scholarly journals STRUCTURE-FUNCTION RELATIONSHIPS IN THE ADIPOSE CELL

1970 ◽  
Vol 46 (2) ◽  
pp. 342-353 ◽  
Author(s):  
Samuel W. Cushman

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.

2007 ◽  
Vol 292 (3) ◽  
pp. E693-E701 ◽  
Author(s):  
André C. Carpentier ◽  
Frédérique Frisch ◽  
Pascal Brassard ◽  
François Lavoie ◽  
Annie Bourbonnais ◽  
...  

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.


2005 ◽  
Vol 288 (1) ◽  
pp. E80-E85 ◽  
Author(s):  
Bharathi Raju ◽  
Philip E. Cryer

To assess the mechanism, temporal patterns, and magnitudes of the metabolic responses to the ATP-dependent potassium channel agonist diazoxide, neuroendocrine and metabolic responses to intravenous diazoxide (saline, 1.0 and 2.0 mg/kg) and oral diazoxide (placebo, 4.0 and 6.0 mg/kg) were assessed in healthy young adults. Intravenous diazoxide produced rapid, but transient, decrements ( P = 0.0023) in plasma insulin (e.g., nadirs of 2.8 ± 0.5 and 1.8 ± 0.3 μU/ml compared with 7.0 ± 1.0 μU/ml after saline at 4.0–7.5 min) and C-peptide ( P = 0.0228) associated with dose-related increments in plasma glucose ( P = 0.0044) and serum nonesterified fatty acids ( P < 0.0001). After oral diazoxide, plasma insulin appeared to decline, as did C-peptide, again associated with dose-related increments in plasma glucose ( P < 0.0001) and serum nonesterified fatty acids ( P = 0.0141). Plasma glucagon, as well as cortisol and growth hormone, was not altered. Plasma epinephrine increased ( P = 0.0215) slightly only after intravenous diazoxide. There were dose-related increments in plasma norepinephrine ( P = 0.0038 and P = 0.0005, respectively), undoubtedly reflecting a compensatory sympathetic neural response to vasodilation produced by diazoxide, but these would not raise plasma glucose or serum nonesterified fatty acid levels. Thus selective suppression of insulin secretion, without stimulation of glucagon secretion, raised plasma glucose and serum nonesterified fatty acid concentrations. These findings define the temporal patterns and magnitudes of the metabolic responses to diazoxide and underscore the primacy of regulated insulin secretion in the physiological regulation of postabsorptive carbohydrate and lipid metabolism.


Author(s):  
Neil K. Huang ◽  
Mary L. Biggs ◽  
Nirupa R. Matthan ◽  
Luc Djoussé ◽  
W. T. Longstreth ◽  
...  

Background Significant associations between total nonesterified fatty acid (NEFA) concentrations and incident stroke have been reported in some prospective cohort studies. We evaluated the associations between incident stroke and serum concentrations of nonesterified saturated, monounsaturated, polyunsaturated, and trans fatty acids. Methods and Results CHS (Cardiovascular Health Study) participants (N=2028) who were free of stroke at baseline (1996–1997) and had an archived fasting serum sample were included in this study. A total of 35 NEFAs were quantified using gas chromatography. Cox proportional hazards regression models were used to evaluate associations of 5 subclasses (nonesterified saturated, monounsaturated, omega (n)‐6 polyunsaturated, n‐3 polyunsaturated, and trans fatty acids) of NEFAs and individual NEFAs with incident stroke. Sensitivity analysis was conducted by excluding cases with hemorrhagic stroke (n=45). A total of 338 cases of incident stroke occurred during the median 10.5‐year follow‐up period. Total n‐3 (hazard ratio [HR], 0.77 [95% CI, 0.61–0.97]) and n‐6 (HR, 1.32 [95% CI, 1.01–1.73]) subclasses of NEFA were negatively and positively associated with incident stroke, respectively. Among individual NEFAs, dihomo‐γ‐linolenic acid (20:3n‐6) was associated with higher risk (HR, 1.29 [95% CI, 1.02–1.63]), whereas cis ‐7‐hexadecenoic acid (16:1n‐9 c ) and arachidonic acid (20:4n‐6) were associated with a lower risk (HR, 0.67 [95% CI, 0.47–0.97]; HR, 0.81 [95% CI. 0.65–1.00], respectively) of incident stroke per standard deviation increment. After the exclusion of cases with hemorrhagic stroke, these associations did not remain significant. Conclusions A total of 2 NEFA subclasses and 3 individual NEFAs were associated with incident stroke. Of these, the NEFA n‐3 subclass and dihomo‐γ‐linolenic acid are diet derived and may be potential biomarkers for total stroke risk.


