Our hypothesis is that cell-size dependent cell death is an important component of adipose tissue remodeling under changing diet conditions. In mammals, fat must be either utilized or stored. Thus, we hypothesize that a dysfunction in adipose tissue growth may be a key factor in peripheral insulin resistance. Adipose tissue growth requires the recruitment and then the development of adipose precursor cells, but little is known about these processes in vivo. 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 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 μm) 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.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2010
Total Cost
$240,584
Indirect Cost
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Li, Yanjun; Periwal, Vipul; Cushman, Samuel W et al. (2016) Adipose cell hypertrophy precedes the appearance of small adipocytes by 3 days in C57BL/6 mouse upon changing to a high fat diet. Adipocyte 5:81-7
MacKellar, Jennifer; Cushman, Samuel W; Periwal, Vipul (2010) Waves of adipose tissue growth in the genetically obese Zucker fatty rat. PLoS One 5:e8197
Jo, Junghyo; Guo, Juen; Liu, Teresa et al. (2010) Hypertrophy-driven adipocyte death overwhelms recruitment under prolonged weight gain. Biophys J 99:3535-44
Jo, Junghyo; Gavrilova, Oksana; Pack, Stephanie et al. (2009) Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth. PLoS Comput Biol 5:e1000324
MacKellar, Jennifer; Cushman, Samuel W; