On the suppression of plasma nonesterified fatty acids by insulin during enhanced intravascular lipolysis in humans

2005 ◽  
Vol 289 (5) ◽  
pp. E849-E856 ◽  
Author(s):  
André C. Carpentier ◽  
Frédérique Frisch ◽  
Denis Cyr ◽  
Philippe Généreux ◽  
Bruce W. Patterson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Nicotinic Acid ◽  
Insulin Level ◽  
Systemic Circulation ◽  
Nonesterified Fatty Acid ◽  
Plasma Nefa ◽  
Nonesterified Fatty Acids ◽  
Oxidation Rates ◽  
Healthy Humans ◽  
High Insulin

During the fasting state, insulin reduces nonesterified fatty acid (NEFA) appearance in the systemic circulation mostly by suppressing intracellular lipolysis in the adipose tissue. In the postprandial state, insulin may also control NEFA appearance through enhanced trapping into the adipose tissue of NEFA derived from intravascular triglyceride lipolysis. To determine the contribution of suppression of intracellular lipolysis in the modulation of plasma NEFA metabolism by insulin during enhanced intravascular triglyceride lipolysis, 10 healthy nonobese subjects underwent pancreatic clamps at fasting vs. high physiological insulin level with intravenous infusion of heparin plus Intralipid. Nicotinic acid was administered orally during the last 2 h of each 4-h clamp to inhibit intracellular lipolysis and assess insulin’s effect on plasma NEFA metabolism independently of its effect on intracellular lipolysis. Stable isotope tracers of palmitate, acetate, and glycerol were used to assess plasma NEFA metabolism and total triglyceride lipolysis in each participant. The glycerol appearance rate was similar during fasting vs. high insulin level, but plasma NEFA levels were significantly lowered by insulin. Nicotinic acid significantly blunted the insulin-mediated suppression of plasma palmitate appearance and oxidation rates by ∼60 and ∼70%, respectively. In contrast, nicotinic acid did not affect the marked stimulation of palmitate clearance by insulin. Thus most of the insulin-mediated reduction of plasma NEFA appearance and oxidation can be explained by suppression of intracellular lipolysis during enhanced intravascular triglyceride lipolysis in healthy humans. Our results also suggest that insulin may affect plasma NEFA clearance independently of the suppression of intracellular lipolysis.

Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans

2007 ◽  
Vol 292 (3) ◽  
pp. E693-E701 ◽  
Author(s):  
André C. Carpentier ◽  
Frédérique Frisch ◽  
Pascal Brassard ◽  
François Lavoie ◽  
Annie Bourbonnais ◽  
...  
Keyword(s):  
Insulin Level ◽  
Nonesterified Fatty Acid ◽  
Plasma Nefa ◽  
Experimental Conditions ◽  
Nonesterified Fatty Acids ◽  
Insulin Levels ◽  
Appearance Rate ◽  
Plasma Insulin Levels ◽  
Nefa Level ◽  
The Relationship

Insulin increases plasma nonesterified fatty acid (NEFA) clearance in humans, but whether this is independent of change in plasma NEFA appearance is currently unknown. Nine nondiabetic men (age: 28 ± 3 yr, body mass index: 27.2 ± 1.7 kg/m2) underwent euglycemic clamps to maintain low (LINS) vs. high (HINS) physiological insulin levels for 6 h. An intravenous infusion of heparin + Intralipid (HI) was performed during 4 of the 6 h of the clamps (in the last 4 h at LINS and in the first 4 h at HINS), whereas saline infusion (SAL) was administered in the remaining 2 h to modulate plasma NEFA levels independently of plasma insulin levels. Four experimental conditions were obtained in each individual: LINS with saline (LINS/SAL) and with HI infusion (LINS/HI) and HINS with saline (HINS/SAL) and with HI infusion (HINS/HI). Plasma palmitate appearance during HINS/SAL was lower than during the three other experimental conditions ( P < 0.05). In contrast, plasma linoleate appearance, as expected, was increased by HI independently of insulin level ( P < 0.02). Plasma palmitate clearance during HINS/SAL was higher than LINS/SAL and LINS/HI ( P < 0.008), and this increase was blunted during HINS/HI. We observed a linear decrease in plasma palmitate clearance with increasing plasma NEFA appearance independent of insulin levels. Plasma NEFA levels increased exponentially with increase in plasma NEFA appearance. We conclude that insulin stimulates plasma NEFA clearance by reducing the endogenous appearance rate of NEFA. The relationship between plasma NEFA level and appearance rate is nonlinear.