2020 ◽  
Vol 318 (3) ◽  
pp. E392-E404
Author(s):  
Rachel E. Walker ◽  
Jennifer L. Ford ◽  
Raymond C. Boston ◽  
Olga V. Savinova ◽  
William S. Harris ◽  
...  

In adipose, insulin functions to suppress intracellular lipolysis and secretion of nonesterified fatty acid (NEFA) into plasma. We applied glucose and NEFA minimal models (MM) following a frequently sampled intravenous glucose tolerance test (FSIVGTT) to assess glucose-specific and NEFA-specific insulin resistance. We used total NEFA and individual fatty acids in the NEFA MM, comparing the model parameters in metabolic syndrome (MetSyn) subjects ( n = 52) with optimally healthy controls (OptHC; n = 14). Results are reported as mean difference (95% confidence interval). Using the glucose MM, MetSyn subjects had lower [−73% (−82, −57)] sensitivity to insulin (Si) and higher [138% (44, 293)] acute insulin response to glucose (AIRg). Using the NEFA MM, MetSyn subjects had lower [−24% (−35, −13)] percent suppression, higher [32% (15, 52)] threshold glucose (gs), and a higher [81% (12, 192)] affinity constant altering NEFA secretion (ϕ). Comparing fatty acids, percent suppression was lower in myristic acid (MA) than in all other fatty acids, and the stearic acid (SA) response was so unique that it did not fit the NEFA MM. MA and SA percent of total were increased at 50 min after glucose injection, whereas oleic acid (OA) and palmitic acid (PA) were decreased ( P < 0.05). We conclude that the NEFA MM, as well as the response of individual NEFA fatty acids after a FSIVGTT, differ between OptHC and MetSyn subjects and that the NEFA MM parameters differ between individual fatty acids.


2007 ◽  
Vol 194 (2) ◽  
pp. 267-273 ◽  
Author(s):  
D C Ferguson ◽  
Z Caffall ◽  
M Hoenig

The obese cat is a model for the study of the progression toward type 2 diabetes. In this study, the impact of obesity on the hypothalamic–pituitary–thyroid axis was examined in 21 domestic shorthair cats before and after the development of obesity, which significantly increased body mass index (BMI), % body fat (BF), and girth (P<0.0001 for all). Serum total thyroxine (TT4), tri-iodothyronine, free T4 (FT4) by direct dialysis, nonesterified fatty acids (NEFA), and leptin were measured, and FT4 fraction (FFT4) was calculated. Serum thyrotropin (TSH) concentrations were measured in nine animals by validating a heterologous canine TSH assay with recombinant feline TSH as a standard. FT4, FFT4, NEFAs, and leptin were significantly higher in obese cats. FT4 had the strongest positive correlation with obesity indices BF, BMI, girth, NEFA, and leptin. Fatty acids oleate and palmitate were shown to inhibit T4 binding to pooled cat serum in vitro, suggesting the possibility that this mechanism was also relevant in vivo. Serum TT4 and TSH did not rise significantly. The implications for thyroid hormone (TH) action are not yet clear, but fatty acids have been proposed to inhibit the cellular uptake of TH and/or pituitary TH receptor binding, leading to TH resistance. Increased leptin may also alter sensitivity to negative feedback of TH. In conclusion, feline obesity is associated with a significant increase in FT4 within the normal range; future investigation into the cellular thyroid status will be necessary to establish cause and effect in this obesity model.


