Metabolism of triacetin-derived acetate in dogs

Abstract

Triacetin is a water-soluble triglyceride that may have a role as a parenteral nutrient. In the present study triacetin was administered intravenously to mongrel dogs (n = 10) 2 wk after surgical placement of blood-sampling catheters in the aorta and in the portal, hepatic, renal, and femoral veins. [1-14C]Acetate was infused to allow quantification of organ uptake of acetate as well as systemic turnover and oxidation. Systemic acetate turnover accounted for approximately 70% of triacetin-derived acetate, assuming complete hydrolysis of the triglyceride. Approximately 80% of systemic acetate uptake was rapidly oxidized. Significant acetate uptake was demonstrated in all tissues (liver, 559 +/- 68; intestine, 342 +/- 23; hindlimb, 89 +/- 7; and kidney, 330 +/- 37 mumol/min). In conclusion, during intravenous administration in dogs, the majority of infused triacetin undergoes intravascular hydrolysis, and the majority of the resulting acetate is oxidized. Thus, energy in the form of short-chain fatty acids can be delivered to a resting gut via intravenous infusion of a short-chain triglyceride.

Changes in Intermediary Metabolism in Severe Surgical Illness

“…It is in fact possible that the only beneficial aspect of nonprotein calories in this circumstance is the role of exogenous glucose in stimulating insulin release, which itself has a pronounced anabolic effect, particularly in conjunction with an exogenous supply of ample amino acids [44]. Alternative substrates, such as medium-chain fatty acids [47], dicarboxylic acids [48,49], and triacetin [50], might prove useful because they circumvent the need for CPT-I, thereby being efficiently oxidized. Because there is little evidence that critically ill patients have diminished ability to oxidize the substrates already available, it is unclear if these "alternative" substrates provide a unique advantage.…”

Effect of Co-Solvents on the Controlled Release of Calcitonin Polypeptide fromIn SituBiodegradable Polymer Implants

“…Most technology for developing polymer drug delivery systems use organic solvents such as acetone, ethyl acetate, dichloromethane, dioxane, hexane, tetrahydrofuran, propylene glycol, and 2-pyrrolidone (Matschke et al 2002). Specifically, for implants formed in situ, a broad range of solvents have been investigated including N-methyl-2-pyrrolidone (NMP) (Dunn et al 1994), dimethyl sulfoxide (DMSO), triacetin, benzyl benzoate, glycofurol and glycerol formal (Bleiberg et al 1993;Graham, Brudbeck, and McHush 1999;Chern and Zingermann 1999). Of these, the most preferred solvents are NMP and DMSO because of their pharmaceutical precedence (Dunn et al 1997).…”

Dietary triacetin, but not medium chain triacylglycerides, blunts weight gain in diet‐induced rat model of obesity

“…However, the mechanisms by which acetate impacts lipid metabolism are conflicting, either by inhibiting lipolysis (Ge et al, 2008; Hong et al, 2005), reducing fat accumulation through changes in fatty acid oxidation (Kondo, Kishi, Fushimi, & Kaga, 2009), reducing fatty acid synthesis (Yamashita et al, 2009), and/or reducing appetite (Frost et al, 2014). Triacetin infusion in female mongrel dogs showed that triacetin is hydrolysed intravascularly and primarily oxidized in the liver (Bleiberg et al, 1993). Additionally, triacetin‐derived acetate is rapidly taken up by the liver, hindlimb and intestine, suggesting that a small amount of acetate would be taken up by the adipose tissue (Bleiberg et al, 1993).…”

“…Triacetin infusion in female mongrel dogs showed that triacetin is hydrolysed intravascularly and primarily oxidized in the liver (Bleiberg et al, 1993). Additionally, triacetin-derived acetate is rapidly taken up by the liver, hindlimb and intestine, suggesting that a small amount of acetate would be taken up by the adipose tissue (Bleiberg et al, 1993). Finally, triacetin infusion in dogs led to decreased blood glucose levels and increased ketone bodies and free fatty acids (Bailey et al, 1991).…”