared with those on laboratory chow. Daily treatment with CL resulted in a marked reduction of white fat pad weight and the size of adipocytes in WT mice, but not in KO mice. Compared with WT mice, KO mice expressed increased levels of UCP2 in brown fat but decreased levels in white fat and comparable levels of UCP3. It was concluded that the anti-obesity effect of beta3-adrenergic stimulation is largely attributable to UCP1, but less to UCP2 and UCP3, and thereby to UCP1-dependent degradation of fatty acids released from white adipose tissue.

Relationship between visceral fat accumulation and anti-lipolytic action of insulin in patients with type 2 diabetes mellitus.

Insulin resistance is closely related to developing type 2 diabetes mellitus. Visceral fat accumulation is associated with insulin resistance, which affects the free fatty acid (FFA) metabolism. We investigated the interactions among visceral fat accumulation, FFA metabolism and insulin resistance in 20 patients with type 2 diabetes mellitus, including 11 obese and 9 non-obese subjects. Body fat distribution was estimated by measuring the areas of both subcutaneous and visceral fat mass on abdominal computed tomography at the umbilical level. Glucose infusion rate (GIR) and plasma FFA responses to insulin were determined as an index of insulin resistance and anti-lipolytic action, respectively, in a euglycemic hyperinsulinemic clamp study. There was an inverse correlation between GIR and insulin-induced decrease in plasma FFA in all diabetic patients (r = -0.652, P < 0.01). Visceral fat mass area was well correlated with GIR (r = -0.583, P < 0.01) and insulin-induced decrease in plasma FFA (r = 0.724, P < 0.001), whereas subcutaneous fat mass area was not correlated either with GIR or plasma FFA decrease. These findings suggest that visceral fat accumulation results in increasing the resistance against the anti-lipolytic action of insulin, and that FFA metabolism is closely related with glucose utilization in patients with type 2 diabetes mellitus.

Influence of hypothalamically induced restlessness under fasted and fed conditions on plasma levels of glucose, free fatty acids and total cholesterol

AbstractInfluence of hypothalamically induced emotional behavior on plasma levels of epinephrine (E), norepinephrine (NE), glucose, cortisol, free fatty acids (FFA) and total cholesterol (T‐C) were examined in cats under both fasted and fed conditions. Restlessness was evoked intermittently for 6 h by electrical stimulation of the anteromedial hypothalamus (AMH). Blood was sampled immediately before, 1 h after and 6 h after the start of stimulation. Both E and glucose levels in the restlessness group increased markedly after 1 h and then tended to decrease after 6 h in fasted and fed states. In the restlessness group the NE level increased after 1 h and further increased after 6 h and cortisol level increased markedly, whether cats were fasted or fed. The FFA level in the fasted restlessness group showed no change while it increased in the fasted control group after 6 h. By contrast, the FFA level in the fed restlessness group significantly increased after 6 h while no change was observed in the fed control group. The T‐C level decreased only under the fasted condition in both restlessness and control groups. These results indicated that AMH‐induced restlessness elicited marked sympatho‐adrenal activation and hyperglycemia whether cats were fasted or fed while the behavior showed a different pattern in the response of plasma FFA between fasted and fed conditions. Copyright © 2001 John Wiley &amp; Sons, Ltd.

Physiological Modulation of Plasma Free Fatty Acid Concentrations by Diet: Metabolic implications in nondiabetic subjects

To determine the effect of varying the amount of carbohydrate and glycemic index (GI) of breakfast test meals on plasma free fatty acid (FFA) responses of nondiabetic subjects and to see whether the glycemic response at lunch was related to the plasma FFA response to breakfast. We studied eight subjects over a 6-h period on four separate occasions using a randomized Latin-square design. They received isocaloric breakfast test meals that were either high (84 g) or low (41 g) in carbohydrate and had either a high (approximately 100) or a low (approximately 70) GI, followed by a standard lunch 4 h later. The initial fall in plasma FFAs after breakfast was similar for all four test meals, but the extent of rebound differed significantly. The mean plasma FFA concentration just before the start of lunch (4 h) was highest after the low-GI, low-carbohydrate breakfast (418 +/- 42 mumol/l), followed by high-GI, low-carbohydrate (277 +/- 48 mumol/l), high-GI, high carbohydrate (227 +/- 32 mumol/l), and low-GI, high-carbohydrate (149 +/- 23 mumol/l) (P < 0.01). The concentration of plasma FFAs at 4 h was directly related to the total area under the glycemic response curve to lunch (r = 0.691, n = 32, P < 0.0001). In nondiabetic subjects, the type and amount of carbohydrate eaten at breakfast influences the plasma glucose, insulin, and FFA responses to breakfast and also affects the glucose, insulin, and FFA responses to a subsequent standard lunch. The glycemic responses after lunch were closely related to the plasma FFA concentration 4 h after breakfast, which we speculate is due to the inhibitory effect of FFAs on insulin action.

