Direct Free Fatty Acid Uptake Into Human Adipocytes In Vivo

Abstract

We sought to assess whether direct uptake of circulating free fatty acids (FFAs) by adipocytes occurs in vivo in overnight postabsorptive humans and, if so, whether there are regional differences in uptake between lean and obese women and men. We used bolus injections of radiolabeled FFA tracers followed by carefully timed adipose tissue biopsies. First, we validated a method to measure direct adipocyte FFA uptake and then quantitated this process using the modified methods in normalweight postabsorptive men and women. We then used a continuous infusion of radiolabeled FFA to measure direct and indirect (VLDL) regional adipose tissue uptake in obese men and women. Direct FFA uptake was greater in women than men: 8.2 ؎ 0.6 vs. 4.0 ؎ 0.5% (P < 0.0001) of FFAs were taken up by subcutaneous adipose tissue, respectively. Abdominal subcutaneous fat took up FFAs more avidly than femoral fat in men, but this did not occur in women. Similar sex and regional difference were found to occur in obese women and men. Gene expression of fatty acid transporters was greater in abdominal than femoral fat in men (P < 0.05) but not in women (P ‫؍‬ 0.80). We observed sex-and site-specific recycling of circulating FFAs into subcutaneous fat. This is a novel FFA disposal pathway that may also play a role in the development or maintenance of body fat distribution. Regional variations in facilitated fatty acid transport may contribute to this process. Diabetes 56:1369-1375, 2007

Plasma Free Fatty Acid Storage in Subcutaneous and Visceral Adipose Tissue in Postabsorptive Women

“…This is the same pattern present in normal-weight women (15) and contrasts with the greater abdominal than femoral SA in normal-weight men (15).…”

“…The relative storage of FFA via this direct pathway in upper versus lower body fat was consistent with sex-specific differences in body fat distribution, i.e., preferential upper body fat accumulation in men but not in women and greater total storage in subcutaneous fat of women. We estimated that this physiological process of FFA recycling independent of the VLDL-triglycerides/lipoprotein lipase (VLDL-TG/LPL) pathway might serve to redistribute fat from upper body stores to lower body stores in women but not men (15). Unfortunately, we had no information regarding the presence or absence of this process in visceral fat in humans.…”

“…Despite the rapid FFA outflow, ϳ8% of circulating FFA are directly stored back into subcutaneous adipose tissue in normalweight women (15). Although this pathway contributes a relatively small portion to total fat storage, it seems to favor fat redistribution to lower body fat specifically in women but not men (15).…”

“…Investigators failed to detect disappearance of circulating FFA across an adipose tissue bed in postabsorptive men using the combination of isotope dilution techniques and arteriovenous balance (12)(13)(14), although FFA disappearance across adipose tissue has been reported under postprandial or hyperinsulinemic conditions (12,14). Using an intravenous bolus of 14 Clabeled FFA and carefully timed subcutaneous adipose tissue biopsies to detect direct FFA storage, we estimated that ϳ3 and 8% of circulating FFA is incorporated into subcutaneous adipose lipid in normal-weight, postabsorptive men and women, respectively (15). Although a small fraction of FFA disposal, the pattern of storage was most interesting.…”

More insights into a human adipose tissue GPAT activity assay

“…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.…”