Jean-Michel Weber - Research
ANIMAL ENERGETICS LAB
Department of Biology
University of Ottawa
Our research deals with all aspects of animal energetics. Focus has been on how animals and humans manage energy reserves and how they select an appropriate mix of metabolic fuels to cope with extreme situations. We carry out experiments where endurance exercise, cold exposure, prolonged fasting or environmental hypoxia are used to manipulate the rate of energy expenditure of the whole organism. The goal is to integrate molecular, cell, tissue, and organismal information to understand the design of energy supply pathways. We often use experimental models showing extraordinary capacity for energy flux, either very low or unusually high. Recently, we have been particularly interested in the metabolic adaptations of long-distance migrants.
Background on energy metabolism
Weber J-M (1999). Energy cycle in vertebrates: From food to ATP. In Nature Encyclopedia of Life Sciences. John Wiley & Sons Ltd, Chichester.
Regulating metabolic fuel selection
Weber J-M (2011). Metabolic fuels: regulating fluxes to select mix. J. Exp. Biol. 214: 286-294.
Physiological adaptations of long-distance migrants
Weber J-M (2009). The physiology of long-distance migration: extending the limits of endurance metabolism.
J. Exp. Biol. 212: 593-597.
NATURAL DOPING IN LONG-DISTANCE MIGRANT BIRDS
Long-distance migrant birds rely on lipids as their main energy source for flight, but alternative roles for this essential fuel had not been considered. We thought that dietary lipids could also be used as performance-enhancing substances to prepare animals for migration. The semipalmated sandpiper (Calidris pusilla) provides a unique model to study the effects of nutrition on the metabolism of long-distance migrants and on their exercise capacity. This fascinating species stops in the Bay of Fundy (New Brunswick, Canada) during its fall migration from the Arctic to South America. Over a 2 week period, it doubles body mass, from ~20 to 40 g, by feeding exclusively on small burrowing shrimps (Corophium volutator) before a 3-day, non-stop flight over the Atlantic. This mudshrimp is an extremely rich source of the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that are known to boost aerobic capacity and to have many beneficial health effects in humans (more generally known as omega-3 fatty acids). We have used refueling sandpipers as a natural experiment to test our hypothesis. Results show that n-3 fatty acids from Corophium are rapidly incorporated in the birds flight muscles, making their membranes more fluid and improving their ability for fatty acid transport. During refueling, mitochondrial density of flight muscles increases, together with the activities of key enzymes of oxidative metabolism that are, in turn, correlated with changes in n-3 PUFA content. The dietary n-3 PUFA of semipalmated sandpipers are not simply an important energy source, but a potent metabolic signal to improve muscle performance. These studies show that some migrant birds use natural diets rich in specific lipids to prime their flight muscles for endurance exercise.
More recently, we have fed EPA and DHA to bobwhite quails, a sedentary bird species that never migrates. The incorporation of these n-3 fatty acids in the quail diet caused a 58-90% increase in the activities of key oxidative enzymes in flight muscle. Therefore, these dietary lipids can boost the aerobic capacity of muscle to the same extent as extreme endurance training,...but without any exercise!
This discovery has significant implications:
a) for improving fundamental knowledge of metabolism
b) for widlife conservation of migrant birds
c) for research on natural means to increase the performance of human athletes, and
d) for research on human obesity
(the regulation of a 2-fold, reversible change in body mass is instructive for physiologists and physicians alike).
Nagahuedi S, Popesku JT, Trudeau VL & J-M Weber (2009). Mimicking the natural doping of migrant sandpipers in sedentary quails: effects of dietary n-3 fatty acids on muscle membranes and PPAR expression.
J Exp Biol 212: 1106-1114
See comments in SCIENCE SCIENTIFIC AMERICAN INSIDE JEB
Maillet D & J-M Weber (2006). Performance-enhancing role of dietary fatty acids in a long-distance migrant: The semipalmated sandpiper. J Exp Biol 209: 2686-2695
See “Filling Up on Fats” (Editors’ Choice) in SCIENCE
Maillet D & J-M Weber (2007). Relationship between n-3 PUFA content and energy metabolism in the flight muscles of a migrating shorebird: evidence for natural doping. J Exp Biol 210: 413-420
Vaillancourt E & J-M Weber (2007). Lipid mobilization of long-distance migrant birds in vivo: the high lipolytic rate of ruff sandpipers is not stimulated during shivering. J Exp Biol 210: 1161-1169
Scroll down to “Fast food” in SCIENCE and see “Fat processing champions” in INSIDE JEB
Semipalmated sandpiper, Calidris pusilla
Flock of semipalmated sandpipers in the Bay of Fundy
Mudshrimp (Corophium volutator) burried in mud
Male and female mudshrimp, Corophium volutator (S. Mautner)
Heat exchange has been thoroughly studied in humans exposed to cold, but the relative use of various metabolic fuels for heat production has received little attention in comparison. We have used a combination of stable isotope tracer methods, indirect calorimetry and electromyography (EMG) to quantify the thermogenic contributions of different oxidative substrates in shivering humans. During prolonged, low-intensity shivering, we have established that heat production is unequally shared among lipids (50%), muscle glycogen (30%), circulating glucose (10%) and proteins (10%). We have also investigated the impact of large changes in glycogen reserves on fuel selection. Glycogen-depleted and glycogen-loaded subjects are able to sustain the same thermogenic rate, but they oxidize drastically different fuel mixtures (27 vs 65% of total heat generated from carbohydrates). Normal heat production of glycogen-depleted individuals is not compromised because lipids and proteins increase their contribution to compensate. We have developed new methods for the simultaneous measurement of shivering pattern (detailed analysis of EMG spectral parameters) and fuel selection. During low-intensity shivering, humans are able to maintain heat balance by oxidizing widely different fuel mixtures within the same muscle fibers. Surprisingly, the alternative mechanism of fuel selection is used during intense shivering: the recruitment of different populations of “fuel-specific fibers”. We have shown for the first time that the EMG signature of active muscles contains important quantitative information on oxidative fuel metabolism. Differences in “burst shivering rate” (high-intensity shivering of low frequency) closely reflect differences in carbohydrate oxidation. We have also determined that the fuel selection patterns of shivering and exercise are surprisingly different. At the same power output, a muscle producing only heat (shivering), or significant movement (exercise) strikes a different balance between lipid and carbohydrate oxidation. We concluded that burst shivering is a crucial component of the thermogenic response because it coordinates fuel selection and, therefore, it could play an essential role in limiting human survival in cold environments.
