Selective mobilization of fatty acids from adipose tissue triacylglycerols

Adipose tissue triacylglycerols represent the main storage of a wide spectrum of fatty acids differing by molecular structure. The release of individual fatty acids from adipose tissue is selective according to carbon chain length and unsaturation degree in vitro and in vivo in animal studies and also in humans. The mechanism of selective fatty acid mobilization from white fat cells is not known. Lipolysis is widely reported to work at a lipid-water interface where only small amounts of substrate are available. A preferential hydrolysis of a small triacylglycerol fraction enriched in certain triacylglycerol molecular species at the lipid-water interface and enzymological properties of hormone-sensitive lipase could explain the selective mobilization of fatty acids from fat cells. This selectivity could affect the individual fatty acid supply to tissues.     

Selective mobilization of fatty acids in adipose tissue of heavy pigs

The mobilization of fatty acids during food deprivation is a selective process studied in different species (humans, rodents, birds, viverrids). The aim of this work was to study the effect of fasting on selective mobilization in commercial pigs. A total of 16 barrows (Large White×Landrace (167 kg±12.5 kg live weight) were subdivided into two homogeneous groups, one subjected to 12 h and the other to 60 h of fasting (fasting time) before slaughtering. For each pig inner and outer backfat layer were sampled at slaughter and at ham trimming 24 h later (sampling time). Increasing the fasting time and the sampling time after slaughter caused an increase in the amount of free fatty acids in both layers. Therefore it can be argued that during fasting lipolysis is stimulated and remains active also after slaughtering. The factors that stimulate lipolysis determine a greater mobilization of unsaturated fatty acids than saturated ones. Thus fasting time may influence the suitability of pork for processing and conservation, since free fatty acids are more suitable for oxidation than the esterified ones.     

Ledakrin effect on free fatty acid and glycerol mobilization from epididymal adipose tissue of rat in vitro

It was demonstrated that Ledakrin, an antitumour drug, causes mobilization of free fatty acids and glycerol from the epididymal adipose tissue of rat in vitro. The disproportion observed in the release of glycerol and free fatty acids following Ledakrin administration suggested a biphasic effect of this drug, with initial stimulation and later inhibition of the processes of lipolysis and lipogenesis. Blockade of adrenergic membrane receptors (with propranolol or regitine) abolished the lipolytic effect of Ledakrin.     

Hepatic triglyceride secretion in relation to lipogenesis and free fatty acid mobilization in fasted and glucose-refed rats

Plasma triglyceride concentrations were significantly lowered by a single feeding of glucose to rats that had been fasted for 22 hr. Three feedings of glucose produced a similar effect. In the glucose-refed animals mobilization of free fatty acids from adipose tissue was impaired more rapidly than hepatic lipogenesis was restored from its low fasting level. These effects of glucose were shown by both a 50% fall in plasma free fatty acid concentration and an 84% decrease in free fatty acid release by isolated epididymal fat pads within 30 min after a single refeeding of glucose. Hepatic lipogenesis from either acetate-1-(14)C or glucose-U-(14)C was not restored even after glucose had been fed three times at hourly intervals. Triton-induced hypertriglyceridemia was used to measure the hepatic triglyceride secretory rate; it was found that glucose refeeding decreased this rate in all but one of several experiments. This decreased secretion rate was sufficient to account for the nearly complete disappearance of triglyceride in very low density lipoproteins (d < 1.019) that occurred within 1 hr after a single glucose intubation.     

A role for hormone-sensitive lipase in the selective mobilization of adipose tissue fatty acids.

The mobilization of fatty acids from rat and human fat cells is selective according to molecular structure, and notably carbon atom chain length. This study aimed at examining whether the release of individual fatty acids from triacylglycerols (TAG) by hormone-sensitive lipase (HSL) plays a role in the selectivity of fatty acid mobilization. Recombinant rat and human HSL were incubated with a lipid emulsion. The hydrolysis of 18 individual fatty acids, ranging in chain length from 12 to 24 carbon atoms and in unsaturation degree from 0 to 3 double bond(s), was measured by comparing the composition of non-esterified fatty acids (NEFA) to that of the original TAG. The relative hydrolysis (% in NEFA/% in TAG) differed between fatty acids, being about 5-fold and 3-fold higher for the most (18:1n-7) than for the least (24:0) readily released fatty acid by recombinant rat and human HSL, respectively. Relationships were found between the chain length of fatty acids and their relative hydrolysis. Among 12-24 carbon atom saturated fatty acids, the relative hydrolysis markedly decreased (by about 5- and 3-times for recombinant rat and human HSL, respectively) with increasing chain length. We conclude that fatty acids are selectively released from TAG by HSL according to carbon atom chain length. These data provide insight on the mechanism by which fatty acids are selectively mobilized from fat cells.     

