Effects of hormones on the rate of the triacylglycerol/fatty acid substrate cycle in adipocytes and epididymal fat pads

Brooks, Brian J.; Arch, Jonathan R. S.; Newsholme, Eric A.

doi:10.1016/0014-5793(82)80945-9

Cited by 94 publications

(62 citation statements)

References 15 publications

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“…As previously described (Brooks et al 1982), insulin (10 000 µU/ml) did not alter fatty acid-TG cycling in adipocytes. No effect of leptin (10 ng/ml) or insulin plus leptin could be detected on this metabolic parameter ( Table 2).…”

Section: Effect Of Insulin Leptin and Insulin Plus Leptin On Fatty Asupporting

confidence: 62%

“…Cycling is also thought to increase sensitivity of controlling substrate flux through a metabolic pathway (Tagliaferro et al 1990). In adipocytes, glucagon and noradrenaline stimulate fatty acid-TG cycling (Brooks et al 1982). By this mechanism, intracellular fatty acids derived from TG hydrolysis are re-esterified into TG in a futile reaction, resulting in ATP consumption.…”

Section: Discussionmentioning

confidence: 99%

“…Fatty acids incorporated into TG were either newly synthesized from glucose (and thus are H-radiolabeled and represent fatty acid-TG cycling). Therefore, fatty acid-TG cycling can be calculated by the following equation (Brooks et al 1982, Tagliaferro et al 1990:…”

Section: Fatty Acid-tg Cyclingmentioning

confidence: 99%

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Leptin controls the fate of fatty acids in isolated rat white adipocytes

William

Ceddia

Curi

2002

Journal of Endocrinology

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Leptin directly increases the rate of exogenous glucose and fatty acids oxidation in isolated adipocytes. However, the effects of leptin on fatty acid metabolism in white adipose tissue have not been examined in detail. Here, we report that in adipocytes incubated for 6 h in the presence of leptin (10 ng/ml), the insulin-stimulated de novo fatty acid synthesis was inhibited by 36% (P<0·05), while the exogenous oxidation of acetic and oleic acids was increased by 50% and 76% respectively. Interestingly, leptin did not alter the oxidation of intracellular fatty acids. Leptinincubated cells presented a 16-fold increase in the incorporation of oleic acid into triglyceride (TG) and a 123% increase in the intracellular TG hydrolysis (as measured by free fatty acids release). Fatty acid-TG cycling was not affected by leptin. By employing fatty acids radiolabeled with 3 H and 14 C, we could determine the concomitant influx of fatty acids (incorporation of fatty acids into TG) and efflux of fatty acids (intracellular fatty acids oxidation and free fatty acids release) in the incubated cells. Leptin increased by 30% the net efflux of fatty acids from adipocytes. We conclude that leptin directly inhibits de novo synthesis of fatty acids and increases the release and oxidation of fatty acids in isolated rat adipocytes. These direct energy-dissipating effects of leptin may play an important role in reducing accumulation of fatty acids into TG of rat adipose cells.

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Section: Effect Of Insulin Leptin and Insulin Plus Leptin On Fatty Asupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

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Leptin controls the fate of fatty acids in isolated rat white adipocytes

William

Ceddia

Curi

2002

Journal of Endocrinology

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“…On the other hand, it has been found that about ϳ30% of the FFAs released during fasting is reesterified into triglycerides in rat adipose tissue (51,52) and as much as 40% in healthy humans (52,53). Moreover, in rat adipose tissue in vitro, the absolute rates of reesterification of FFAs are reported to increase proportionally with the rate of lipolysis (51,54,55). The reesterification of FFAs requires their acylation, a reaction catalyzed by ACS (EC 6.2.1.3).…”

Section: Discussionmentioning

confidence: 99%

AMP-activated Protein Kinase Is Activated as a Consequence of Lipolysis in the Adipocyte

