Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity

1992 ◽  
Vol 263 (1) ◽  
pp. E79-E84 ◽  
Author(s):  
L. C. Groop ◽  
R. C. Bonadonna ◽  
D. C. Simonson ◽  
A. S. Petrides ◽  
M. Shank ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Lipid Oxidation ◽  
Fat Mass ◽  
Total Lipid ◽  
Plasma Insulin ◽  
Plasma Insulin Concentration ◽  
Basal Rate ◽  
Plasma Ffa ◽  
Obese Subjects

The dose-response relationship between the plasma insulin concentration and oxidative and nonoxidative pathways of free fatty acid (FFA) metabolism was examined in 11 obese and 7 lean subjects using a stepwise insulin clamp technique in combination with indirect calorimetry and infusion of [1-14C]palmitate. The fasting plasma FFA concentration was elevated in obese subjects (793 +/- 43 vs. 642 +/- 39 mumol/l; P less than 0.01) and was associated with an increased basal rate of plasma FFA turnover, FFA oxidation, and nonoxidative FFA disposal, i.e., reesterification (all P less than 0.01). Suppression of plasma FFA turnover by physiological increments in plasma insulin was impaired in obese compared with lean subjects. However, plasma FFA turnover expressed per kilogram fat mass was normally suppressed by insulin in obese subjects. Although insulin suppressed plasma FFA oxidation to the same extent in lean and obese subjects, inhibition of total lipid oxidation by insulin was impaired in the obese group. Obese subjects had an enhanced basal rate of nonoxidative FFA disposal, which was suppressed less by physiological increments in plasma insulin compared with lean controls. Therefore, we conclude that 1) lipolysis in uncomplicated obesity is normally sensitive to insulin; the enhanced FFA flux is simply a consequence of the increased fat mass. 2) Nonoxidative FFA disposal expressed per lean body mass is enhanced in obese subjects and correlates with the increase in plasma FFA concentration and fat mass. 3) Enhanced oxidation of intracellular lipids contributes to the enhanced rate of total lipid oxidation in obese subjects.

Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans

1990 ◽  
Vol 259 (5) ◽  
pp. E736-E750 ◽  
Author(s):  
R. C. Bonadonna ◽  
L. C. Groop ◽  
K. Zych ◽  
M. Shank ◽  
R. A. DeFronzo
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Lipid Oxidation ◽  
Plasma Insulin ◽  
Plasma Free Fatty Acid ◽  
Whole Body ◽  
Glucose Disposal ◽  
Body Lipid ◽  
Plasma Ffa ◽  
Dose Dependent

Methodology for measuring plasma free fatty acid (FFA) turnover/oxidation with [1–14C]palmitate was tested in normal subjects. In study 1, two different approaches (720-min tracer infusion without prime vs. 150-min infusion with NaH14CO3 prime) to achieve steady-state conditions of 14CO2 yielded equivalent rates of plasma FFA turnover/oxidation. In study 2, during staircase NaH14CO3 infusion, calculated rates of 14CO2 appearance agreed closely with NaH14CO3 infusion rates. In study 3, 300-min euglycemic insulin clamp documented that full biological effect of insulin on plasma FFA turnover/oxidation was established within 60–120 min. In study 4, plasma insulin concentration was raised to 14 +/- 2, 23 +/- 2, 38 +/- 2, 72 +/- 5, and 215 +/- 10 microU/ml. A dose-dependent insulin suppression of plasma FFA turnover/oxidation was observed. Plasma FFA concentration correlated positively with plasma FFA turnover/oxidation in basal and insulinized states. Total lipid oxidation (indirect calorimetry) was significantly higher than plasma FFA oxidation in the basal state, suggesting that intracellular lipid stores contributed to whole body lipid oxidation. Hepatic glucose production and total glucose disposal showed the expected dose-dependent suppression and stimulation, respectively, by insulin. In conclusion, insulin regulation of plasma FFA turnover/oxidation is maximally manifest at low physiological plasma insulin concentrations, and in the basal state a significant contribution to whole body lipid oxidation originates from lipid pool(s) that are different from plasma FFA.