Effects of adipokine zinc-α2-glycoprotein on adipose tissue metabolism after dexamethasone treatment

2019 ◽  
Vol 44 (1) ◽  
pp. 83-89
Author(s):  
Yu Qiao ◽  
Guoqiang Fan ◽  
Jun Guo ◽  
Shixing Gao ◽  
Ruqian Zhao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Group Analysis ◽  
Adenosine Monophosphate ◽  
Experimental Models ◽  
Hormone Sensitive Lipase ◽  
Nonesterified Fatty Acid ◽  
Plasma Nefa ◽  
Lipid Mobilization ◽  
Protein Levels

Zinc-α2-glycoprotein (ZAG) has been demonstrated to play a role in stimulating lipid mobilization under normal conditions. However, further studies are required to determine whether ZAG overexpression can alleviate the reduction in plasma lipid levels under stress conditions. In the present study, we investigated the effects of ZAG on lipometabolism in white adipose tissue (WAT) after dexamethasone (DEX) stimulation using C57BL/6 male mice as the experimental models. Transcript and protein levels of genes associated with the β-adrenoreceptor (β-AR)/cyclic adenosine monophosphate/protein kinase a (PKA) pathway, lipid mobilization, and energy metabolism were determined by quantitative real-time polymerase chain reaction and Western blotting. Plasma levels of nonesterified fatty acid (NEFA) were measured using an automatic biochemical analyzer. Results indicated that plasma NEFA levels were decreased in the DEX group, but NEFA levels were rescued by ZAG overexpression. ZAG overexpression resulted in the upregulation of β3-AR and phosphorylated PKA protein relative to those of the DEX group. Analysis of lipometabolism showed that protein levels of phosphorylated hormone-sensitive lipase was reduced upon DEX treatment but were restored by ZAG overexpression. For energy metabolism, ZAG significantly upregulated the protein expression of carnitine palmitoyltransferase1a and cytochrome c oxidase subunit 1 relative to those of the DEX group. In conclusion, ZAG could alleviate DEX-induced decrease in plasma NEFA levels and this could be associated with the promoting lipid mobilization in WAT.

Do nonesterified fatty acids regulate skeletal muscle protein turnover in humans?

1993 ◽  
Vol 265 (3) ◽  
pp. E357-E361 ◽  
Author(s):  
M. Walker ◽  
E. Shmueli ◽  
S. E. Daley ◽  
B. G. Cooper ◽  
K. G. Alberti
Keyword(s):  
Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Serum Insulin ◽  
Whole Body ◽  
Nonesterified Fatty Acid ◽  
Elevated Plasma ◽  
Skeletal Muscle Protein ◽  
Plasma Nefa ◽  
Nonesterified Fatty Acids

We examined whether elevated plasma nonesterified fatty acid (NEFA) levels exert a direct effect on protein metabolism by measuring [2H5]phenylalanine skeletal muscle exchange and whole body turnover. [2H5]phenylalanine was infused (0.5 mg.kg-1 x h-1) for 300 min in seven healthy subjects on two occasions. Intralipid (10%; 30 ml/h) or 0.154 mol/l NaCl was infused in random order from 120 min. Measurements were taken during basal (90-120 min) and infusion (270-300 min) periods. Intralipid infusion increased plasma NEFA levels [1.31 +/- 0.13 vs. 0.49 +/- 0.05 (SE) mmol/l; P < 0.05] and forearm NEFA uptake [45 +/- 76 vs. -51 +/- 44 nmol . 100 ml forearm-1 x min-1; P < 0.05]. Serum insulin and blood ketone body levels were similar with the two treatments. Elevated plasma NEFA levels were associated with a comparable decrease in forearm phenylalanine uptake (11 +/- 2 vs. 17 +/- 2 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05) and release (20 +/- 2 vs. 26 +/- 3 nmol x 100 ml forearm-1 x min-1; lipid vs. control, P < 0.05). However, there were no significant changes in net forearm phenylalanine exchange and whole body phenylalanine turnover. Therefore, elevated plasma NEFA levels were associated with a comparable decrease in the rates of skeletal muscle protein synthesis and breakdown but did not appear to influence overall protein balance, as assessed using [2H5]phenylalanine.

