Patterson, Bruce W.

We measured the incorporation of systemic free fatty acids (FFA) into circulating very low-density lipoprotein triglycerides (VLDL-TGs) under postabsorptive, postprandial, and walking conditions in humans. Fifty-five men and 85 premenopausal women with BMI 18–24 (lean) and 27–36 kg/m2 (overweight/obese) received an intravenous bolus injection of [1,1,2,3,3-2H5]glycerol (to measure VLDL-TG kinetics) and either [1-14C]palmitate or [9,10-3H]palmitate to determine the proportion of systemic FFA that is converted to VLDL-TG. Experiments started at 0630 h after a 12-h overnight fast. In the postabsorptive protocol, participants rested and remained fasted until 1330 h. In the postprandial protocol, volunteers ingested frequent portions of a fat-free smoothie. In the walking protocol, participants walked on a treadmill for 5.5 h at ∼3× resting energy expenditure. Approximately 7% of circulating FFA was converted into VLDL-TG. VLDL-TG secretion rates (SRs) were not statistically different among protocols. Visceral fat mass was the only independent predictor of VLDL-TG secretion, explaining 33–57% of the variance. The small proportion of systemic FFA that is converted to VLDL-TG can confound the expected relationship between plasma FFA concentration and VLDL-TG SRs. Regulation of VLDL-TG secretion is complex in that, despite a broad spectrum of physiological FFA concentrations, VLDL-TG SRs did not vary based on different acute substrate availability.

OBJECTIVE— We assessed the direct (VLDL-triglycerides [VLDL-TG] independent) storage of circulating free fatty acids (FFAs) in visceral and subcutaneous fat in postabsorptive women. RESEARCH DESIGN AND METHODS— Twelve women (BMI 29.6 ± 6.6 kg/m2) received an identical, intravenous bolus dose of [1-14C]oleate followed by timed subcutaneous fat biopsies (abdominal and femoral) and then omental fat biopsy during tubal ligation surgery. Regional fat masses were assessed by combining dual-energy X-ray absorptiometry and computed tomography scanning. Separately, we assessed the fraction of FFA tracer entering VLDL-TG over the time representing the delay in collecting omental fat. RESULTS— Site-specific fat specific activity (SA) (dpm/g lipid) decreased as a function of fat mass in both upper-body subcutaneous (UBSQ) and visceral fat depots. These patterns are consistent with dilution of a relatively fixed amount of FFA tracer within progressively greater amounts of fat. Interestingly, femoral SA did not vary as a function of lower-body subcutaneous (LBSQ) fat mass. [1-14C]oleate storage per million LBSQ adipocytes was positively associated with LBSQ fat mass, but no significant relationships were observed in UBSQ or visceral fat depot. The fraction of [1-14C]oleate stored in UBSQ, LBSQ, and visceral fat was 6.7 ± 3.2, 4.9 ± 3.4, and 1.0 ± 0.3%, respectively. Only ∼4% of the tracer traversed VLDL-TG over 9.5 h. CONCLUSIONS— The increase in FFA tracer storage per adipocyte as a function of LBSQ fat mass implies that LBSQ adipocytes, in contrast to UBSQ and omental adipocytes, store more FFA in women with greater adiposity. The direct FFA storage pathway might play a role in favoring lower-body fat accumulation in women.

Lipolysis of adipose tissue triglycerides releases glycerol. Twenty-four volunteers, of whom 6 were obese and 13 were women, received a primed-constant infusion of 2H5-glycerol for 120 min during postabsorptive steady-state conditions. Arterial, abdominal venous, and interstitial (microdialysis) samples were taken, and a four-compartment model was applied to assess subcutaneous abdominal adipose tissue glycerol kinetics. Adipose tissue blood flow was measured using 133Xe washout. Venous glycerol concentrations (median 230 μmol/l [interquartile range 210–268]) were consistently greater than those of arterial blood (69.1 μmol/l [56.5–85.5]), while glycerol isotopic enrichments (tracer-to-tracee ratio) were greater in arterial blood (8.34% [7.44–10.1]) than venous blood (2.34% [1.71–2.69], P < 0.01). Microdialysate glycerol enrichment was 1.44% (1.11–1.79), indicating incomplete permeability of glycerol between capillary blood and interstitium. Calculated interstitial glycerol concentrations were between 270 μmol/l (256–350) and 332 μmol/l (281–371) (examining different boundary conditions). The calculated capillary diffusion capacity (ps) was between 2.21 ml · 100 g tissue−1 · min−1 (1.31–3.13) and 3.09 ml · 100 g tissue−1 · min−1 (1.52–4.90) and correlated inversely with adiposity (Rs ≤ −0.45, P < 0.05). Our results support previous estimates of interstitial glycerol concentration within adipose tissue and reveal capillary diffusion capacity is reduced in obesity.