Essential fatty acids in adipose tissue

Among the numerous causes of lipomobilization of fatty acids from the adipose tissue it is also carbon tetrachloride (CCl4). The research shows that the saturated fatty acids decreased in this tissue of the rats injected with CCl4, even if the linolenic and alpha-linolenic acids are present in the diet.     

Effect of glucocorticoid hormones on fatty acid mobilization and re-esterification in rat adipose tissue

1. The effect of dexamethasone and cortisol on fatty acid mobilization and re-esterification has been studied in intact adipose tissue and isolated fat cells of the rat. 2. Dexamethasone added in vitro inhibited both the re-esterification of mobilized free fatty acids and the esterification of palmitate in the medium. 3. Under several conditions (low concentrations of dexamethasone, cortisol at a high concentration, with tissue from starved animals), steroid-induced release of free fatty acids could be accounted for by decreased re-esterification only, overall lipolytic activity remaining unmodified. At higher concentrations of dexamethasone, however, stimulation of lipolytic activity also occurred. 4. Decreased re-esterification produced by dexamethasone was observed in the total absence of glucose from the incubation medium. Further, dexamethasone stimulated the disappearance of prelabelled [(14)C]glycogen from the tissue. 5. The evidence presented suggests that mobilization of free fatty acids induced by glucocorticoid hormones under physiological conditions is primarily due to a decrease of the re-esterification rate rather than to lipase activation.     

Uptake of serum free fatty acids by lipids of the brown adipose tissue]

The flow rate of serum free fatty acids (FFA) into the lipids of brown adipose tissue (BAT) of newborn rabbits was determined by intravenous injection of [14C]-1-palmitate. For a normal 7 day old animal during acute cold exposure the flow rate is (1 hour in 20 degrees C ambient temperature) 0.209 mumol/minute, that is 3.6% of the serum FFA turnover. Prolonged cold exposure only induced an increase in FFA influx if the lipid depot had been depleted (48 hours starvation in 20 degrees C). Consequently, the BAT takes up serum FFA for heat production only after mobilisation of its lipid stores. It is supposed that the mechanism of the uptake of serum FFA by the BAT is connected with their esterification to triglycerides. The phospholipids of BAT which are not only membrane bound lipids are characterized by a high metabolism.     

Studies on triglyceride lipases from rat adipose tissue.

A new assay procedure for triglyceride lipase [EC 3.1.1.3] was developed in which radioactive triolein was dissolved in ethanol and directly added to the reaction mixture in the absence of serum and albumin. In the rat adipose tissue there appeared to be a triglyceride lipase measurable with this assay in addition to the two previously defined lipases, lipoprotein lipase [EC 3.1.1.34] and hormone-sensitive lipase. The enzyme was active in the absence of serum and was strongly inhibited by albumin. The molecular weight was estimated to be about 42,000. Adenosine 3',5'-monophosphate-dependent protein kinase [EC 2.7.1.27] was unable to activate the enzyme. The three species of lipases mentioned above behaved differently upon chromatography on a Sepharose 4B column, and were distinguishable from each other in their physical and kinetic properties. The physiological roles of the new species of lipase remain to be explored.     

Transport and metabolism of extracellular free fatty acids in adipose tissue of fed and fasted mice

We used a new tracer technique, direct tracer injection of [1-14C]palmitate-serum albumin into extracellular fluid (ECF) of epididymal fat pads, to study relative transport rates of ECF-free fatty acids (FFA) to cell-FFA and subsequent esterification to diglyceride fatty acid (DGFA) and triglyceride fatty acid (TGFA) in adipose tissue versus movement of ECF- and cell-FFA into the circulation of mice fed ad libitum or fasted 48 hr. Radioactivity was measured in the following fractions at varying times (for 1 hr): ECF-FFA, cell-FFA, cell-DGFA, cell-TGFA, plasma-FFA (total lipids), and breath CO2. Pool sizes of ECF-FFA, cell-FFA, cell-TGFA, and plasma-FFA were determined. Analysis by multicompartmental methods (SAAM) indicates that the ECF-FFA compartment of epididymal fat pads is in a relatively rapid exchange with a cellular-FFA compartment, but neither is in direct, nor appreciably rapid, communication with circulating FFA. FFA is rapidly esterified in adipocytes of fed mice, but esterification is significantly inhibited in mice fasted for 48 hr. In both dietary states, essentially all labeled FFA appearing in the circulation was derived from ECF-FFA that were first transferred to the cell, esterified to TGFA, then hydrolyzed to FFA before being transported to the circulation.