scholarly journals Fat metabolism in formerly obese women

1998 ◽  
Vol 274 (1) ◽  
pp. E155-E161 ◽  
Author(s):  
Claudia Ranneries ◽  
Jens Bülow ◽  
Benjamin Buemann ◽  
Niels Juel Christensen ◽  
Joop Madsen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Exercise Bout ◽  
Fat Oxidation ◽  
Whole Body ◽  
Moderate Intensity ◽  
Obese Women ◽  
Glycerol Release ◽  
Nonesterified Fatty Acids ◽  
Oxidation Rates ◽  
Fat Mobilization

An impaired fat oxidation has been implicated to play a role in the etiology of obesity, but it is unclear to what extent impaired fat mobilization from adipose tissue or oxidation of fat is responsible. The present study aimed to examine fat mobilization from adipose tissue and whole body fat oxidation stimulated by exercise in seven formerly obese women (FO) and eight matched controls (C). Lipolysis in the periumbilical subcutaneous adipose tissue, whole body energy expenditure (EE), and substrate oxidation rates were measured before, during, and after a 60-min bicycle exercise bout of moderate intensity. Lipolysis was assessed by glycerol release using microdialysis and blood flow measurement by 133Xe clearance technique. The FO women had lower resting EE than C (3.77 ± 1.01 vs. 4.88 ± 0.74 kJ/min, P < 0.05) but responded similarly to exercise. Adipose tissue glycerol release was twice as high in FO than in C at rest (0.455 ± 0.299 vs. 0.206 ± 0.102 μmol ⋅ 100 g−1 ⋅ min−1, P < 0.05) but increased similarly in FO and C in response to exercise. Despite higher plasma nonesterified fatty acids (NEFA) in FO ( P < 0.001), fat oxidation rates during rest and recovery were lower in FO than in C (1.32 ± 0.84 vs. 3.70 ± 0.57 kJ/min, P < 0.02) and fat oxidation for a given plasma NEFA concentration was lower at rest ( P < 0.001) and during exercise ( P = 0.01) in the formerly obese group. In conclusion, fat mobilization both at rest and during exercise is intact in FO, whereas fat oxidation is subnormal despite higher circulation NEFA levels. The lower resting EE and the failure to use fat as fuel contribute to a positive fat balance and weight gain in FO subjects.

scholarly journals Muscle metabolome and adipose tissue mRNA expression of lipid metabolism-related genes in over-conditioned dairy cows differing in serum-metabotype

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hassan Sadri ◽  
Morteza Hosseini Ghaffari ◽  
Katharina Schuh ◽  
Christian Koch ◽  
Helga Sauerwein
Keyword(s):  
Adipose Tissue ◽  
Dairy Cows ◽  
Body Condition Score ◽  
Subcutaneous Fat ◽  
Oxidative Capacity ◽  
Mrna Abundance ◽  
Targeted Metabolomics ◽  
Healthy Humans ◽  
Condition Score ◽  
Metabolically Healthy

AbstractOver-conditioned dairy cows, classified by body condition score (BCS) and backfat thickness (BFT) are less able to metabolically adapt to the rapidly increasing milk yield after parturition. Based on serum metabolome and cluster analyses, high BCS cows (HBCS) could be classified into metabotypes that are more similar to normal (NBCS) cows, i.e., HBCS predicted normal (HBCS-PN) than the HBCS predicted high (HBCS-PH) cows—similar to the concept of obese but metabolically healthy humans. Our objective was to compare muscle metabolome and mRNA abundance of genes related to lipogenesis and lipolysis in adipose tissue between HBCS-PH (n = 13), HBCS-PN (n = 6), and NBCS-PN (n = 15). Tail-head subcutaneous fat was biopsied on d −49, 3, 21, and 84 relative to parturition. Potential differences in the oxidative capacity of skeletal muscle were assessed by targeted metabolomics in M. semitendinosus from d 21. Besides characteristic changes with time, differences in the mRNA abundance were limited to lipogenesis-related genes on d −49 (HBCS-PH > HBCS-PN). The HBCS-PH had more than two-fold higher muscle concentrations of short (C2, C4-OH, C6-OH) and long-chain acylcarnitines (C16, C18, and C18:1) than HBCS-PN, indicating a greater oxidative capacity for fatty acids (and utilization of ketones) in muscle of HBCS-PN than HBCS-PH cows.

scholarly journals Effects of Physiological Hypercortisolemia on the Regulation of Lipolysis in Subcutaneous Adipose Tissue1

