Storage of Circulating Free Fatty Acid in Adipose Tissue of Postabsorptive Humans

Abstract

OBJECTIVEPreferential upper-body fat gain, a typical male pattern, is associated with a greater cardiometabolic risk. Regional differences in lipolysis and meal fat storage cannot explain sex differences in body fat distribution. We examined the potential role of the novel free fatty acid (FFA) storage pathway in determining body fat distribution in postabsorptive humans and whether adipocyte lipogenic proteins (CD36, acyl-CoA synthetases, and diacylglycerol acyltransferase) predict differences in FFA storage.RESEARCH DESIGN AND METHODSRates of postabsorptive FFA (palmitate) storage into upper-body subcutaneous (UBSQ) and lower-body subcutaneous (LBSQ) fat were measured in 28 men and 53 premenopausal women. Stable and radiolabeled palmitate tracers were intravenously infused followed by subcutaneous fat biopsies. Body composition was assessed with a combination of dual-energy X-ray absorptiometry and computed tomography.RESULTSWomen had greater FFA (palmitate) storage than men in both UBSQ (0.37 ± 0.15 vs. 0.27 ± 0.18 μmol · kg−1 · min−1, P = 0.0001) and LBSQ (0.42 ± 0.19 vs. 0.22 ± 0.11 μmol · kg−1 · min−1, P < 0.0001) fat. Palmitate storage rates were significantly greater in LBSQ than UBSQ fat in women, whereas the opposite was true in men. Plasma palmitate concentration positively predicted palmitate storage in both depots and sexes. Adipocyte CD36 content predicted UBSQ palmitate storage and sex-predicted storage in LBSQ fat. Palmitate storage rates per kilogram fat did not decrease as a function of fat mass, whereas lipolysis did.CONCLUSIONSThe FFA storage pathway, which had remained undetected in postabsorptive humans until recently, can have considerable, long-term, and sex-specific effects on body fat distribution. It can also offer a way of protecting the body from excessive circulating FFA in obesity.

Sex and depot differences in ex vivo adipose tissue fatty acid storage and glycerol-3-phosphate acyltransferase activity

“…Although regional balances of fatty acids (uptake vs. release) should determine whether one depot expands at the expense of another, interindividual differences in regional lipolysis (8,13,24) and meal fat storage (21,26,31) do not appear to explain differences in body fat distribution. We found that direct free fatty acid (FFA) storage rates in subcutaneous fat are greater in women than men and that the sex-specific variations in direct FFA storage into adipocyte triacylglycerol (TAG) are consistent with body fat distribution patterns (16,18,28). On average, the protein content (CD36 and fatty acid transport protein 1) and enzyme activity [acylCoA synthetase (ACS) and diacylglycerol-acyltransferase (DGAT)] are greater in omental than subcutaneous adipose tissue depots (1).…”

More insights into a human adipose tissue GPAT activity assay

“…These results are consistent with our previous findings that women have greater palmitate storage into adipose tissue than men. 4 The development of a reliable GPAT enzyme activity assay has allowed us to define variations in GPAT activity among adipose tissue depots, sexes, and ranges of adipocyte size. Future investigation of GPAT and other fatty acid storage factor activity under varying metabolic states may prove useful in delineating differences in fat distribution and progression to metabolic disease states.…”

“…We also wanted to delineate if GPAT variations accounted for previously observed variations in adipose tissue fatty acid storage rates. 1,4,5,10 While GPAT is responsible for the first committed step of triacylglycerol (TAG) synthesis, diacylglycerol acetyl transferase (DGAT) is responsible for the final step of TAG synthesis: the conversion of diacylglycerols (DG) to TAG. 6 We have reported that DGAT activity correlates with rates of FFA storage in subcutaneous fat in some depots under some conditions.…”

Measuring plasma fatty acid oxidation with intravenous bolus injection of 3H- and 14C-fatty acid

“…Rapid intravenous injection of an FFA tracer is useful when aspects of nonoxidative FA metabolism are investigated. Examples include the incorporation of plasma FAs into VLDL-triglyceride (TG) ( 15,16 ) or the storage/uptake of plasma FAs into tissues (17)(18)(19)(20). In addition, intravenous injections can be more convenient than a continuous infusion, because bolus injections obviate the need to keep the volunteers connected to an infusion pump, thus offering greater mobility and freedom during experimental days.…”

“…The data were collected as part of a larger study examining the oxidative and the nonoxidative disposal of plasma FFAs in humans. Data related to the nonoxidative aspect of the study have been published elsewhere ( 17,18 ).…”