For a summary of our research on shivering humans: Physiology News No. 58: 26-27, spring 2005.
Haman F, Péronnet F, Kenny GP, Massicotte D, Lavoie C & Weber J-M. (2005). Partitioning oxidative fuels during cold exposure: Muscle glycogen becomes dominant as shivering intensifies. J Physiol (London) 566.1, 247-256.
GENERAL MODEL OF FUEL SELECTION
Our work on substrate metabolism has allowed to formulate a general model of fuel selection for exercising mammals. Metabolic rate - expressed in relation to the aerobic maximum (%VO2 max) – determines the relative contributions of lipids and carbohydrates to total metabolism. We have tested the robustness of this statement by comparing animals of different aerobic capacities: 1) sedentary vs highly aerobic species, 2) small vs large body size, and 3) normoxia- vs hypoxia-acclimated. Results show that this general fuel selection model is independent of VO2 max when tested for: adaptive variation, allometric variation, and environmental variation in O2 availability. Because all exercising mammals measured to date comply with the model, muscles that clearly deviate from it may be useful tools to decipher fundamental characteristics of fuel selection mechanisms. This is what prompted our investigation of shivering humans (whose muscles use far more carbohydrates than predicted by the mammalian exercise model) and long-distance migrant birds (that use far more lipids).
Weber J-M & Haman F. (2004). Oxidative fuel selection: adjusting mix and flux to stay alive. In Animals and Environments, ed. Morris S & Vosloo A, pp. 22-31. Elsevier, Amsterdam.
DESIGN OF THE OXYGEN AND SUBSTRATE PATHWAYS
NOVEL PHYSIOLOGICAL ROLE FOR LEPTIN
Leptin maintains normal body weight by modulating energy intake and expenditure. The size of fat reserves is “self-regulated” by leptin released from adipocytes. Plasma leptin levels vary with the size of adipose reserves and acts as an internal signal for the energy status of the animal. We have discovered a new physiological link between leptin, substrate cycling, and total energy expenditure, that could play a key role in the natural prevention of obesity. Lipolysis of triacylglycerol (TAG) stores releases fatty acids (FA) either for oxidation or reesterification (TAG re-synthesis). Simultaneous lipolysis and reesterification form the TAG/FA cycle, a substrate cycle that dissipates energy. Concurrent flux through these opposing reactions forms a futile cycle that uses ATP for thermogenesis without net conversion of substrate to product. We have shown that leptin causes strong activation of TAG/FA cycling, lipolysis, and FA oxidation, and that it shifts fuel preference from carbohydrates to lipids. The stimulation of substrate cycling is therefore a potent new mechanism triggered by leptin to decrease metabolic efficiency when lipid stores are in excess. Before these studies, increased expression of uncoupling proteins was the only other known mechanism by which leptin seemed to stimulate metabolic rate. We have characterized a different pathway used by this hormone to adjust energy expenditure for the maintenance of normal body weight.
University of Ottawa Gazette: Unravelling the mysteries of fat burning hormones by Marlene Orton
FUEL METABOLISM IN SALMONID FISH
Our lab was the first to develop and validate methods to measure metabolite fluxes of fish in vivo. This was triggered by the realization that many fish studies report changes in metabolite concentrations, but use them to draw erroneous conclusions about fluxes. We have implemented new methods to quantify rates of glucose, glycerol, fatty acid and triacylglycerol turnover in fish. These tools have allowed to characterize the effects of exercise, hypoxia and selected hormones on the fluxes of metabolic fuels. We have recently demonstrated that salmonid fish use circulating lipoproteins as their main oxidative fuel to support prolonged swimming.
Double catheterization method to measure fluxes of metabolic substrates
Haman F & Weber J-M. (1996). Continuous tracer infusion to measure in vivo metabolite turnover rates in trout. J Exp Biol 199, 1157-1162.
Haman F, Powell M & Weber J-M. (1997). Reliability of continuous tracer infusion for measuring glucose turnover rate in rainbow trout. J Exp Biol 200, 2557-2563.
(photos by A. Morin)