scholarly journals Selective mobilization of fatty acids from white fat cells: evidence for a relationship to the polarity of triacylglycerols

1997 ◽  
Vol 322 (2) ◽  
pp. 483-489 ◽  
Author(s):  
Thierry RACLOT

Fatty acids are selectively released from white fat cells in accordance with well-defined rules relating their molecular structure and their mobilization rate, emphasizing the possible role of their physicochemical properties. Lipolysis is widely reported to work for conditions where only small amounts of substrate are available. We hypothesize that the preferential hydrolysis of a substrate fraction enriched in the most polar triacylglycerols (TAGs) reflects the pattern of selective fatty acid mobilization. Rat adipose tissue was first manipulated by dietary means to obtain a wide spectrum of fatty acids. Fat cell TAGs were separated into eight fractions according to polarity by liquid–liquid partition chromatography and their fatty acid proportions and compositions were determined by GLC. In the most polar TAG fractions, the relative enrichment of fatty acids (percentage in a TAG fraction divided by percentage in total TAGs) increased with the number of double bonds for a given chain length, whereas it decreased with increasing chain length for a given degree of unsaturation. The relative enrichment of highly mobilized fatty acids (16–20 carbon atoms and four or five double bonds) was very high (more than 2.5) in the most polar TAG fractions, whereas that of weakly mobilized fatty acids (20–24 carbon atoms and no or one double bond) was very low (less than 0.5). The relative enrichment of moderately mobilized fatty acids (comprising all the others) was close to unity. Our study shows that the relative enrichment of fatty acids in the most polar adipose tissue TAGs is consistent with their relative mobilization rates. This supports our hypothesis and raises the possibility that the molecular species of TAGs might be one of the regulating factors.

1997 ◽  
Vol 324 (3) ◽  
pp. 911-915 ◽  
Author(s):  
Thierry RACLOT ◽  
Dominique LANGIN ◽  
Max LAFONTAN ◽  
René GROSCOLAS

The objective of the present study was to investigate the mobilization of individual fatty acids from human white fat cells. Mammary adipose tissue from eight healthy non-obese women in their normal dietary state was collected, and isolated adipocytes were incubated with lipolytic agents. The mobilization of 34 individual fatty acids was measured by comparing the composition of non-esterified fatty acids (NEFA) with that of the triacylglycerols (TAG) from which they originated through lipolysis. Compared with TAG, NEFA were enriched in some polyunsaturated fatty acids with 18–20 carbon atoms. Conversely, the percentage of very-long-chain (20–22 carbon atoms) saturated and monounsaturated fatty acids was approx. 2 times lower in NEFA than in TAG. The relative mobilization (% in NEFA/% in TAG) of the most readily mobilized fatty acid (C20:5,n-3; 2.25) was more than 6-fold higher than that of the least readily mobilized (C22:1,n-11; 0.37). Relationships were found between the molecular structure of fatty acids and their mobilization rate. For a given chain length, the relative mobilization rate increased with increasing unsaturation, whereas for a given unsaturation, it decreased with increasing chain length. The relative mobilization rate for essential fatty acids decreased in the following order: C20:5,n-3 > C20:4,n-6 > C18:3,n-3 > C18:2,n-6 > C22:6,n-3. Interestingly, C20:5,n-3 and C20:4,n-6, which are respectively precursors of the 3- and 2-series of prostaglandins, were preferentially mobilized. It is concluded that fatty acids are selectively mobilized from human fat cells according to molecular structure, in full agreement with animal studies. By modulating the qualitative fatty acid supply to organs and by remodelling the fatty acid composition of adipose tissue, this selectivity would be relevant for consideration in physiology, health and epidemiology.


1995 ◽  
Vol 269 (5) ◽  
pp. R1060-R1067 ◽  
Author(s):  
T. Raclot ◽  
E. Mioskowski ◽  
A. C. Bach ◽  
R. Groscolas

This study extends our earlier work (T. Raclot and R. Groscolas. J. Lipid Res. 34: 1515-1526, 1993), which showed that, under norepinephrine-stimulated lipolysis, fatty acids of rat retroperitoneal fat cells are selectively mobilized. The present study examines whether this selective mobilization of fatty acids 1) is based on their proportions in adipose tissue, 2) is a metabolic feature common to all adipose tissues, and/or 3) depends on the lipolysis-stimulating agent. Rat fat cells with two markedly different fatty acid compositions were isolated from four white adipose tissues and treated with three lipolytic agents. Fatty acid composition of in vitro released free fatty acids was compared with that of fat cell triacylglycerols, the ratio of percent in free fatty acid to percent in triacylglycerol being defined as the relative mobilization rate (RMR). The RMR of individual fatty acids was related to their molecular structure. It increased exponentially with unsaturation for a given chain length and decreased with increasing chain length for a given unsaturation. The selectivity of fatty acid mobilization was similar regardless of the fatty acid composition of adipose tissue, the tissue location, and the lipolytic agent used. Under conditions of stimulated lipolysis, the selectivity of fatty acid mobilization is therefore a general metabolic feature of adipose tissue. Fatty acids with 16-20 carbon atoms and 4 or 5 double bonds had the highest RMR (from 1.4 to > 5), whereas fatty acids with 20-22 carbon atoms and 0 or 1 double bond had the lowest RMR (from 0.3 to 0.7). For the other fatty acids, RMR was close to unity.(ABSTRACT TRUNCATED AT 250 WORDS)


