Changes In Rates Of Lipolysis Research Articles

Butyrate and other short-chain fatty acids increase the rate of lipolysis in 3T3-L1 adipocytes.

We determined the effect of butyrate and other short-chain fatty acids (SCFA) on rates of lipolysis in 3T3-L1 adipocytes. Prolonged treatment with butyrate (5 mM) increased the rate of lipolysis approximately 2–3-fold. Aminobutyric acid and acetate had little or no effect on lipolysis, however propionate stimulated lipolysis, suggesting that butyrate and propionate act through their shared activity as histone deacetylase (HDAC) inhibitors. Consistent with this, the HDAC inhibitor trichostatin A (1 µM) also stimulated lipolysis to a similar extent as did butyrate. Western blot data suggested that neither mitogen-activated protein kinase (MAPK) activation nor perilipin down-regulation are necessary for SCFA-induced lipolysis. Stimulation of lipolysis with butyrate and trichostatin A was glucose-dependent. Changes in AMP-activated protein kinase (AMPK) phosphorylation mediated by glucose were independent of changes in rates of lipolysis. The glycolytic inhibitor iodoacetate prevented both butyrate- and tumor necrosis factor-alpha-(TNF-α) mediated increases in rates of lipolysis indicating glucose metabolism is required. However, unlike TNF-α– , butyrate-stimulated lipolysis was not associated with increased lactate release or inhibited by activation of pyruvate dehydrogenase (PDH) with dichloroacetate. These data demonstrate an important relationship between lipolytic activity and reported HDAC inhibitory activity of butyrate, other short-chain fatty acids and trichostatin A. Given that HDAC inhibitors are presently being evaluated for the treatment of diabetes and other disorders, more work will be essential to determine if these effects on lipolysis are due to inhibition of HDAC.

High-altitude acclimation increases the triacylglycerol/fatty acid cycle at rest and during exercise.

High-altitude acclimation alters lipid metabolism during exercise, but it is unknown whether this involves changes in rates of lipolysis or reesterification, which form the triacylglycerol/fatty acid (TAG/FA) cycle. We combined indirect calorimetry with [2-(3)H]glycerol and [1-(14)C]palmitate infusions to simultaneously measure total lipid oxidation, lipolysis, and rate of appearance (R(a)) of nonesterified fatty acids (NEFA) in high-altitude-acclimated (HA) rats exercising at 60% maximal O(2) uptake (VO(2 max)). During exercise, relative total lipid oxidation (%VO(2)) equaled sea-level control (SL) values; however, acclimation greatly stimulated lipolysis (+75%) but had no effect on R(a) NEFA. As a result, TAG/FA cycling increased (+119%), due solely to an increase in recycling (+144%) within adipocytes. There was no change in either group in these variables with the transition from rest to exercise. We conclude that, in HA, 1) acclimation is a potent stimulator of lipolysis; 2) rats do not modify TAG/FA cycling with the transition to exercise; and 3) in normoxia, HA and SL derive the same fraction of their total energy from lipids and carbohydrates.

No effect of the Trp64Arg beta 3-adrenoceptor variant on in vivo lipolysis in subcutaneous adipose tissue.

