Blockade of fatty acid oxidation mimics phase II-phase III transition in a fasting bird, the king penguin

Abstract

This study tests the hypothesis that the metabolic and endocrine shift characterizing the phase II-phase III transition during prolonged fasting is related to a decrease in fatty acid (FA) oxidation. Changes in plasma concentrations of various metabolites and hormones and in lipolytic fluxes, as determined by continuous infusion of [2-3 H]glycerol and [1-14 C]palmitate, were examined in vivo in spontaneously fasting king penguins in the phase II status (large fat stores, protein sparing) before, during, and after treatment with mercaptoacetate (MA), an inhibitor of FA oxidation. MA induced a 7-fold decrease in plasma ␤-hydroxybutyrate and a 2-to 2.5-fold increase in plasma nonesterified fatty acids (NEFA), glycerol, and triacylglycerols. MA also stimulated lipolytic fluxes, increasing the rate of appearance of NEFA and glycerol by 60-90%. This stimulation might be partly mediated by a doubling of circulating glucagon, with plasma insulin remaining unchanged. Plasma glucose level was unaffected by MA treatment. Plasma uric acid increased 4-fold, indicating a marked acceleration of body protein breakdown, possibly mediated by a 2.5-fold increase in circulating corticosterone. Strong similarities between these changes and those observed at the phase II-phase III transition in fasting penguins support the view that entrance into phase III, and especially the end of protein sparing, is related to decreased FA oxidation, rather than reduced NEFA availability. MA could be therefore a useful tool for understanding mechanisms underlying the phase II-phase III transition in spontaneously fasting birds and the associated stimulation of feeding behavior.protein sparing; lipolytic fluxes; isotopic tracers; mercaptoacetate; seabirds PROLONGED FASTING IS CHARACTERIZED by the preferential utilization of lipid, with relative sparing of body protein (4, 6, 25). Previous studies indicated that protein sparing depends on the availability of lipid fuels (17). The conservation of body protein that characterizes the so-called phase II of fasting (9, 17) is no longer maintained when a lower threshold in fat stores is reached (6,17,22,25). Then a metabolic shift occurs, with a simultaneous acceleration in the catabolism of body protein and a decrease in the contribution of lipid to energy production, the signature of the so-called phase III of fasting (6,22,25). Entrance into phase III is also accompanied by hormonal changes, such as an increase in the level of circulating glucocorticoids thought to contribute to the stimulation of protein breakdown (10). How fat store availability determines body protein sparing during phase II or accelerated catabolism during phase III is not well understood. Is protein sparing during phase II linked to the availability of nonesterified fatty acids (NEFA) mobilized from adipose tissue, or does it depend on their oxidation? Arguments suggest that NEFA may specifically modulate the breakdown of myofibrillar proteins independently of their oxidation as a fuel for muscle (26). This suggestion agrees with ...

Lipolytic and metabolic response to glucagon in fasting king penguins: phase II vs. phase III

“…However, the possibility that the effects of increased basal glucagonemia could be different in some aspects from those of artificially raised glucagon levels should be examined, including using somatostatin (if effective in penguins) and replacement infusion of insulin. From previous results, we have suggested that under conditions of basal NEFA availability, entrance into phase III could be related to a decreased capacity for FA oxidation (3,4). In contrast, the present data suggest that oxidative capacity is maintained in phase III birds with highly increased NEFA availability.…”

“…The specific activities of plasma glycerol and NEFA were determined as previously described (4,5). A 1-ml aliquot of plasma was mixed with chloroform-methanol (2:1, vol/vol).…”

The role of glucocorticoids in naturally fasting grey seal (Halichoerus grypus) pups: dexamethasone stimulates mass loss and protein utilisation, but not departure from the colony

“…For example, a dramatic change in fatty acid oxidation and BUN, prolactin and glucagon concentrations occur at the same time as elevated GC levels in animals on entry into phase III (Bernard et al, 2002a;Bernard et al, 2002b;Cherel et al, 1988a;Cherel et al, 1988b;Cherel et al, 1988c;Groscolas and Robin, 2001;Le Maho et al, 1981;Robin et al, 1998). Our findings do not exclude the possibility that cortisol provides a cue to forage in seals when fat reserves are very low, such as in starvelings.…”

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

“…Overall, body size effects on metabolic rate can only explain <50% of these large differences [calculated using the classic allometric equation for resting mammals (Schmidt-Nielsen, 1990)]. 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).…”

“…The mean value plotted here for ruff sandpipers is for shivering birds (note that the mean value for non-shivering birds was even higher, although not significantly so; see Table·1). Each point is the mean value from a different study [rat (Kalderon et al, 2000;McClelland et al, 2001), rabbit (HimmsHagen, 1968;Reidy and Weber, 2002), dog Shaw et al, 1975), pigmy goat (Weber et al, 1993), sheep (Bergman, 1968), human (Bahr et al, 1990;Mora-Rodriguez et al, 2001;Wolfe et al, 1990) and king penguin (Bernard et al, 2002a;Bernard et al, 2002b;Bernard et al, 2003) . Assuming that 84% of the necessary ATP is derived from lipid oxidation (i.e.…”