1995 ◽  
Vol 311 (3) ◽  
pp. 911-916 ◽  
Author(s):  
T Raclot ◽  
C Leray ◽  
A C Bach ◽  
R Groscolas

Fatty acids have been shown to be selectively mobilized from rat white fat-cells, whatever the dietary manipulations. For convenience, fatty acids have been classified as being highly, weakly and moderately mobilizable. The aim of this study was to examine whether the selective mobilization of fatty acids can be explained, even partly, by their positional distribution in adipose-tissue triacylglycerols (TAG) via the known specificity of hormone-sensitive lipase for the sn-1 and sn-3 positions. Adipose tissue was dietarily manipulated in order to obtain a wide spectrum of fatty acids, including large amounts of either very-long-chain polyunsaturated fatty acids (VLC-PUFA) or very-long-chain monounsaturated fatty acids (VLC-MUFA). The determination of fatty acid distribution in adipose tissue TAG was based on random formation of 1,2-diacyl-rac-glycerols by Grignard degradation, followed by synthesis of phosphatidic acids and hydrolysis in the sn-2 position by phospholipase A2. Regardless of the fatty acid composition and location of fat depots, highly (e.g. 18:4n-3 and some of the VLC-PUFA) and weakly (e.g. VLC-MUFA) mobilizable fatty acids were located mainly in the outer (sn-1 and sn-3) positions of the glycerol moiety (79.5% and 92.5% on average, respectively). Other fatty acids, which are rather moderately mobilizable, were more randomly distributed. We conclude that the selective mobilization of white-fat-cell fatty acids is not based on their positional distribution in TAG.


1970 ◽  
Vol 117 (5) ◽  
pp. 861-877 ◽  
Author(s):  
B. R. Martin ◽  
R. M. Denton

1. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25°C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD–isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP–malate dehydrogenase (11.0), ATP–citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP–isocitrate dehydrogenase (3.7), NAD–malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109μg/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3–6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP–citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.


1975 ◽  
Vol 150 (3) ◽  
pp. 441-451 ◽  
Author(s):  
S R Sooranna ◽  
E D Saggerson

1. When rat isolated fat-cells were incubated with fructose and palmitate, insulin significantly stimulated glyceride synthesis as measured by either [14C]fructose incorporation into the glycerol moiety or of [3H]palmitate incorporation into the acyl moiety of tissue glycerides. Under certain conditions the effect of insulin on glyceride synthesis was greater than the effect of insulin on fructose uptake. 2. In the presence of palmitate, insulin slightly stimulated (a) [14C]pyruvate incorporation into glyceride glycerol of fat-cells and (b) 3H2O incorporation into glyceride glycerol of incubated fat-pads. 3. At low extracellular total concentrations of fatty acids (in the presence of albumin), insulin stimulated [14C]fructose, [14C]pyruvate and 3H2O incorporation into fat-cell fatty acids. Increasing the extracellular fatty acid concentration greatly inhibited fatty acid synthesis from these precursors and also greatly decreased the extent of apparent stimulation of fatty acid synthesis by insulin. 4. These results are discussed in relation to the suggestion [A.P. Halestrap & R.M Denton (1974) Biochem. J. 142, 365-377] that the tissue may contain a specific acyl-binding protein which is subject to regulation. It is suggested that an insulin-sensitive enzyme component of the glyceride-synthesis process may play such a role.


1999 ◽  
Vol 58 (3) ◽  
pp. 633-646 ◽  
Author(s):  
Thierry Raclot ◽  
Hugues Oudart

Triacylglycerols represent the main form of storage for a wide spectrum of fatty acids. Their utilization first involves mobilization from adipose tissue through lipolysis. The release of individual fatty acids from adipose tissue is selective in vitro and in vivo in animal studies and also in human subjects. Generally, fatty acids are more readily mobilized from fat cells when they are short-chain and unsaturated. This selectivity could affect the storage of individual fatty acids in adipose tissue, and their subsequent supply to tissues. The nature of the dietary fats could affect lipid homeostasis and body fat deposition. Dietary fish oil influences adipose tissue development in a site-specific manner as a function of diet and feeding period. A diet high in n-3 polyunsaturated fatty acids (PUFA) results in a preferential partitioning of ingested energy towards oxidation at the expense of storage. Fatty acids are important mediators of gene expression in the liver. Indeed, genes encoding both glycolytic and lipogenic enzymes and key metabolic enzymes involved in fatty acid oxidation are regulated by dietary PUFA. White adipose tissue could also be a target for PUFA control of gene expression. The treatment of pre-adipose cells by fatty acids induces the expression of numerous genes that encode proteins involved in fatty acid metabolism. The mechanisms of PUFA-mediated repression of gene expression in adipocytes seem to be different, at least partly, from those described in liver. Tissue-specific and site-specific factors are possibly involved in the specific effect of PUFA on gene expression, although other mechanisms cannot be excluded.


