Abdominal obesity in older women: potential role for disrupted fatty acid reesterification in insulin resistance

Abstract

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.

Figure 1

Insulin-stimulated suppression of FFAs by the level of abdominal circumference during the euglycemic-hyperinsulinemic clamp. *, Between-group differences P < 0.05; and **, P < 0.01 based on the t test for independent samples.

Figure 2

Individual changes in the Ra_glyc/FFA index under basal and insulin-stimulated conditions by level of abdominal adiposity. The ratio of Ra glycerol (mg·min⁻¹) adjusted for total fat mass (kg) over FFA (μmol·liter⁻¹) concentration. To convert to Systeme International units (μmol), multiply glycerol values by 10.86.

Figure 3

The association between total fat mass and hepatic insulin resistance under basal (A) and low insulin (B) stimulation, between fat mass and peripheral insulin sensitivity (C), and between fat mass and adipose tissue reesterification (D), all by level of abdominal adiposity. Solid circles and lines indicate an abdominal circumference less than or equal to 97.5 cm. Open circles and dashed lines represent an abdominal circumference more than 97.5 cm. IR_GP is under basal conditions. HGP is at the low insulin dose. The ratio of Ra glycerol (mg·min⁻¹) adjusted for total fat mass (kg) over FFA (μmol·liter⁻¹) concentration. To convert to Systeme International units, multiply glucose values by 5.5 or glycerol values by 10.86. M_40mU, Glucose utilization rate under higher insulin stimulation; ns, not significant.