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

Abstract

This study aims to determine how glucagon intervenes in the regulation of fuel metabolism, especially lipolysis, at two stages of a spontaneous long-term fast characterized by marked differences in lipid and protein availability and/or utilization (phases II and III). Changes in the plasma concentration 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 a subantarctic bird (king penguin) before, during, and after a 2-h glucagon infusion. In the two fasting phases, glucagon infusion at a rate of 0.025 g ⅐ kg Ϫ1 ⅐ min Ϫ1 induced a three-to fourfold increase in the plasma concentration and in the rate of appearance (R a) of glycerol and nonesterified fatty acids, the percentage of primary reesterification remaining unchanged. Infusion of glucagon also resulted in a progressive elevation of the plasma concentration of glucose and ␤-hydroxybutyrate and in a twofold higher insulinemia. These changes were not significantly different between the two phases. The plasma concentrations of triacylglycerols and uric acid were unaffected by glucagon infusion, except for a 40% increase in plasma uric acid in phase II birds. Altogether, these results indicate that glucagon in a long-term fasting bird is highly lipolytic, hyperglycemic, ketogenic, and insulinogenic, these effects, however, being similar in phases II and III. The maintenance of the sensitivity of adipose tissue lipolysis to glucagon could suggest that the major role of the increase in basal glucagonemia observed in phase III is to stimulate gluconeogenesis rather than fatty acid delivery. lipolysis; ketone bodies; glucose; isotopic tracers; seabirds MAMMALS AND BIRDS adjust to long-term fasting by mobilizing their fat stores and sparing body proteins (8,14,21). However, the conservation of body protein that characterizes the so-called phase II of fasting is no longer maintained when a lower threshold of fat stores is reached. Then a metabolic shift occurs, and animals enter a new fasting state (phase III) corresponding to a simultaneous acceleration in the catabolism of protein and a decrease in the contribution of lipid to energy production (21, 46). This shift has been described in experimentally fasted laboratory mammals (21, 34) and in birds that spontaneously fast for prolonged periods at certain stages of their annual cycle, such as penguins (23, 37). Nevertheless, the way the metabolic shift is triggered and how the utilization of the metabolic fuels is regulated during phase II and phase III are poorly understood.Among the various hormones that could intervene to regulate fuel utilization, glucagon is likely to play a major role. Although the evidence for a lipolytic action in humans is scarce (10), glucagon stimulates lipolysis in vitro in mammals (38,52) and is the main lipolytic hormone in birds (9,22,36). It therefore plays a key role in the mobilization of fatty acids (FA) from adipose tissue. In mammals, glucagon also appears to influen...

In vivoregulation of rainbow trout lipolysis by catecholamines

“…R a glycerol is recognized as the best estimate of lipolysis, and it has been widely used to quantify whole-body lipolytic rates in vertebrates, including mammals Wolfe, 1992;Weber et al, 1993;McClelland et al, 2001;Henderson et al, 2007;Houser et al, 2007), birds (Bernard et al, 2002;Bernard et al, 2003;Vaillancourt and Weber, 2007) and fish (Bernard et al, 1999). Using R a glycerol for this purpose is recommended because the glycerol produced by lipolysis must obligatorily appear in the circulation, in situ recycling being prevented by the negligible activities of glycerol kinase in the adipose tissue and muscle of vertebrates (Newsholme and Taylor, 1969;Brooks et al, 1982;Reshef et al, 2003).…”

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

“…A priming dose of labelled glycerol equivalent to 30·min of infusion was administered before starting the actual infusion. This protocol ensured that isotopic steady state was reached in less than 40·min (Bernard et al, 2002a;Bernard et al, 2003). Blood samples (450·l each) were drawn from the arterial catheter 50 and 60·min after starting the infusion to determine glycerol kinetics under thermoneutral conditions (22°C).…”

“…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.…”

“…mitochondria. Mobilization of fat stores, or lipolysis, has been measured as the rate of appearance of glycerol (R a glycerol) in many species including humans (Beylot et al, 1987), other mammals (Himms-Hagen, 1968;Kalderon et al, 2000;McClelland et al, 2001;Shaw et al, 1975;Weber et al, 1993), rainbow trout (Bernard et al, 1999), and one bird: the king penguin (Bernard et al, 2002a;Bernard et al, 2003). R a glycerol can only be measured by continuous infusion of labelled glycerol, and it is therefore not surprising that avian lipolytic rate is only known for large (>13·kg), easy-going penguins.…”