Background:

Although obesity is commonly linked with metabolic disease risk, some obese adults do not develop metabolic abnormalities, such as insulin resistance.

Objectives:

The primary aim of this study was to determine whether alterations in fatty acid mobilization and uptake underlie differences in insulin sensitivity (S i) among a seemingly homogeneous cohort of obese women.

Methods:

Insulin sensitivity (frequently sampled intravenous glucose tolerance test), basal fatty acid rate of disappearance from plasma (Rd), resting whole-body fat oxidation, intramyocellular triacylglycerol (IMTG) concentration and markers of skeletal muscle inflammation were measured in 21 obese women. Participants were divided into tertiles based on their S i. The subset of participants with the lowest S i (LOW-S i; S i⩽ 2.1 (mU/l)− 1 min− 1; n= 7) was compared with the subset of participants with the highest S i, who exhibited relatively normal insulin sensitivity (NORM-S i; S i⩾ 3.4 (mU/l)− 1 min− 1; n= 8).

Results:

Despite nearly identical physical characteristics in LOW-S i vs NORM-S i (body mass index: 34±2 vs 34±1 kg m− 2;% body fat: 48±1 vs 47±1%; waist circumference: 104±2 vs 104±2 cm; VO 2 max: 2.2±0.2 vs 2.3±0.1 l min− 1), fatty acid Rd was nearly 30% lower in NORM (P= 0.02). Importantly, the greater rate of fatty acid uptake in LOW-S i vs NORM-S i did not translate to higher rate of fat oxidation (3.5±0.2 vs 3.7±0.2 μmol kg− 1 min− 1) or to a measureable difference in IMTG content (68.3±12.7 vs 63.7±6.7 μmol g− 1 dry weight). In conjunction with the lower fatty acid Rd in NORM-S i vs LOW-S i, activation of inflammatory pathways known to impair insulin action in skeletal muscle was also lower (lower phosphorylated c-jun N-terminal kinase (JNK) and higher inhibitor of κB (IκB-α) abundance). In contrast, LOW-S i and NORM-S i exhibited no differences in plasma markers of inflammation (TNFα, IL-6 (interleukin-6), MCP-1).

Conclusion:

These findings suggest that obese women who maintain a relatively low rate of endogenous fatty acid uptake may be somewhat ‘protected’against the development of insulin resistance potentially by less activation of inflammatory pathways within skeletal muscle.