1998 ◽  
Vol 83 (2) ◽  
pp. 626-631 ◽  
Author(s):  
Jaswinder S. Samra ◽  
Mo L. Clark ◽  
Sandy M. Humphreys ◽  
Ian A. MacDonald ◽  
Peter A. Bannister ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Sodium Succinate ◽  
Hormone Sensitive Lipase ◽  
Whole Body ◽  
Constant Infusion ◽  
Nonesterified Fatty Acid ◽  
Significant Difference ◽  
Hormone Sensitive ◽  
Subcutaneous Adipose

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused iv to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 ± 100 vs. 335± 25 nmol/L; P &lt; 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the sc adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of[ 1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P &lt; 0.01) and blood glycerol concentrations (P &lt; 0.05), with an increase in systemic glycerol appearance (P &lt; 0.05). However, in sc abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P &lt; 0.05) and reduced NEFA efflux (P &lt; 0.05). This reduction was attributable to decreased intracellular lipolysis (P &lt; 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P &lt; 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

Seasonal Variation in Plasma Nonesterified Fatty Acids of Lake Sturgeon (Acipenser fulvescens) in the Vicinity of Hydroelectric Facilities

1993 ◽  
Vol 50 (11) ◽  
pp. 2440-2447 ◽  
Author(s):  
R. S. McKinley ◽  
T. D. Singer ◽  
J. S. Ballantyne ◽  
G. Power
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lake Sturgeon ◽  
Acipenser Fulvescens ◽  
Total Plasma ◽  
Nefa Concentration ◽  
Plasma Nefa ◽  
Nonesterified Fatty Acids ◽  
Plasma Nefa Concentration ◽  
Fatty Acid Species

To establish the effects of hydroelectric generation on the health of lake sturgeon (Acipenser fulvescens), seasonal variations in plasma nonesterified fatty acids (NEFAs) upstream and downstream from hydroelectric stations were measured over a 2-yr period. Plasma NEFA profiles were also compared up- and downstream of the stations for differences in utilization of individual NEFA species as substrates for lipid oxidation. Significantly higher levels of total plasma NEFA were found in lake sturgeon upstream (2355 ± 395.9 nmol/mL) compared with those downstream (798 ± 133.5 nmol/mL) of the generating stations during the spring. The NEFA profiles for several key fatty acid species differed significantly among seasons up- and downstream of the facilities. In particular, during spring and summer, the levels of oleic acid (18:1n9) were highest upstream of the stations and levels of a polyunsaturated fatty acid, docosahexaenoic acid (22:6n3), were higher below rather than above the stations. The differences in plasma NEFA concentration may be attributed to altered nutritional status due to the varying flow regime located downstream of the hydroelectric stations.

scholarly journals STRUCTURE-FUNCTION RELATIONSHIPS IN THE ADIPOSE CELL

1970 ◽  
Vol 46 (2) ◽  
pp. 342-353 ◽  
Author(s):  
Samuel W. Cushman
Keyword(s):  
Electron Microscopy ◽  
Fatty Acids ◽  
Colloidal Gold ◽  
Intracellular Transport ◽  
Nonesterified Fatty Acid ◽  
Experimental Conditions ◽  
Nonesterified Fatty Acids ◽  
Adipose Cell ◽  
Cell Functions ◽  
The Relationship

Pinocytic activity in the adipose cell has been examined by measuring the uptake of colloidal gold. Pinocytic activity occurs in the isolated adipose cell under all experimental conditions; a portion of the vesicular elements of the cell can be identified by electron microscopy as pinocytic in origin. The isolated adipose cell appears to take up serum albumin by pinocytosis. Pinocytic activity in the isolated adipose cell is enhanced by epinephrine, but not by insulin. The relationship between pinocytosis and the metabolic activity of the adipose cell has been studied by measuring simultaneously the uptake of radioactive colloidal gold, the incorporation of 14C-counts from U-glucose-14C into CO2, total lipid, triglyceride glycerol and triglyceride fatty acids, and the release of nonesterified fatty acids in the absence of hormones and in the presence of insulin or epinephrine. Correlations between hormone-produced alterations in lipid metabolism and in pinocytic activity suggest that intracellular nonesterified fatty acid levels are a factor in the regulation of both the cell's pinocytic activity and its metabolism and that pinocytosis in the adipose cell functions in the extracellular-intracellular transport of nonesterified fatty acids.

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