Body Composition and Cold Resistance of the Neonatal Pig from European (Large White) and Chinese (Meishan) Breeds

Body composition, plasma parameters and cold resistance were compared in neonatal pigs from Chinese (Meishan, Ms) and European (Large White, Lw) breeds. Newborn Ms pigs weighed less but had a higher (p less than 0.05) percentage of body dry matter and protein than the Lw pigs, whereas both breeds had similar levels of body fat and liver and muscle glycogen. Plasma concentrations of fructose and alpha-fetoprotein were lower (p less than 0.05) in the newborn Ms pigs. Cold resistance test performed in a 6-7 degrees C environment on the same piglets when aged 2 and 24 h, showed that in both breeds, cold resistance was closely dependent upon body weight and significantly improved (p less than 0.01) with age. Despite their 16% lower body weight, Ms piglets were, at both ages studied, as resistant to cold as the Lw ones. Breed had no effect on pretest concentration of plasma glucose and noradrenaline, but pretest concentrations of plasma free fatty acids (FFA) were higher (p less than 0.01) in the Ms than in Lw piglets and those of adrenaline were lower (p less than 0.01) in the Ms Lw piglets and those of adrenaline were lower (p less than 0.01) in the Ms piglets. Breed had no significant effect on the response of plasma glucose, FFA and catecholamines during exposure to cold. At both ages of exposure, plasma concentrations of glucose and catecholamines were significantly increased. Plasma concentrations of FFA were increased (p less than 0.01) at 2 h, but at 24 h a decrease (p less than 0.01) was observed during cold exposure. Colostrum from Ms sows had greater concentration of lipids than that from Lw sows. It is suggested that the similar resistance to cold of the Ms and Lw piglets despite the lower body weight of the former is due, in part, to a greater availability of FFA as an energy source.

Intravenous glycerol infusions: effect on free fatty acid metabolism

The plasma-free fatty acid response to intravenous glycerol infused at 250 and 500 mumol/min was determined in five normal volunteers in the postabsorptive state. There was a drop in free fatty acid concentration in all five subjects (one-way ANOVA, p less than 0.01) after the glycerol infusion with no change in insulin concentration compared to the post-absorptive state. These results suggest that intravenous glycerol infusions decrease free fatty acid concentrations in the post-absorptive state by an insulin-independent mechanism. When pharmacologic nonisotopic glycerol infusions are used to determined lipolytic rate, simultaneous measurement of free fatty acid concentrations should be interpreted with caution.

Effect of Warm-up on Plasma Free Fatty Acid Responses and Substrate Utilization during Submaximal Exercise

Abstract The purpose of this study was to examine the effect of preliminary walking on free fatty acid (FFA) responses and calculated substrate utilization during a 40-min treadmill run. Repeated 12-hour post-prandial measures were obtained on six endurance trained subjects (M [Vdot]RO2 max = 69.3 ml[mdot]kg-1[mdot]min-1) running at approximately 65% of their maximal aerobic power; preceded by rest in the without warm-up (WOW) trial or by a 20-min walk at approximately 27% of their maximal aerobic power in the with warm-up (WW) trial. Significantly different quadratic trends in FFA concentrations were found between trials. The WW trial displayed mean FFA concentrations above resting levels at sampling periods throughout the run. The WOW trial showed a fall in the mean FFA concentrations after the first 10 min of running, a return to approximately resting levels after 20 min, and elevated concentrations at 40 min. The percentage of energy derived from fat metabolism (calculated from steady state respirator...

