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Direct Free Fatty Acid Uptake Into Human Adipocytes In Vivo

Relation to Body Fat Distribution

From the Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota

Address correspondence and reprint requests to Michael D. Jensen, MD, Endocrine Research Unit, Mayo Clinic, 200 1st St. SW, Rm. 5-194 Joseph, Rochester, MN 55905. E-mail: jensen.michael{at}mayo.edu

Abbreviations: DEXA, dual-energy X-ray absorptiometry; FFA, free fatty acid; GCRC, General Clinical Research Center; HOMA-IR, homeostasis model assessment of insulin resistance; HPLC, high-performance liquid chromatography; LPL, lipoprotein lipase; TLC, thin-layer chromatography

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 normal-weight 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.

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