Resistance to the antilipolytic effect of insulin in adipocytes of African-American compared to Caucasian postmenopausal women

Susan K Fried,Thomas Tittelbach,Jacob Blumenthal,Urmila Sreenivasan,Linda Robey,Jamie Yi,Sumbul Khan,Courtney Hollender,Alice S Ryan,Andrew P Goldberg

doi:10.1194/jlr.p000935

Susan K Fried, Thomas Tittelbach + Show 8 more

Open Access

https://doi.org/10.1194/jlr.p000935

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Abstract

High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant. We assessed possible depot and race difference in the antilipolytic effect of insulin in adipocytes isolated from abdominal (Abd) and gluteal (Glt) subcutaneous (sc) adipose tissue of overweight, postmenopausal AA and Caucasian (C) women. Percent body fat, fasting insulin, visceral adiposity, and adipocyte size was higher in AA women. Disinhibited lipolysis (presence of adenosine deaminase) per unit adipocyte surface area was similar in Abd and Glt and in AA and C. However, rates of 'basal' [submaximal phenylisopropyl adenosine (PIA)-suppressed] and insulin-suppressed lipolysis were higher in Abd of AA compared with C women even after adjustment for percent fat and visceral fat area. The race difference in rates of PIA- and insulin-suppressed lipolysis in AA were correlated with their hyperinsulinemia, but AA race, independent of fasting insulin, was associated with lower responsiveness (percent suppression) to submaximal insulin concentrations, although sensitivity (ED50) was not affected. Overall, these data are consistent with the hypothesis that decreased responsiveness of Abd adipocytes to antilipolytic effectors may contribute to higher FA availability and thereby to racial differences in insulin resistance.

Highlights

High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant
Visceral fat area was similar in C and AA women, but Abd sc fat area was higher in the AA so that the ratio of visceral adipose tissue (VAT) to sc adipose tissue (SAT) areas at L2-3 was lower in AA than in C women, with a similar trend at L4-5 (P = 0.1)
The current study demonstrated higher rates of insulinsuppressed lipolysis, as measured by glycerol or FA release in Abd sc adipocytes, of overweight postmenopausal AA than C women

Summary

Introduction

High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant. Rates of ‘basal’ [submaximal phenylisopropyl adenosine (PIA)suppressed] and insulin-suppressed lipolysis were higher in Abd of AA compared with C women even after adjustment for percent fat and visceral fat area. The race difference in rates of PIA- and insulin-suppressed lipolysis in AA were correlated with their hyperinsulinemia, but AA race, independent of fasting insulin, was associated with lower responsiveness (percent suppression) to submaximal insulin concentrations, sensitivity (ED50) was not affected. Overall, these data are consistent with the hypothesis that decreased responsiveness of Abd adipocytes to antilipolytic effectors may contribute to higher FA availability and thereby to racial differences in insulin resistance.—Fried, S.

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