Stress response: Lipolysis
Basic, Organ-Based and Clinical Sciences, Physiology
Of note, a process known as hypermetabolism may occur in the stress response. In this situation, insulin levels are actually normal to high (different from the fasting state) which leads to less ketone production. Therefore, glyceride from triglyceride breakdown enters into the gluconeogenesis cycle. However, due to insulin resistance (mediated by tumor necrosis factor alpha, IL-1, INF-alpha, and INF-gamma) there is concomitant fatty acid oxidation that which essentially results in opposing processes. Importantly, beta-oxidation is the major route of forming ATP in the stressed state. See diagrams from Miller’s Anesthesia (1), which further illustrate the process of lipolysis and the futile metabolic cycles that arise in the stressed state.
Updated definition 2020:
Stress in response to surgical stimulus, trauma, burns or critical illness results in several metabolic and physiologic responses. In regards to metabolism, we tend to see a hypermetabolic state dominated by catabolism. This is the result of several factors, including the afferent signals mediated by the hypothalamus-pituitary axis in addition to proinflammatory cytokines at the site of injury. Lipolysis occurs to help fuel the metabolic demands in the stressed state by breaking down triglycerides at peripheral adipose tissues into free fatty acids and glycerol.
The process of lipolysis is primarily driven by beta-2-adrenergic receptors responding to stimulation by catecholamines that are released during the insult. Catecholamines stimulate the beta-2-adrenergic receptor, leading to increase intracellular cAMP, resulting in activation of protein kinase A. This ultimately results in activation of lipase enzymes that break down triglycerides into free fatty acids and glycerol. The FFA that enter circulation can undergo beta-oxidation in the liver to produce ATP. The glycerol serves as a substrate for gluconeogenesis in the liver to fuel the hypermetabolic phase, which is primarily driven by the release of cortisol and growth hormone.
Insulin is secreted from beta-cells of the pancreas as a result of the hypermetabolic state, working to counteract the effects of lipolysis by promoting the anabolic state through lipogenesis and fatty acid esterification. Due to inflammatory mediators from the stress response, mainly tumor necrosis factor alpha, IL-1, INF-alpha, and INF-gamma, there is enough insulin resistance for the net effect to remain primarily catabolic.