Evidence for a longitudinal pathway in rat hypothalamus that controls FFA mobilization

In initial exploratory experiments, bilateral, symmetrical, relatively large electrolytic lesions were produced, injuring anterior, middle, and posterior hypothalamus but respecting the midlateral region. Only lesions in the preoptic-anterior hypothalamic region and in the posterior hypothalamus were effective in blocking free fatty acid (FFA) mobilization induced by intravenous 2-deoxyglucose. Lesions in the ventromedial hypothalamus were ineffective. In subsequent experiments, suppression of plasma FFA response to the drug was observed in rats with small, globular (0.5-1.0 mm diam), bilateral lesions either in the preoptic (PO) or in the lateral hypothalamic (LH) areas. Groups of animals were then prepared in which a unilateral lesion in the PO area was combined with a contralateral lesion in the LH area. Plasma FFA response to 2-deoxyglucose in these rats was also blocked but not in rats having only unilateral lesions. The hyperglycemic response to 2-deoxyglucose was not affected in any of the experimental groups. These data suggest that a longitudinal pathway connecting PO, LH, and posterior hypothalamic areas is involved in FFA mobilization from adipose tissue in rats.

The effect of chain length on glucose absorption and the related metabolic response

The relative absorption of saccharides of different chain length has been reexamined. Whether glucose is administered as a monosaccharide, a disaccharide (maltose), an intermediate polysaccharide mixture with a mean chain length of five glucose units (Caloreen), or a polysaccharide (starch), the rate of rise and fall in blood glucose concentration is similar in healthy subjects. In a maturity onset diabetic, peak blood glucose is similar whether monosaccharide or Caloreen is ingested. Plasma insulin and plasma free fatty acid responses to glucose saccharide ingestion do not appear to be affected by chain length. The dietary form in which starch is administered, rather than chain length, is probably important.

Evidence for centers in the central nervous system that selectively regulate fat mobilization in the rat

The blood sugar and plasma free fatty acid responses to administration of 2-deoxyglucose were determined in normal rats and in rats subjected to adrenodemedullation and/or hypothalamic deafferentation, as well as in rats with bilateral hypothalamic lesions. Adrenodemedullation of both intact and deafferentated rats reduced the 2-deoxyglucose-induced increase of blood sugar but did not affect the plasma free fatty acid response to 2-deoxyglucose in normal rats. The increases in blood sugar levels induced by the drug in intact rats were not significantly affected by deafferentation, but, in marked contrast, plasma free fatty acid mobilization after 2-deoxyglucose administration was completely suppressed in deafferentated rats, both in the presence and in the absence of the adrenal medulla. These results confirm previous observations indicating that the sympathetic nervous system and adrenalin release from the adrenal medulla participate in the production of hyperglycemia by 2-deoxyglucose. They provide, in addition, evidence for the existence, in the anterior hypothalamus or in limbic structures, of centers that can specifically influence mobilization of free fatty acids through a direct activation of the sympathetic fibers of adipose tissue without intervening in glucose homeostasis. The experiments in animals with bilateral hypothalamic lesions, although small in number, seem to support the above conclusions.

Human growth hormone secretion after double stimulation with arginine in normal and insulin-dependent diabetic women.

The standard intravenous arginine test was modified by infusing two equal doses of arginine eighty minutes apart. The serum growth hormone, blood glucose and plasma free fatty acid responses were studied in fifteen young juvenileonset diabetic women and in seven healthy women of comparable age and weight. The biphasic growth hormone response to the two arginine infusions observed in normals did not occur in the diabetics. In addition, the diabetics differed from the normals in several qualitative aspects of growth hormone secretion. A derangement in the diabetic is postulated with impaired sensitivity or defective mechanism of growth hormone secretion. Diabetics with chronically elevated blood glucose levels had a blunted growth hormone response to arginine. In five patients with diabetic retinopathy, growth hormone response was somewhat blunted, probably due to higher blood glucose levels, as compared with findings in five patients without this complication.

Lipid metabolism in Bilharzial cirrhosis

Skin-fold thickness as well as the fasting levels of blood lipids were studied in 66 patients with Bilharzial hepatic fibrosis (BHF) and 42 controls. The adipokinetic effect of glucose was studied on another group of 34 BHF patients and 20 controls. The lipolytic effect of epinephrine was also evaluated in 32 BHF patients and 17 controls. The plasma free fatty acids (FFA) in ascitic patients showed a statistically significant increase. Serum triglycerides, serum cholesterol, serum phosphatides, cholesterol phospholipid ratio ( C P ) and the β-/α-lipoprotein ratio were diminished to variable extents in BHF patients, a pattern opposite to that observed in ischaemic heart disease. There was no difference between the response of plasma FFA to intravenous glucose in patients and controls. Subcutaneous injection of epinephrine produced more elevation of plasma FFA in BHF patients than in controls. Skin-fold thickness was significantly decreased in patients with ascites. The possible mechanisms responsible for the above data, as well as their role in explaining the low incidence of thrombovascular lesions in BHF, together with the correlation between them, are discussed.

