Little is known about the fate of the lipolytic products produced by the action of lipoprotein lipase (LPL) on circulating triglyceride-rich lipoproteins in humans. We studied eight lean, healthy male subjects after an overnight fast. Subjects received infusions of lipid emulsions containing triolein labeled with 3 H on both the glycerol backbone and the fatty acid portion of the molecule; 14 C glycerol and 14 C oleate were coinfused to quantify the systemic and forearm release of 3 H glycerol and 3 H oleate resulting from LPL action. There was significant forearm uptake of both whole plasma triglyceride (presumed to represent primarily VLDL; extraction fraction 2.6 ؎ 0.6%, P < 0.005 vs. zero) and radiolabeled triglyceride derived from the lipid emulsion (a surrogate for chylomicrons; extraction fraction 31 ؎ 4%, P < 0.005 vs zero). Systemic clearance and forearm fractional extraction of glycerol was greater than that of oleate (P < 0.001 and P < 0.02, respectively). The systemic and forearm fractional release of LPL-generated glycerol were similar at 51 ؎ 4 and 59 ؎ 1%, respectively (NS). In contrast, the forearm fractional release of LPL-generated oleate was less than systemic fractional release (14 ؎ 2 vs. 36 ؎ 4%, P < 0.0001). These results indicate that there is escape, or spillover, of the lipolytic products of LPL action on triglyceride-rich lipoproteins in humans. They further suggest that LPL-mediated fatty acid uptake is an inefficient process, but may be more efficient in muscle than in adipose tissue. Diabetes 53:521-527, 2004 A lthough it is generally accepted that the action of hormone-sensitive lipase (HSL) in adipocytes is the primary source of plasma free fatty acids (FFAs) in normal postabsorptive individuals (1), the ubiquitous presence of lipoprotein lipase (LPL) (2) represents a potential additional source of plasma FFAs. Available evidence suggests that VLDL triglyceride is not an important source of plasma FFAs. Wolfe et al. (3) administered biosynthetic labeled VLDL to dogs and found that Ͼ95% of VLDL-triglyceride fatty acids were taken up directly into tissues without traversing the plasma FFA pool; in contrast, glycerol produced by the action of LPL on VLDL triglyceride was quantitatively released into the circulation.Chylomicrons, on the other hand, appear to be a significant source of FFAs during meal absorption. However, the magnitude of the chylomicron contribution to total FFA flux is controversial. Olivecrona et al. (4) gave chylomicrons labeled with 14 C glycerol and 3 H palmitate to rats, and found that ϳ90% of the administered 3 H was recovered in adipose tissue, whereas only trace amounts of 14 C could be found in adipose tissue. Recently, studies in which both chylomicrons and lipid emulsions containing labeled oleate were administered to mice found that 80 -90% of the label was recovered in plasma (5). Roust and Jensen (6) gave a meal containing radiolabeled triglyceride to human subjects and found that approximately one-third of dietary fatty acids were released into the sy...

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