Abstract 18671: The Response of Saturated Non-Esterified Fatty Acids to a Glucose Challenge is Distinct From Unsaturated, and Altered in Insulin Resistance
Introduction: Insulin suppresses intracellular lipolysis in adipocytes, and poor suppression of non-esterified fatty acid (NEFA) release is directly related to adipocyte insulin resistance (IR). It is not known whether the suppression is uniform for all fatty acids (FAs).
Objectives: We used a compartmental model of NEFA trafficking in response to a glucose challenge. Our objective was to 1) determine if trafficking of all FAs is uniform, and 2) determine whether it is altered in IR.
Methods: This was an ancillary study. Optimally healthy (n=15) and IR (n=60) subjects with HOMA scores of 0.65 [0.59, 0.88] and 3.21 [2.34, 4.36] respectively (p<0.0001 by χ2) were given a frequently sampled intravenous glucose tolerance test. Four subjects from each group were selected by stratifying IR. Six FAs were measured by GC-MS (myristic, palmitic, palmitoleic, stearic, oleic, and linoleic acids). Kinetic parameters representing the fractional rate of NEFA appearance (Ra), the rate of NEFA disappearance (kNEFA), threshold for glucose-induced suppression (tG), and IC50 for glucose inhibition of NEFA production (gIC50) were estimated. Differences are reported as mean [95% CI].
Results: Ra was highest for linoleate (10.6 [7.8,14.5]%/min/L) and lowest for stearate (2.7 [2.0, 3.7]%/min/L). Ra was 48 [24, 64] lower in IR (p=0.02) for all FAs except stearate, which was unchanged. Mean kNEFA (min-1) for the unsaturated FAs was 106% [50, 183] higher than for palmitate. In IR, only kNEFA for stearate was greater, by 55% [14, 76] (p=0.05). The tG (mM) was not different among FAs, however in IR it was 94% [46, 159] greater for all FAs (p<0.001). In healthy subjects, the gIC50 (mM) for stearate (0.59 [0.17, 2.09]) and palmitate (0.48 [0.14, 1.70]) were greater than for linoleate (0.10 [0.03, 0.34]) and palmitoleate (0.07 [0.02, 0.25]) (p<0.0001), however this difference was not present in IR.
Conclusions: In response to a glucose challenge, trafficking of individual FAs were not uniform. In particular, both saturated FAs had lower Ra and higher gIC50 in comparison to other FAs in both healthy and IR. In IR, all FAs except stearate had lower Ra. Furthermore, only stearate kNEFA was elevated with IR, indicating stearate trafficking may be a key marker of adipocyte dysfunction in IR.
Author Disclosures: R.E. Walker: None. J.L. Ford: None. M.H. Green: None. G.C. Shearer: None.
- © 2016 by American Heart Association, Inc.