Abstract Body: Introduction: Two primary sources of long chain fatty acids fuel cardiac metabolism, albumin (ALB)-bound non-esterified fatty acids and triglycerides (TG) within lipoproteins, such as chylomicrons (CHY). Potential distinctions in metabolic fates of CHY-TG and ALB-fat are unexplored in in situ cardiomyocytes.

Hypothesis: Tracking metabolism of ¹³C enriched lipoprotein fat versus ALB-fat will elucidate distinct metabolic fates in functioning hearts.

Methods: ¹³C oleate CHY-TG were generated by rats as bioreactors, with duodenal infusion of ¹³C oleate micelles and collection of lymph containing 42% enriched ¹³C CHY-TG from the thoracic duct. Additional unlabeled fats in ¹³C CHY-TG were primarily palmitate/oleate/linoleate at 9.1%, 13.0% and 22.7%, respectively. Mouse (C57BL/6J) hearts were perfused with KH buffer containing glucose, lactate, and either ¹³C CHY-TG (n=6) or matched enrichment of ¹³C ALB-oleate with comparable unlabeled fats (n=5) and fatty acyl content (0.4 mM) as in ¹³C CHY-TG. Fat oxidation in the TCA cycle was determined by NMR of ¹³C glutamate enrichment and storage into TG by LC/MS.

Results: With 42% ¹³C enriched fats in both sources, ¹³C ALB-oleate provided 28 ± 3% of substrate into the TCA cycle versus 10 ± 1% from ¹³C CHY-TG (p = 0.002, Fig 1A) at similar rate pressure products. ¹³C ALB-oleate supported more ¹³C TG synthesis than ¹³C CHY-TG despite similar total TG content (Fig. 1B-D), suggesting greater TG turnover with ALB-fat. Thus, ALB-bound fat is selectively metabolized over CHY-TG with greater oxidation and storage.

Conclusion: Fatty acids in lipoprotein and ALB bound are not metabolically equivalent. ALB-fats are more efficiently routed to β-oxidation and TG synthesis than CHY-TG fats, showing greater metabolic accessibility within cardiomyocytes. The data are the first evidence of a distinct preference for oxidation and storage of albumin bound long chain fats versus those in chylomicron bound TG in functioning hearts and bear relevance to shifts in cardiac fat use in physiological and pathologic states.