2015 ◽  
Vol 308 (5) ◽  
pp. G442-G449 ◽  
Author(s):  
Cordelia A. Running ◽  
Richard D. Mattes

Health concerns have led to recommendations to replace saturated fats with unsaturated fats. However, addition of unsaturated fatty acids may lead to changes in the way foods are perceived in the oral cavity. This study tested the taste sensitivity to and emulsion characteristics of oleic, linoleic, and α-linolenic acids. The hypothesis tested was that oral sensitivity to nonesterified fatty acids would increase with degree of unsaturation but that in vitro viscosities and particle sizes of these emulsions would not differ. Oral taste thresholds were obtained using the three-alternative, forced-choice, ascending method. Each participant was tested on each fat 7 times, for a total of 21 study visits, to account for learning effects. Viscosities were obtained for the blank solutions and all three emulsions. Results indicate lower oral thresholds to linoleic and α-linolenic than oleic acid. At higher shear rates, 5% oleic and linoleic acid were more viscous than other samples. More-dilute emulsions showed no significant differences in viscosity. Particle sizes of the emulsions increased very slightly with increasing unsaturation. Together, the emulsion characteristics and oral sensitivity data support a taste mechanism for nonesterified fatty acid detection.


1986 ◽  
Vol 55 (02) ◽  
pp. 250-258 ◽  
Author(s):  
K J Stevenson ◽  
Ann C Easton ◽  
A Curry ◽  
Jean M Thomson ◽  
L Poller

SummaryWide variations in procoagulant properties, lipid composition and ultrastructure of five commonly used APTT methods have been demonstrated. Performance of the methods with a range of coagulation abnormalities has been ranked. Most of the reagents obtained a high score with one or more defects, but a low score with others. A consistent good ranking throughout was only observed with one reagent.The number of significant correlations between the reagents’ procoagulant activities and lipid content confirms the view that the performance of an APTT method is largely dependent upon its lipid composition. Marked differences in concentration and distribution of phospholipids, fatty acids and neutral lipids were evident. The importance of the concentration of phosphatidyl serine in regulating the procoagulant activity of an APTT method has been demonstrated. Electron microscopy provides evidence of the contrasting composition of the reagents from the more discrete uniform liposomes present in the more reliable reagents, to more ill-defined components present in those reagents which performed less well. The study highlights the need for standardisation of the APTT.


1984 ◽  
Vol 224 (2) ◽  
pp. 651-659 ◽  
Author(s):  
N A Schroedl ◽  
C R Hartzell

Non-esterified fatty acids are used to a limited extent as an energy source in the newborn-mammalian heart. Therefore additional roles for palmitic and oleic acids during this early period of growth and development were investigated in the cultured neonatal-rat heart cell model system. Our results indicate significant differences in nonesterified-fatty-acid metabolism exist in this system in comparison with the adult rat or embryonic chick heart. Initial rates of depletion of palmitate and oleate from serum-free growth medium by heart cells obtained from 2-day-old rats and maintained in culture for 10 or 11 days were 111 +/- 2 and 115 +/- 3 pmol/min per mg of protein respectively. In serum-containing medium, the initial depletion rates were 103 +/- 3 and 122 +/- 4 pmol/min per mg of protein respectively, when endogenous serum nonesterified-fatty-acid concentrations were included in rate calculations. Less than 1% of the intracellularly incorporated fatty acids were found in aqueous products at any time. After 25 h, 15.5% of the initial palmitate was deposited intracellularly in the phosphatidylcholine lipid fraction, 4.2% in the triacylglycerol + fatty-acid-ester fraction and 3.1% in the sphingomyelin fraction. These results contradict the classical view, based on findings with the lipid-dependent adult heart, that exogenous nonesterified fatty acids are directed intracellularly primarily to pathways of oxidation or to storage as triacylglycerol. More importantly, it underscores the significance of exogenous non-esterified fatty acids in membrane biosynthesis of the developing mammalian heart. Included here is a new method for one-dimensional t.l.c. separation of metabolically important polar lipids.


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