Energy metabolism in trauma and sepsis: the role of fat.
There seems little doubt that there are signals for the increased mobilization of fat in shock, trauma, and sepsis. Whether those signals are reflected by an actual increase in mobilization is dependent on many variables including cardiovascular status. A hypothetical scheme based on our own experiments in the hyperdynamics phases of response to burn injury and to sepsis is presented in Figure 8. According to this scheme, catecholamines stimulate lipolysis in the adipose tissue, resulting in the release of glycerol and FFA into the plasma at increased rates. The glycerol is cleared by the liver and converted into glucose--a process stimulated by, among other things, glucagon. Some of the increased flux of FFA is also cleared by the liver, whereupon the fatty acids are incorporated into VLDL and released again into the plasma. The increased FFA levels also exert a dampening effect on the factors stimulating hepatic glucose production. At the periphery, plasma FFA as well as VLDL fatty acids are taken up at an increased rate. The tissues are attuned to the oxidation of fat, and as a consequence most of the energy production is derived from fat oxidation. The increased fatty acids exert an inhibitory effect on the complete oxidation of glucose, so although glucose may be taken up at an accelerated rate, the relative contribution of glucose oxidation to total energy production may fall. Rather than being completely oxidized, pyruvate is reduced to lactate and released into the plasma at an accelerated rate. The lactate then contributes to the production of glucose in the liver, completing a cyclical process called the Cori Cycle. Although all aspects of this scheme are supported by data highlighted in this paper, it certainly must be an oversimplification of the overall response of substrate metabolism to trauma and sepsis. It is presented for the purpose of highlighting the potential role of fat as a controller of the metabolic response, and to suggest that the enhanced mobilization and oxidation of fat is one of the fundamental responses to stress.
D000818:Animals; D002056:Burns / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal / Q000378:metabolism; D004285:Dogs; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D012769:Shock / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism; D012774:Shock, Traumatic / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology
D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D005947:Glucose