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Abdominal Obesity in Older Women: Potential Role for Disrupted Fatty Acid Reesterification in Insulin Resistance

The John B. Pierce Laboratory (C.W.Y., L.D.) and the Departments of Epidemiology & Public Health (C.W.Y., L.D.) and Internal Medicine (J.D.), Yale University School of Medicine, New Haven, Connecticut 06519

Address all correspondence and requests for reprints to: Loretta DiPietro, Ph.D., M.P.H., The John B. Pierce Laboratory, 290 Congress Avenue, New Haven, Connecticut 06519. E-mail: ldipietro{at}jbpierce.org.

Context: Excess abdominal adiposity is a primary factor for insulin resistance in older age.

Objectives: Our objectives were to examine the role of abdominal obesity on adipose tissue, hepatic, and peripheral insulin resistance in aging, and to examine impaired free fatty acid metabolism as a mechanism in these relations.

Design: This was a cross-sectional study.

Setting: The study was performed at a General Clinical Research Center.

Participants: Healthy, inactive older (>60 yr) women (n = 25) who were not on hormone replacement therapy or glucose-lowering medication were included in the study. Women with abdominal circumference values above the median (>97.5 cm) were considered abdominally obese.

Main Outcome Measures: Whole-body peripheral glucose utilization, adipose tissue lipolysis, and hepatic glucose production were measured using in vivo techniques according to a priori hypotheses.

Results: In the simple analysis, glucose utilization at the 40 mU insulin dose (6.3 ± 2.8 vs. 9.1 ± 3.4; P < 0.05), the index of the insulin resistance of basal hepatic glucose production (23.6 ± 13.0 vs. 15.1 ± 6.0; P < 0.05), and insulin-stimulated suppression of lipolysis (35 vs. 54%; P < 0.05) were significantly different between women with and without abdominal obesity, respectively. Using the glycerol appearance rate to free fatty acid ratio as an index of fatty acid reesterification revealed markedly blunted reesterification in the women with abdominal adiposity under all conditions: basal (0.95 ± 0.29 vs. 1.35 ± 0.47; P < 0.02); low- (2.58 ± 2.76 vs. 6.95 ± 5.56; P < 0.02); and high-dose (4.46 ± 3.70 vs. 12.22 ± 7.13; P < 0.01) hyperinsulinemia. Importantly, fatty acid reesterification was significantly (P < 0.01) associated with abdominal circumference and hepatic and peripheral insulin resistance, regardless of total body fat.

Conclusion: These findings support the premise of dysregulated fatty acid reesterification with abdominal obesity as a pathophysiological link to perturbed glucose metabolism across multiple tissues in aging.