Gauthier

Miyoshi

Souza

et al. 2008

Journal of Biological Chemistry

229

207

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AMP-activated protein kinase (AMPK) is activated in adipocytes during exercise and other states in which lipolysis is stimulated. However, the mechanism(s) responsible for this effect and its physiological relevance are unclear. To examine these questions, 3T3-L1 adipocytes were treated with cAMP-inducing agents (isoproterenol, forskolin, and isobutylmethylxanthine), which stimulate lipolysis and activate AMPK. When lipolysis was partially inhibited with the general lipase inhibitor orlistat, AMPK activation by these agents was also partially reduced, but the increases in cAMP levels and cAMP-dependent protein kinase (PKA) activity were unaffected. Likewise, small hairpin RNA-mediated silencing of adipose tissue triglyceride lipase inhibited both forskolin-stimulated lipolysis and AMPK activation but not that of PKA. Forskolin treatment increased the AMP:ATP ratio, and this too was reduced by orlistat. When acyl-CoA synthetase, which catalyzes the conversion of fatty acids to fatty acyl-CoA, was inhibited with triacsin C, the increases in both AMPK activity and AMP:ATP ratio were blunted. Isoproterenol-stimulated lipolysis was accompanied by an increase in oxidative stress, an effect that was quintupled in cells incubated with the AMPK inhibitor compound C. The isoproterenol-induced increase in the AMP:ATP ratio was also much greater in these cells. In conclusion, the results indicate that activation of AMPK in adipocytes by cAMP-inducing agents is a consequence of lipolysis and not of PKA activation. They suggest that AMPK activation in this setting is caused by an increase in the AMP:ATP ratio that appears to be due, at least in part, to the acylation of fatty acids. Finally, this AMPK activation appears to restrain the energy depletion and oxidative stress caused by lipolysis. AMP-activated protein kinase (AMPK)2 is a sensor of cellular energy state that responds to metabolic stresses and other regulatory signals. The mechanism of activation of AMPK is a complex phenomenon and is still not fully understood, although it is recognized that it involves phosphorylation of the critical Thr-172 residue of its ␣ catalytic subunit by upstream kinases such as LKB1, Ca 2ϩ -calmodulin-dependent protein kinase kinase, and possibly Tak1, a member of the mitogenactivated protein kinase kinase kinase family (1-5). AMPK is also regulated by AMP allosterically and the current view is that this both increases AMPK activity directly and makes it a poorer substrate for phosphatases (6).The role and regulation of AMPK in muscle, liver, and various cultured cells have been extensively studied. It is now well established that energy depletion because of starvation, hypoxia, and exercise increases the intracellular AMP:ATP ratio and secondarily AMPK activity (7). Upon its activation, a major role of AMPK is to replete cellular energy stores by stimulating processes that generate ATP, such as fatty acid oxidation, and inhibiting ATP-consuming pathways (e.g. lipogenesis, triglyceride synthesis, and gluconeogenesis) that are not acutel...

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“…Lipolytic rate is also one order of magnitude higher in sandpipers than in king penguins (Bernard et al, 2002a;Bernard et al, 2002b;Bernard et al, 2003), the only other avian species measured to date. In addition, it is clear that the values of R a glycerol reported here lie at the lower end of the range of lipolytic rates achievable by ruff sandpipers for several reasons: (1) migration flights would simply not be possible without activating lipolysis well beyond the rates measured in this study (see next paragraph); (2) the animals used here were not physiologically prepared for migration (Vaillancourt et al, 2005) and they were not acclimated to hypoxia (a treatment known to stimulate lipolytic rate) (McClelland et al, 2001); (3) ruff sandpipers were measured here only 1-5·h after the cessation of feeding whereas all the mammalian species mentioned in Fig.·5 for comparison were fasted for much longer durations (18-24·h); and (4) it has been suggested that incomplete hydrolysis of triacylglycerol may take place in bird adipose tissue (Goodridge and Ball, 1965), and significant production of mono-and diacylglycerol in bird adipocytes would make R a glycerol underestimate true lipolytic rate (a situation that does not exist in mammals) (Brooks et al, 1982). It should also be noted that the highest V O 2 value reached during shivering only represents <30% of the estimated V O 2 max of ruff sandpipers, a metabolic rate at which high rates of lipid mobilization and oxidation would be expected.…”

Section: Unusually High Lipolytic Rates In Migrant Birdsmentioning

confidence: 97%

Lipid mobilization of long-distance migrant birdsin vivo: the high lipolytic rate of ruff sandpipers is not stimulated during shivering

Vaillancourt

Weber

2007

Journal of Experimental Biology

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For long migrations, birds must rely on high flux capacities at all steps of lipid metabolism, from the mobilization of adipose reserves to fatty acid oxidation in flight muscle mitochondria. Substrate kinetics and indirect calorimetry were used to investigate key parameters of lipid metabolism in a highly aerobic shorebird: the ruff sandpiper Philomachus pugnax. In this study, we have quantified the effects of cold exposure because such measurements are presently impossible during flight. Lipolytic rate was monitored by continuous infusion of 2-[3H]-glycerol and lipid oxidation by respirometry. Plasma lipid concentrations (non-esterified fatty acids, neutral lipids and phospholipids) and their fatty acid composition were also measured to assess whether cold exposure causes selective metabolism of specific lipids. Results show that shivering leads to a 47% increase in metabolic rate (44.4±3.8 ml O2kg–1min–1 to 65.2±8.1 ml O2kg–1 min–1), almost solely by stimulating lipid oxidation (33.3± 3.3 ml O2 kg–1min–1 to 48.2±6.8 ml O2kg–1 min–1) because carbohydrate oxidation remains close to 11.5± 0.5 ml O2 kg–1min–1. Sandpipers support an unusually high lipolytic rate of 55–60 μmol glycerol kg–1 min–1. Its stimulation above thermoneutral rates is unnecessary during shivering when the birds are still able to re-esterify 50% of released fatty acids. No changes in plasma lipid composition were observed, suggesting that cold exposure does not lead to selective metabolism of particular fatty acids. This study provides the first measurements of lipolytic rate in migrant birds and shows that their capacity for lipid mobilization reaches the highest values measured to date in vertebrates. Extending the limits of conventional lipid metabolism has clearly been necessary to achieve long-distance migrations.

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Effects of hormones on the rate of the triacylglycerol/fatty acid substrate cycle in adipocytes and epididymal fat pads

Cited by 94 publications

References 15 publications

Leptin controls the fate of fatty acids in isolated rat white adipocytes

Leptin controls the fate of fatty acids in isolated rat white adipocytes

AMP-activated Protein Kinase Is Activated as a Consequence of Lipolysis in the Adipocyte

Lipid mobilization of long-distance migrant birdsin vivo: the high lipolytic rate of ruff sandpipers is not stimulated during shivering

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