A Trp64Arg variant in the human beta 3-adrenoceptor is associated with earlier onset of non-insulin-dependent diabetes mellitus and obesity in several populations. The present study investigated in vivo lipolysis in individuals homozygous for the 'variant' allele coding for arginine (Arg) in position 64 of the beta 3-adrenoceptor or homozygous for the 'wild type' tryptophan (Trp) allele. Subjects were 25 healthy, non-diabetic Pima Indians, 8 Arg (2 males, 6 females; aged 34 +/- 9 years, BMI 36.2 +/- 7.7 kg/m2, 43 +/- 11% body fat [mean +/- SD]), and 17 Trp (9 males, 8 females; aged 30 +/- 5 years, BMI 30.4 +/- 6.1 kg/m2, 39 +/- 9% body fat). After an overnight fast, a microdialysis probe was inserted in the subcutaneous adipose tissue and perfused with Ringer's solution. Dialysate was collected in 10-min fractions during a 30-min baseline and during 40 min with isoproterenol, a non-selective beta-adrenergic agonist, added to the perfusate (1 mumol/l). Changes in rate of lipolysis were assessed as changes in dialysate glycerol concentration. The relative changes in dialysate glycerol concentrations in response to isoproterenol, expressed as percent over baseline, were similar in the two groups (i.e. 63 +/- 30 and 74 +/- 28% in the Arg and Trp subjects, respectively). The results were also similar in the two groups after adjustment for sex and percentage of body fat. No differential effect of isoproterenol on blood flow was demonstrated between the two groups (assessed by the ethanol dilution technique). These results are consistent with in vitro studies showing no functional effect of the beta 3-adrenoceptor variant, and/or indicate that the beta 3-adrenoceptor is not very important for subcutaneous adipose tissue lipolysis.

Effect of fasting on free fatty acid, glycerol and cholesterol concentrations in blood plasma and lipoprotein lipase activity in adipose tissue of cattle.

Contributing factors in the regulation of triglyceride deposition in and fatty acid release from bovine adipose tissue were investigated. Six Holstein steers were fasted for 9 days and then refed for 41 days. Blood samples from the jugular vein and adipose tissue samples from backfat biopsies were taken during fasting and refeeding periods. Concentrations of plasma free fatty aids, glycerol and cholesterol and activity of lipoprotein lipase in adipose tissue from fasted and refed steers were measured. Plasma free fatty acid concentration increased almost eightfold during fasting. After 4 days of refeeding, free fatty acids in plasma had returned to basal concentration. Fasting had no effect on plasma cholesterol concentration; during refeeding, concentration decreased slightly and then returned to the basal concentration. Lipoprotein lipase activity decreased to 37% of the basal concentration during fasting and increased to 100% above prefasting values during refeeding. Significant changes in plasma free fatty acid and glycerol concentrations and in activity of lipoprotein lipase in adipose tissue during fasting and refeeding suggest that fatty acid mobilization and triglyceride uptake by adipose tissue of cattle adapt to great changes in energy intake. Correlations of measured blood metabolites in fasted and refed steers demonstrate that changes in rates of lipolysis and of triglyceride uptake by adipose tissue vary in a reciprocal manner.

Perifused Fat Cells: EFFECT OF LIPOLYTIC AGENTS

Abstract In vitro methods currently utilized for the determination of lipolytic responses in adipose tissue have not allowed for the continuous monitoring of rapid successive changes in rates of lipolysis. The perifused fat cell system utilized in this investigation offers a simple, reproducible method by which minute-to-minute changes in the rate of lipolysis of isolated fat cells may be monitored. In this technique, isolated fat cells are placed in a plastic column and perifused with albumin-containing buffer in the absence and presence of various lipolytic agents. Using this technique, we have been able to observe alterations in the rates of glycerol release during the initiation of hormone-induced lipolysis. In addition, we have been able to observe the decline in glycerol release following the removal of the lipolytic hormone. In the perifused fat cell system, epinephrine, isoproterenol, and norepinephrine elicited a maximal lipolytic response at 10 µm, theophylline at 1 mm, and glucagon at 5 µm. In addition, N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (1 mm), adrenocorticotropic hormone (100 milliunits per ml), and thyroid stimulating hormone (75 milliunits per ml) effectively stimulated lipolysis in the perifused fat cell system, whereas cyclic adenosine 3':5'-monophosphate (1 mm) and serotonin (1 mm) were without effect. Unlike the incubated tissue method, growth hormone (20 µg per ml) was found to be a potent stimulator of lipolysis in this system. The combined administration of theophylline and epinephrine, both at submaximal concentrations, resulted in rates of glycerol release which were significantly greater than the sum of the rates observed during individual administration.