Lipidomic analysis enables prediction of clinical outcomes in burn patients

Abstract

Recent discoveries have highlighted the novel metabolic functions of adipose tissue in enhancing hypermetabolism after trauma. As the exact function and expression profiles of serum lipids and free fatty acids (FFA) are essentially unknown, we determined the lipidomic expression profile after burn in correlation to clinical outcomes to identify important lipid mediators affecting post-burn outcomes. We conducted a prospective cohort study with 46 adult burn patients and 5 healthy controls at the Ross Tilley Burn Center in Toronto, Canada. Patients were stratified based on major demographic and clinical variables, including age, burn severity, mortality, and sepsis. Serum FFAs and inflammatory markers were measured during acute hospital stay. We found that FFAs were acutely elevated post-burn and returned to baseline over time. Greater burn severity and age were associated with an impaired acute response in unsaturated FFAs and pro-inflammatory cytokines. Elevations in saturated and mono-unsaturated FFAs correlated significantly to increased mortality. In summary, persistent elevation of unsaturated lipids was associated with a functionally altered inflammatory-immunological milieu and worse clinical outcomes. The present lipidomic analysis indicates profound alterations in the lipid profile after burn by characterizing key lipids as potential diagnostic and outcome indicators in critically injured patients.

Metabolomics and Precision Medicine in Trauma: The State of the Field

“…They found that elevated levels of saturated and mono-unsaturated FFA are correlated with increased mortality. In non-survivors, there were limited pro-inflammatory cytokines, despite high levels of saturated FFA, suggesting that these patients lacked the appropriate physiologic inflammatory response needed to react to the insult (101). Other markers of oxidative stress such as hypoxanthine, indoxyl sulfate, glucuronic acid, gluconic acid, proline, uracil, nitrotyrosine, uric acid, and trihydroxy cholanoic acid have been identified in rat models of burns suggesting potential for distinguishing between septic and non-septic burn patients (102).…”

Ringer’s Lactate Prevents Early Organ Failure by Providing Extracellular Calcium

“…The designs of our in vitro and in vivo studies build on previous clinical studies showing unsaturated NEFAs, such as linoleic acid, to be increased in critical illnesses [15][16][17][18][19], the sera [20,21], and pancreatic collections [22,24,35] of patients with severe AP. In vitro, we note an energetically favorable interaction between linoleic acid and calcium but not lactate.…”

“…Fatty acids are elevated during critical illnesses [15][16][17][18][19] such as severe acute pancreatitis in humans [20,21] and rodents [22][23][24][25], but not during mild disease [22,23]. Previous studies have shown hypocalcemia to result from fatty acid administration [26] and calcium to be present in the (peri) pancreatic fat necrosis associated with pancreatitis [24], consistent with saponification [24,27,28].…”

A prospective pilot study using metabolomics discloses specific fatty acid, catecholamine and tryptophan metabolic pathways as possible predictors for a negative outcome after severe trauma

“…Further, they are increased after bone fracture [47]. Further, non-trauma related intensive-care conditions such as burn or acute pancreatitis injuries also lead to increased concentrations of FFAs [48–50]. FFAs could trigger myocardial injury through TLR4 activation [51], and they have been directly related with cardiovascular mortality [52].…”