Free fatty acid and glucose metabolism in human aging: evidence for operation of the Randle cycle

1994 ◽  
Vol 266 (3) ◽  
pp. E501-E509 ◽  
Author(s):  
R. C. Bonadonna ◽  
L. C. Groop ◽  
D. C. Simonson ◽  
R. A. DeFronzo
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Metabolism ◽  
Lipid Oxidation ◽  
Lean Body Mass ◽  
Body Mass ◽  
Total Lipid ◽  
The Elderly ◽  
Glucose Turnover ◽  
Plasma Ffa

We assessed insulin effects on plasma free fatty acid (FFA) and glucose metabolism in seven elderly (71 +/- 2 yr) and in seven younger (21 +/- 1 yr) subjects matched for body weight and body mass index but not for percent body fat (32.4 +/- 3.8% in elderly vs. 20.4 +/- 3.5% in young, P < 0.05), by performing sequential euglycemic clamps at five insulin doses (0.6, 1.5, 3, 6, and 15 pmol.min-1.kg-1) in combination with indirect calorimetry and [1-14C]palmitate plus [3-3H]glucose infusion. At baseline, plasma FFA concentration, turnover infusion. At baseline, plasma FFA concentration, turnover and oxidation, and total lipid oxidation were all increased in the elderly (897 +/- 107 vs. 412 +/- 50 mumol/l and 11.2 +/- 1.4 vs. 5.14 +/- 0.86, 3.45 +/- 0.65 vs. 1.37 +/- 0.25, and 4.63 +/- 0.72 vs. 3.01 +/- 0.33 mumol.min-1.kg-1 lean body mass, P < 0.05 for all comparisons), whereas glucose turnover was similar as a result of decreased glucose oxidation (8.2 +/- 1.4 vs. 13 +/- 1.9 mumol.min-1.kg-1 lean body mass, P < 0.05) and increased glucose storage (6.6 +/- 1.4 vs. 1.7 +/- 1.3 mmol.min-1.kg-1 lean body mass, P < 0.05). At all insulin infusions, plasma FFA concentration, turnover and oxidation, and total lipid oxidation were higher in the elderly than in the younger group (P < 0.05). However, if normalized per fat mass, all FFA and lipid metabolic fluxes, both in the postabsorptive state and during hyperinsulinemia, were comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Metabolic Effects of Catecholamines in Sheep

1970 ◽  
Vol 23 (4) ◽  
pp. 903 ◽  
Author(s):  
JM Bassett
Keyword(s):  
Body Weight ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Intravenous Injection ◽  
Intravenous Infusion ◽  
Plasma Insulin ◽  
Metabolic Effects ◽  
Plasma Insulin Concentration ◽  
Adrenaline Infusion ◽  
Adrenaline Injection

Intravenous infusion of 1� 5 mg adrenaline over 30 min into adult Merino wethers (50 kg body weight), increased glucose, lactate, and free fatty acid (FFA) concentrations in plasma much more than did a single rapid intravenous injection of the same amount. There was no increase in plasma insulin concentration during adrenaline infusion or after adrenaline injection.

Increased insulin suppression of plasma free fatty acid concentration in exercise-trained rats

1993 ◽  
Vol 74 (1) ◽  
pp. 293-296 ◽  
Author(s):  
J. M. Lavoie ◽  
J. Bongbele ◽  
S. Cardin ◽  
M. Belisle ◽  
J. Terrettaz ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Exercise Training ◽  
Plasma Insulin ◽  
Plasma Free Fatty Acid ◽  
Mean Value ◽  
Free Fatty Acid Concentration ◽  
Mean Diameter ◽  
Plasma Ffa ◽  
Fat Depot

The effect of exercise training on the insulin suppression of plasma free fatty acid (FFA) concentrations was studied in unanesthetized rats with the hyperinsulinemic-euglycemic clamp technique. Seven rats trained (TR) for 3 h/day by continuous swimming during 8 wk were compared with 6 untrained (UT) body weight-matched rats. Both TR and UT rats were submitted to an exercise swimming session 18 h before the clamp. A smaller mean diameter of adipocytes sampled from the epididymal fat depot was measured in TR animals. The total quantity of glucose infused to maintain euglycemia was 2.2 times higher in TR than in UT animals. No significant differences in plasma insulin concentrations were found between the two groups throughout the experiment. Insulin infusions resulted in a 60% decrease of plasma FFA in TR rats (mean value: from 0.46 to 0.18 mM) compared with 27% in UT animals (mean value: from 0.45 to 0.33 mM). The data indicate a greater ability of insulin to suppress plasma FFA levels with exercise training, which suggests an increased antilipolytic action of insulin in adipocytes under this condition.

scholarly journals 146 Nutritional Advances in Fetal and neonatal development: effect of fatty acid supplementation

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 121-122
Author(s):  
Alejandro E Relling
Keyword(s):  
Small Intestine ◽  
Fatty Acid ◽  
Plasma Insulin ◽  
Linear Increase ◽  
Late Gestation ◽  
Insulin Concentration ◽  
Plasma Insulin Concentration ◽  
Pufa Supplementation ◽  
Epa And Dha ◽  
Offspring Growth

