Adipocyte development and insulin resistance

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Fat pads dynamically regulate energy storage capacity under energy excess and deficit. This remodeling process is not completely understood, with controversies regarding differences between fat depots and plasticity of adipose cell number. We previously examined changes of mouse adipose cell-size distributions in epididymal, inguinal, retroperitoneal, and mesenteric fat under both weight gain and loss. With mathematical modeling, we specifically analyzed the recruitment, growth/shrinkage, and loss of adipose cells, including the size dependence of these processes. We found a qualitatively universal adipose tissue remodeling process in all four fat depots: (1) There is continuous recruitment of new cells under weight gain; (2) The growth and shrinkage of larger cells (diameter > 50 microns) is proportional to cell surface area; and (3) Cell loss occurs under prolonged weight gain, with larger cells more susceptible. The mathematical model gives a predictive integrative picture of adipose tissue remodeling, and can be used to examine changes in the relative importance of these specific cellular processes in obesity and diabetes. Fat pads continuously recruited new adipose cells under weight gain. Growth/shrinkage of large adipose cells is proportional to their surface area. Larger adipose cells are more susceptible to cell loss under prolonged weight gain. In previous publications, we demonstrated that there appeared to be a periodicity in changes in the cell-size probability distributions by analyzing longitudinal data from two Zucker fatty rats. In that work, we proposed a mathematical model that could give rise to such periodicity, and a prediction of that model was that a high-fat diet may lead to a decrease in the period, relative to chow. Our collaborator (Mathilde Arroyo in Dr. Cushman's laboratory) carried out experiments in Zucker fatty rat, and we have been analyzing the resulting data to test our prediction. It appears that the variability in this new dataset may mask the appearance of any regularity of the form suggested by the prediction. This work is ongoing.