Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans

Abstract

Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance.

© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1

Representative Beckman Multisizer profiles for adipose cell size distribution are shown in two IS and two IR subjects at baseline (PRE) and at peak weight (POST). Nadir, indicated by open arrow, separates two populations of small cells, distributed as a double exponential tail to the left of nadir, and large cells, distributed as a Gaussian curve. The black arrow indicates peak diameter (center of Gaussian curve).

Figure 2

Measures of adipose cell size and distribution in IS and IR subjects at baseline (A) and changes with weight gain for peak diameter (B), nadir (C), and percentage of small cells (D). Mean ± SEM, analyzed via ANCOVA with adjustment for %BF (A) or paired Student t test (B, C, and D). Diam, diameter.

Figure 3

Change in insulin resistance, as measured by SSPG, as a function of ΔVAT, IHL (Lipid/H2O), and peak diameter of adipose cells in IS (left) and IR (right) humans. General linear regression with adjustment for Δ%BF. Standardized r and P values are reported.