PET imaging reveals distinctive roles for different regional adipose tissue depots in systemic glucose metabolism in nonobese humans

Abstract

Excess amounts of abdominal subcutaneous (SAT) and visceral (VAT) adipose tissue (AT) are associated with insulin resistance, even in normal-weight subjects. In contrast, gluteal-femoral AT (GFAT) is hypothesized to offer protection against insulin resistance. Dynamic PET imaging studies were undertaken to examine the contributions of both metabolic activity and size (volume) of these depots in systemic glucose metabolism. Nonobese, healthy volunteers (n = 15) underwent dynamic PET imaging uptake of [¹⁸F]FDG at a steady-state (20 mU·m⁻²·min⁻¹) insulin infusion. PET images of tissue [¹⁸F]FDG activity were coregistered with MRI to derive K values for insulin-stimulated rates of fractional glucose uptake within tissue. Adipose tissue volume was calculated from DEXA and MRI. VAT had significantly higher rates of fractional glucose uptake per volume than SAT (P < 0.05) or GFAT (P < 0.01). K(GFAT) correlated positively (r = 0.67, P < 0.01) with systemic insulin sensitivity [glucose disappearance rate (R(d))] and negatively with insulin-suppressed FFA (r = -0.71, P < 0.01). SAT (r = -0.70, P < 0.01) and VAT mass (r = -0.55, P < 0.05) correlated negatively with R(d), but GFAT mass did not. We conclude that rates of fractional glucose uptake within GFAT and VAT are significantly and positively associated with systemic insulin sensitivity in nonobese subjects. Furthermore, whereas SAT and VAT amounts are confirmed to relate to systemic insulin resistance, GFAT amount is not associated with insulin resistance. These dynamic PET imaging studies indicate that both quantity and quality of specific AT depots have distinct roles in systemic insulin resistance and may help explain the metabolically obese but normal-weight phenotype.

Fig. 1.

Study design schematic. Shaded black boxes represent active dynamic positron emission tomography (PET) imaging after injection of [¹⁸F]FDG (fluorodeoxyglucose) radioactive tracer.

Fig. 2.

Representative PET and MRI. Imaging with region of interest (ROI) placement. An example illustrating MRI and dynamic PET imaging after injection of [¹⁸F]FDG. Top pictures represent abdominal imaging, and bottom pictures represent thigh imaging, with MR images on the left and PET images on the right. After MR-PET coregistration, ROI (shown as red ovals) were generated on the MR image and applied to the corresponding coregistered PET image (shown as white ovals) to generate regional FDG time activity curves. GFAT, gluteal-femoral adipose tissue.

Fig. 3.

Adipose tissue depot K values. FDG uptake in GFAT was similar to subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) differed significantly from both GFAT (*P < 0.01) and SAT (**P < 0.05), as shown above.

Fig. 4.

Systemic insulin sensitivity correlations. ◆, Men; ◇, women. A: positive significance between the glucose rate of disappearance (R_d) and the overall activity (K) of GFAT. B: no significance between the overall activity of SAT and R_d. C: significance between the activity of VAT and R_d. D: no significance between the amount of GFAT and insulin sensitivity. E: negative correlation between SAT volume and insulin sensitivity. F: a negative correlation between VAT volume and insulin sensitivity.