Offspring of two diabetic parents: differential serum insulin responses to intravenous glucose and tolbutamide.

Intravenous glucose tolerance tests and intravenous tolbutamide tests were performed in 14 non-obese male offspring of 2 diabetic parents and 25 non-obese male controls of comparable age. Blood glucose and plasma free fatty acid responses were similar in both groups during the 2 tests, as were the serum insulin levels during the tolbutamide test. The serum insulin response during the glucose tolerance test was significantly lower during the first 30 min in the prediabetics. There was a significant relationship between serum insulin and blood glucose during the glucose tolerance test in each group; comparisons revealed a significantly lower insulin-glucose relationship in the prediabetics. The magnitude of the insulin response during the tolbutamide test was correlated with that observed during the glucose tolerance test in the normals, but this correlation was no longer present in the prediabetics. These findings suggest that the beta cell of genetic prediabetics exhibits a defective glucose responsive mechanism for insulin secretion but that the tolbutamide responsive mechanism is normal.

Plasma free fatty acid response to exercise in obese humans

The effect of prolonged (4 hours) exercise on the concentration of plasma FFA was followed on 5 control subjects and on 4 obese patients. The response of plasma FFA was related to the energy expenditure measured as O 2 consumption. Plasma FFA increased during exercise to about the same value in both groups. When obese patients received a hypocaloric diet or entered a prolonged period (up to 26 days) of starvation, the resting value of FFA increased, but the final exercise value was the same as when they were on normocaloric diet. In the follow-up period, on close to normal caloric intake, the FFA returned to its baseline value, but the response to exercise was considerably depressed. While on hypocaloric diet or on starvation, the work RQ's were in the range of 0.71–0.74. Exercise failed to increase the urinary nitrogen output to any appreciable extent. It has been concluded (a) that our obese patients could readily mobilize FFA from their fat depots, in response to exercise; (b) that fat oxidation played a predominant role in their exercise metabolism; and (c) that even after prolonged starvation the participation of protein metabolism was negligible.

Plasma Free Fatty Acid Response to Prolonged Fasting in Simple Obesity of the Childhood

Plasma Free Fatty Acid Response to Prolonged Fasting in Simple Obesity of the Childhood

RELATIONSHIP BETWEEN RESISTANCE TO INSULIN AND BODY WEIGHT

SUMMARYThe relationship between increased body weight and resistance to insulin was studied in a group of 14 healthy men. The reduction in blood glucose and plasma free fatty acid (FFA) levels was measured during one‐hour infusions of insulin given in doses which would lead to physiological concentrations of insulin in the plasma.A relationship could not be demonstrated between the blood glucose response and body weight. However, the FFA concentrations fell to lower levels in the leaner than in the heavier subjects, so that a highly significant direct relationship was found between body weight and the post‐insulin plasma FFA concentration.The studies therefore show that, over a range of commonly encountered body weights, resistance to insulin develops with increasing fatness. The study also shows that the plasma FFA response to insulin is a more sensitive index of insulin resistance than the blood glucose response.

Plasma free fatty acid response to the administration of chorionic "growth hormone-prolactin".

In 4 children with documented hypopituitary dwarfism human chorionic “growth hormone-prolactin” (CGP) elicited a sharp, reproducible rise in the concentration of plasma free fatty acids within 4 hr when 100–400 mg was administered intramuscularly. The pattern of response simulated that of human growth hormone (HGH). The blood glucose concentration did not vary significantly from control studies. The apparent lipolytic effect of CGP in the absence of HGH provides supportive evidence of a growth hormone-like action for the placental hormone and of its important metabolic function during pregnancy.

Effects of diphenylhydantoin upon the plasma free fatty acid response induced by hormones.

Effects of diphenylhydantoin upon the plasma free fatty acid response induced by hormones.

LIPOLYTIC EFFECTS OF HUMAN GROWTH HORMONE IN RESISTANT OBESITY.

Plasma levels of free fatty acids (FFA) increased comparably in subjects of normal weight and in the extremely obese 4 hr after human growth hormone (HGH) was given intramuscularly in a body weight-related dose. Pretreatment of the very obese with HGH did not modify the subnormal response of plasma FFA to infused epinephrine.