Abstract Data from a series of experiments demonstrates that maternal supply of polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), during late gestation affects offspring growth. The increase in growth is independent on the fatty acid supplemented during the growing or finishing phase of the offspring; but it is sex dependent. Dam PUFA supplementation increases wether growth. Supplementation with EPA and DHA to pregnant ewes and to their offspring after weaning showed a treatment interaction in mRNA concentration of hypothalamic neuropeptides associated with dry matter intake (DMI) regulation. A dose increased in EPA and DHA in pregnant ewe diets shows a linear increase in growth, but a quadratic change in DMI or feed efficiency; growth was associated with a linear increase in plasma glucose concentration and a linear decrease in plasma ghrelin concentration. In lambs born from ewes supplemented with different sources of FA during a glucose tolerance test; males’ plasma insulin concentration increased as FA unsaturation degree increased in the dam diet, the opposite happened with females’ plasma insulin concentration. Recent data from our lab showed that the supplementation with EPA and DHA during the last third of gestation to pregnant ewes increased liver and small intestine global DNA methylation and small intestine transporters for amino acids in the fetus. Despite EPA and DHA during late gestation increase growth in the offspring; when EPA and DHA were supplemented in early gestation, offspring growth was lesser that lambs born from ewes supplemented a saturated and monounsaturated lipid. The reason for the difference in results it is not clear. However, more studies focusing in some aspect of the biology will help to understand what specific fatty acid needs to be supplemented at different stages of gestation to improve offspring growth.

The Effects of Cold and Prostaglandin E1 on Lipid Mobilization in the Chicken

1971 ◽  
Vol 49 (5) ◽  
pp. 394-398 ◽  
Author(s):  
W. D. Wagner ◽  
R. A. Peterson ◽  
R. J. Cenedella
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Cold Exposure ◽  
Prostaglandin E1 ◽  
Plasma Free Fatty Acid ◽  
Prostaglandin E ◽  
Elevated Plasma ◽  
Lower Plasma ◽  
Lipid Mobilization ◽  
Plasma Ffa

Plasma free fatty acid (FFA) levels and the effects of prostaglandin E1 (PGE1) were studied in cold-acclimated and cold-exposed chickens and compared to controls. Chickens cold-acclimated at 4–7 or 8–11 °C for 4 weeks had significantly elevated plasma FFA when compared to the controls at 19–21 °C. Although PGE1 had no effect on the basal level of FFA of controls, a significantly lower plasma FFA was seen after injection of either 10 or 30 μg PGE1/kg in cold-acclimated chickens. Chickens cold-exposed to 2–3 °C for 4 h demonstrated significant elevations of plasma FFA when compared to controls. Only 30 μg PGE1/kg significantly depressed the plasma FFA in the cold-exposed birds. No inhibition of basal FFA release was seen in control animals. From these experiments, it is concluded that chickens mobilize FFA extensively under cold-exposure and that this stimulated lipolysis is inhibited by PGE1.

Influence of Free Fatty Acid Concentrations and Weight Loss on Adipose Tissue Direct Free Fatty Acid Storage Rates

2021 ◽  
Author(s):  
Qingyi Jia ◽  
B Gisella Carranza Leon ◽  
Michael D Jensen
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Subcutaneous Fat ◽  
Premenopausal Women ◽  
Tissue Level ◽  
Research Unit ◽  
Lower Body ◽  
Plasma Ffa

Abstract Context The factors that determine the recycling of free fatty acids (FFA) back into different adipose tissue depots via the direct storage pathway are not completely understood. Objective To assess the interactions between adipocyte factors and plasma FFA concentrations that determine regional FFA storage rates. Design We measured direct adipose tissue FFA storage rates before and after weight loss under high FFA (intravenous somatostatin and epinephrine) and low (intravenous insulin and glucose) FFA concentrations. Setting Mayo Clinic Clinical Research Unit. Patients Sixteen premenopausal women, BMI 30 - 37 kg/m 2. Intervention Comprehensive lifestyle weight loss program. Main Outcome Measure Direct FFA storage rates in upper and lower body subcutaneous fat. Results Over the entire range of FFA and under isolated conditions of elevated FFA concentrations the storage rates of FFA into upper and lower body subcutaneous fat per unit lipid were associated with concentrations, not adipocyte fatty acid storage factors. Under low FFA conditions, direct FFA storage rates were related to adipocyte CD36 content, not tissue level content of fatty acid storage factors. Weight loss did not change these relationships. Conclusions The regulation of direct FFA storage under low FFA concentration conditions appears to be at the level of the cell/adipocyte content of CD36, whereas under high FFA concentration conditions direct FFA storage at the tissue level is predicted by plasma FFA concentrations, independent of adipocyte size or fatty acid storage factors. These observations offer novel insights into how adipose tissue regulates direct FFA storage in humans.

