Waves of adipose tissue growth in the genetically obese Zucker fatty rat

Abstract

Background: In mammals, calories ingested in excess of those used are stored primarily as fat in adipose tissue; consistent ingestion of excess calories requires an enlargement of the adipose tissue mass. Thus, a dysfunction in adipose tissue growth may be a key factor in insulin resistance due to imbalanced fat storage and disrupted insulin action. Adipose tissue growth requires the recruitment and then the development of adipose precursor cells, but little is known about these processes in vivo.

Methodology: In this study, adipose cell-size probability distributions were measured in two Zucker fa/fa rats over a period of 151 and 163 days, from four weeks of age, using micro-biopsies to obtain subcutaneous (inguinal) fat tissue from the animals. These longitudinal probability distributions were analyzed to assess the probability of periodic phenomena.

Conclusions: Adipose tissue growth in this strain of rat exhibits a striking temporal periodicity of approximately days. A simple model is proposed for the periodicity, with PPAR signaling driven by a deficit in lipid uptake capacity leading to the periodic recruitment of new adipocytes. This model predicts that the observed period will be diet-dependent.

Figure 1. Cell-size data for rat 1, day 6.

Figure 2. Cell-size data for rat 2, day 13.

Figure 3. Fractional differences of adipose cell-size probability distributions (day - mean)/mean as a function of cell diameter.

Figure 4. Heat-map showing data and gaps in data over the entire time-course for rat 1.

The axis corresponds to cell diameter (m, increasing towards negative ) and the axis corresponds to time (days).

Figure 5. Log-likelihood of models for rat 1.

Figure 6. Log-likelihood of models for rat 2.

Figure 7. Probability of period as a function of period, marginalizing over all models (period-bin-size, bin number, phase) in 5-day intervals.

Figure 8. Cell-size probability distributions in each period-bin (from 0 through 4) for rat 1 for the most likely model, 5 bins of 11 days each.

Figure 9. Cell-size probability distributions in each period-bin (from 0 through 6) for rat 2 for the most likely model, 7 bins of 8 days each.

Figure 10. Periodic small adipocyte recruitment predicted by a simple model of adipocyte proliferation driven by lipid flux vs. lipid uptake capacity.

The period is longer for lower lipid flux, .