NEFA Dynamics in Adults With Severe Obesity and Insulin Resistance: No Coupling to the rs9939609 Risk Allele.

CONTEXT

The gene is highly expressed in adipose tissues; however, whether nonesterified fatty acids (NEFA) dynamics are impacted by has not been rigorously tested for in a uniformly obese study population comprising both sexes.

OBJECTIVE

To test for associations of the rs9939609 risk allele with NEFA suppression.

METHODS

We investigated 97 subjects with severe obesity but without diabetes, having genotype TT (n = 32), AT (n = 31), or AA (n = 34) in a cross-sectional observation study. NEFA suppression was assessed from a low-dose hyperinsulinemic euglycemic clamp with glucose-tracer as well as from the response to a standardized meal. Insulin sensitivity was assessed by hepatic and total insulin sensitivity measurements in the clamp and by the Matsuda index during the meal. Variables of possible importance for NEFA dynamics were primarily assessed by linear regression.

RESULTS

No genotype associations with fasting or suppressed NEFA were found, whether in the clamp or meal situation ( > .7 for all comparisons). Independent of genotype, higher fasting concentrations of NEFA and larger NEFA suppression were found in female compared with male subjects. Fasting NEFA or degree of suppression were not associated with total fat mass or body mass index. The respiratory quotient was negatively associated with NEFA suppression.

CONCLUSION

In a gender-mixed adult population of obese individuals, an obesity-risk allele did not affect fasting NEFA nor suppression thereof. These negative results on NEFA dynamics appear strengthened by the documentation of gender influence and associations with parameters reflective of insulin resistance.