1968 ◽  
Vol 46 (9) ◽  
pp. 1039-1045 ◽  
Author(s):  
Anna M. Daniel ◽  
David Rubinstein

Some characteristics of enzymes in homogenates of rat adipose tissue concerned with esterification of fatty acids have been investigated. Acyl-CoA thiokinase is the most active of the enzymes studied, with optimal concentrations of palmitate and ATP being 2 mM and 25 mM respectively. The thiokinase has a pH optimum between 8 and 10 and reacts with fatty acids ranging in chain length from C4 to C22, with the greatest activity towards palmitate. About 50% of the activity is found in the 100 000 × g supernatant. Acyl-CoA : α-glycerolphosphate acyltransferase and acyl-CoA deacylase have pH optima between 7 and 8. Albumin at a concentration of 1% activates the former, while the latter is inhibited by concentrations of albumin greater than 0.5%. Deacylase activity is found almost entirely in the 100 000 × g supernatant. Both the acyl-CoA : α-glycerolphosphate acyltransferase and the acyl-CoA : diglyceride acyltransferase lose much of their activity upon fractionation. The pH optimum of the acyl-CoA : diglyceride acyltransferase ranges from pH 7 to 9, while that of the phosphatidc acid phosphatase is 6. The latter enzyme is distributed equally between particulate and soluble portions of the homogenate. When these enzymes are assayed in homogenates from fed and fasted animals, a significant alteration is found only in the level of acyl-CoA deacylase, which is decreased. The properties of these enzymes can be related to the extent and type of esterification in homogenates from fed and fasted animals.


1985 ◽  
Vol 54 (03) ◽  
pp. 563-569 ◽  
Author(s):  
M K Salo ◽  
E Vartiainen ◽  
P Puska ◽  
T Nikkari

SummaryPlatelet aggregation and its relation to fatty acid composition of platelets, plasma and adipose tissue was determined in 196 randomly selected, free-living, 40-49-year-old men in two regions of Finland (east and southwest) with a nearly twofold difference in the IHD rate.There were no significant east-southwest differences in platelet aggregation induced with ADP, thrombin or epinephrine. ADP-induced platelet secondary aggregation showed significant negative associations with all C20-C22 ω3-fatty acids in platelets (r = -0.26 - -0.40) and with the platelet 20: 5ω3/20: 4ω 6 and ω3/ ω6 ratios, but significant positive correlations with the contents of 18:2 in adipose tissue (r = 0.20) and plasma triglycerides (TG) (r = 0.29). Epinephrine-induced aggregation correlated negatively with 20: 5ω 3 in plasma cholesteryl esters (CE) (r = -0.23) and TG (r = -0.29), and positively with the total percentage of saturated fatty acids in platelets (r = 0.33), but had no significant correlations with any of the ω6-fatty acids. Thrombin-induced aggregation correlated negatively with the ω3/6ω ratio in adipose tissue (r = -0.25) and the 20: 3ω6/20: 4ω 6 ratio in plasma CE (r = -0.27) and free fatty acids (FFA) (r = -0.23), and positively with adipose tissue 18:2 (r = 0.23) and 20:4ω6 (r = 0.22) in plasma phospholipids (PL).The percentages of prostanoid precursors in platelet lipids, i. e. 20: 3ω 6, 20: 4ω 6 and 20 :5ω 3, correlated best with the same fatty acids in plasma CE (r = 0.32 - 0.77) and PL (r = 0.28 - 0.74). Platelet 20: 5ω 3 had highly significant negative correlations with the percentage of 18:2 in adipose tissue and all plasma lipid fractions (r = -0.35 - -0.44).These results suggest that, among a free-living population, relatively small changes in the fatty acid composition of plasma and platelets may be reflected in significant differences in platelet aggregation, and that an increase in linoleate-rich vegetable fat in the diet may not affect platelet function favourably unless it is accompanied by an adequate supply of ω3 fatty acids.


LWT ◽  
2021 ◽  
pp. 110867
Author(s):  
Min Hyeock Lee ◽  
Ha Ram Kim ◽  
Woo Su Lim ◽  
Min-Cheol Kang ◽  
Hee-Don Choi ◽  
...  

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