Storage of circulating free fatty acid in adipose tissue of postabsorptive humans: quantitative measures and implications for body fat distribution

Abstract

Objective: Preferential 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 methods: Rates 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.

Results: Women 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.

Conclusions: The 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.

FIG. 1.

Relationship between palmitate storage in UBSQ fat (μmol/kg fat/min) and plasma palmitate (Palm) concentration (μmol/L) (A) and palmitate storage in LBSQ fat (μmol/kg fat/min) and plasma palmitate concentration (μmol/L) (B).

FIG. 2.

Relationship between abdominal CD36 content (units per mg lipid) (A), abdominal ACS activity (pmol/mg lipid/min) (B), abdominal DGAT activity (pmol/mg lipid/min) (C), and UBSQ fat mass and between femoral CD36 content (units per mg lipid) (D), femoral ACS activity (pmol/mg lipid/min) (E), femoral DGAT activity (pmol/mg lipid/min) (F), and LBSQ fat mass in men (●, solid line) and women (○, dashed line).

FIG. 3.

Relationship between palmitate (Palm) storage in UBSQ fat (μmol/1,000 adipocytes/min) and abdominal CD36 content (units per 1,000 adipocytes) (A), abdominal ACS activity (pmol/1,000 adipocytes/min) (B), and abdominal DGAT activity (pmol/1,000 adipocytes/min) (C) and between palmitate storage in LBSQ fat (μmol/1,000 adipocytes/min) and femoral CD36 content (units per 1,000 adipocytes) (D), femoral ACS activity (pmol/1,000 adipocytes/min) (E), and femoral DGAT activity (pmol/1,000 adipocytes/min) (F) in men (●, solid line) and women (○, dashed line). Log values were used to achieve normal distribution.

FIG. 4.

Palmitate release rate into whole-body subcutaneous fat (μmol/kg fat/min) versus subcutaneous fat mass (kilograms) (A) and palmitate storage rates into whole-body subcutaneous fat (μmol/kg fat/min) versus subcutaneous fat mass (kilograms) (B).