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Title: Anesthesia and bariatric surgery gut preparation alter plasma acylcarnitines reflective of mitochondrial fat and branched-chain amino acid oxidation

item BHATTACHARYYA, SUDEEPA - Arkansas Children'S Nutrition Research Center (ACNC)
item ALI, MOHAMED - University Of California
item SMITH, WILLIAM - University Of California
item MINKLER, PAUL - Case Western Reserve University (CWRU)
item STOLL, MARIA - Case Western Reserve University (CWRU)
item HOPPEL, CHARLES - Case Western Reserve University (CWRU)
item Ferruzzi, Mario

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/14/2017
Publication Date: 8/22/2017
Citation: Bhattacharyya, S., Ali, M., Smith, W.H., Minkler, P.E., Stoll, M.S., Hoppel, C.L., Adams, S.H. 2017. Anesthesia and bariatric surgery gut preparation alter plasma acylcarnitines reflective of mitochondrial fat and branched-chain amino acid oxidation. American Journal of Physiology - Endocrinology and Metabolism. doi:10.1152/ajpendo.00222.2017.

Interpretive Summary: It is now accepted that the naturally-occurring bacteria and other microbes that reside in the gut play a critical role in health and physiology, in children and adults. The "gut microbiome" is readily altered by changes in diet, environment, and even aspects such as physical activity and a person's metabolic status. To better understand how the microbiome interacts with our bodies, it is critical to identify the molecules ("xenometabolites") and factors produced and modified by gut bacteria. Studying unique systems in which the microbiome is dramatically altered offers an opportunity to see how specific metabolites and xenometabolites track these alterations. Since the lead-in period to bariatric surgery involves procedures that remove a great deal of bacterial mass and gut contents, this time period was leveraged to determine blood patterns of specific metabolites called acylcarnitines in 17 obese women; these metabolites change when tissue fuels are broken down (amino acids, fats), but several also are derived from bacterial origins. The results revealed that pre-surgery blood acylcarnitines were consistent with a fasting-like fat oxidation, consistent with subjects being in negative energy balance. One xenometabolite derived from a bacterial fatty acid was elevated alongside endogenous, human markers of fat metabolism. This finding points to an interesting system in which bacteria-produced fat is stored in the body, and released and metabolized upon a fasting-like condition in which fatty acids are mobilized. The studies also revealed novel, unexpected effects of surgery itself (anesthesia) on reducing fat metabolism. The specific roles of bacterial xenometabolites in regulating metabolism and health remain to be fully elaborated, and will require additional identification of these factors under conditions in which the gut microbiome is shifted in parallel with host health and host physiology.

Technical Abstract: The period around bariatric surgery offers a unique opportunity to characterize metabolism responds to dynamic shifts in energy, gut function, and anesthesia. We analyzed plasma acylcarnitines in obese women (n=17) sampled in the overnight fasted/postabsorptive state ca. 1-2 weeks prior to surgery (Condition A), the morning of surgery (prior restriction to a 48 hr. clear liquid diet coupled in some cases a standard polyethylene glycol gut evacuation (Condition B), and following induction of anesthesia (Condition C). Comparisons tested if (a) plasma acylcarnitine derivatives reflective of fatty acid oxidation (FAO) and xenometabolism would be significantly increased and decreased, respectively, by pre-operative gut preparation/negative energy balance (Condition A vs. B), and (b) that anesthesia would acutely depress markers of FAO. Acylcarnitines associated with fat mobilization and FAO were significantly increased in Condition B: long-chain acylcarnitines (i.e., C18:1, ~70%), metabolites from active but incomplete FAO (i.e., C14:1 [161%], C14:2 [102%]) and medium- to short-chain acylcarnitines (i.e., C2 [91%], R-3-hydroxybutyryl- [245%], C6 [45%], cis-3,4-methylene-heptanoyl- [17%], etc.). Branched-chain amino acid markers displayed disparate patterns (i.e. isobutyryl- [40% decreased] vs. isovaleryl-carnitine [51% increased]). Anesthesia reduced virtually every acylcarnitine. These results are consistent with a fasting-type metabolic phenotype coincident with the pre-surgical "gut preparation" phase of bariatric surgery, and a major and rapid alteration of both fat and amino acid metabolism with onset of anesthesia. Whether or not pre-surgical or anesthesia-associated metabolic shifts in carnitine and fuel metabolism impact patient outcomes or surgical risks remain to be evaluated experimentally.