1. Substrate movements in forearm muscle and subcutaneous adipose tissue were studied, by measurement of arteriovenous differences and blood flow, in seven normal subjects after an overnight fast and then for 6 h after ingestion of a mixed meal. Overall substrate balances were examined in terms of the flux of gram-atoms of carbon. 2. As found previously, the forearm was approximately in carbon balance (import equal to export) after the overnight fast, whereas adipose tissue was a net exporter of carbon, mainly in the form of non-esterified fatty acids. 3. After the meal, arterialized plasma concentrations of glucose and lactate rose sharply (peak at 60 min), whereas those of non-esterified fatty acids and glycerol fell (nadir at 60-120 min). Plasma triacylglycerol concentrations rose slowly to peak at 240 min;much of this rise was accounted for by a rise in the chylomicron fraction. 4. Both tissues took up glucose at an increased rate after the meal. Release of non-esterified fatty acids and glycerol from adipose tissue was suppressed. Clearance of triacylglycerol by both tissues increased after the meal, but was more marked in adipose tissue, where the fractional extraction of chylomicron-triacylglycerol reached 44% at 240 min. 5. The forearm rapidly became a considerable net importer of carbon, and remained so until 6 h after the meal when it was again in approximate carbon balance. Glucose uptake dominated the forearm carbon balance. Adipose tissue was a net importer of carbon from 30 min until 5 h after the meal and then reverted to net export. Clearance of triacylglycerol carbon made the largest contribution to this positive balance, but towards the end of the study this was increasingly counterbalanced by simultaneous non-esterified fatty acid release.

Epinephrine has effects on both blood flow and metabolism in adipose tissue. To investigate how these effects might interact in vivo, epinephrine was infused into six healthy volunteers at a rate of 25 ng.kg-1.min-1. The rates of action of lipoprotein lipase and hormone-sensitive lipase in adipose tissue were calculated by measurement of arteriovenous differences across subcutaneous abdominal adipose tissue, and adipose tissue blood flow was measured. Epinephrine caused a significant rise in adipose tissue blood flow (P < 0.001), and the net efflux of nonesterified fatty acids (NEFA) from adipose tissue increased significantly (P < 0.05). Most of this efflux could be accounted for by hormone-sensitive lipase-derived NEFA efflux from cells (P < 0.05), but there was also a significant rise in the contribution of lipoprotein lipase-derived NEFA (P < 0.05). We conclude that adipose tissue blood flow plays an important role in the regulation of lipid metabolism, controlling substrate presentation for lipoprotein lipase and also preventing the local accumulation of fatty acids derived from both hormone-sensitive lipase and lipoprotein lipase.

Aims/hypothesis Increased NEFA production and concentrations may underlie insulin resistance. We examined systemic and adipose tissue NEFA metabolism in insulinresistant overweight men (BMI 25-35 kg/m 2 ). Methods In a cohort study we examined NEFA concentrations in men in the upper quartile of fasting insulin (n=124) and in men with fasting insulin below the median (n = 159). In a metabolic study we examined NEFA metabolism in the fasting and postprandial states, in ten insulin-resistant men and ten controls. Results In the cohort study, fasting NEFA concentrations were not significantly different between the two groups (median values: insulin-resistant men, 410 µmol/l; controls, 445 µmol/l). However, triacylglycerol concentrations differed markedly (1.84 vs 1.18 mmol/l respectively, p<0.001). In the metabolic study, arterial NEFA concentrations again did not differ between groups, whereas triacylglycerol concentrations were significantly higher in insulin-resistant men. Systemic NEFA production and the release of NEFA from subcutaneous adipose tissue, expressed per unit of fat mass, were both reduced in insulin-resistant men compared with controls (fasting values by 32%, p=0.02, and 44%, p=0.04 respectively). 3-Hydroxybutyrate concentrations, an index of hepatic fat oxidation and ketogenesis, were lower (p=0.03). Conclusions/interpretation Adipose tissue NEFA output is not increased (per unit weight of tissue) in insulin resistance. On the contrary, it appears to be suppressed by high fasting insulin concentrations. Alterations in triacylglycerol metabolism are more marked than those in NEFA metabolism and are indicative of altered metabolic partitioning of fatty acids (decreased oxidation, increased esterification) in the liver.