Impaired plasma FFA oxidation imposed by extreme CHO deficiency in contracting rat skeletal muscle

1994 ◽  
Vol 77 (2) ◽  
pp. 517-525 ◽  
Author(s):  
L. P. Turcotte ◽  
P. J. Hespel ◽  
T. E. Graham ◽  
E. A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Uptake ◽  
Swimming Exercise ◽  
Rat Skeletal Muscle ◽  
Palmitate Oxidation ◽  
Plasma Ffa ◽  
Ffa Metabolism ◽  
Palmitate Uptake

The extent to which carbohydrate (CHO) availability affects free fatty acid (FFA) metabolism in contracting skeletal muscle is not well characterized. To study this question, rats were depleted of glycogen by swimming exercise and lard feeding 24 h before perfusion of their isolated hindquarters. After 20 min of preperfusion with a medium containing no glucose, palmitate (600 or 2,000 microM), and [1–14C]palmitate, flow was restricted to one hindlimb, which was electrically stimulated for 2 min to further deplete muscles of glycogen. After 2 min of recovery, glucose was added to the perfusate at final concentrations of 0, 6, or 20 mM, and after another 3 min muscles were stimulated for 30 min. At 6 and 2,000 microM palmitate, glucose uptake after 30 min of stimulation averaged 23.5 +/- 9.3 and 45.9 +/- 10.6 mumol.g-1.h-1 with 6 and 20 mM glucose, respectively. At 6 and 2,000 microM palmitate, palmitate uptake was lower (30–37%, P < 0.05) with 0 than with 6 or 20 mM glucose. At 600 microM palmitate, percent palmitate oxidation was higher (27%, P < 0.05) with 0 than with 6 or 20 mM glucose, resulting in similar total palmitate oxidation with the three glucose concentrations (0.28 +/- 0.01 mumol.g-1.h-1). At 2,000 microM palmitate, percent palmitate oxidation was not significantly different among glucose concentrations, resulting in a significantly lower rate of palmitate oxidation with 0 (0.62 +/- 0.18 mumol.g-1.h-1) than with 6 or 20 mM glucose (0.77 +/- 0.25 and 0.78 +/- 0.20 mumol.g-1.h-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and reesterification

2006 ◽  
Vol 263 (6) ◽  
pp. E1063-E1069 ◽  
Author(s):  
P. J. Campbell ◽  
M. G. Carlson ◽  
J. O. Hill ◽  
N. Nurjhan
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Acid Metabolism ◽  
Insulin Dose ◽  
Healthy Humans ◽  
Constant Rate ◽  
Free Fatty Acid Metabolism ◽  
Plasma Ffa ◽  
Maximal Suppression

The regulation of lipolysis, free fatty acid appearance into plasma (FFA R(a)), an FFA reesterification and oxidation were examined in seven healthy humans infused intravenously with insulin at rates of 4, 8, 25, and 400 mU.m-2.min-1. Glycerol and FFA R(a) were determined by isotope dilution methods, and FFA oxidation was calculated by indirect calorimetry or by measurement of expired 14CO2 from infused [1-14C]palmitate. These measurements were used to calculate total FFA reesterification, primary FFA reesterification occurring within the adipocyte, and secondary reesterification of circulating FFA molecules. Lipolysis, FFA R(a), and secondary FFA reesterification were exquisitely insulin sensitive [the insulin concentrations that produced half-maximal suppression (EC50), 106 +/- 26, 91 +/- 20 vs. 80 +/- 16 pM, P = not significant] in contrast to insulin suppression of FFA oxidation (EC50, 324 +/- 60, all P < 0.01). The absolute rate of primary FFA reesterification was not affected by the increase in insulin concentration, but the proportion of FFA molecules undergoing primary reesterification doubled over the physiological portion of the insulin dose-response curve (from 0.23 +/- 0.06 to 0.44 +/- 0.07, P < 0.05). This served to magnify insulin suppression of FFA R(a) twofold. In conclusion, insulin regulates FFA R(a) by inhibition of lipolysis while maintaining a constant rate of primary FFA reesterification.

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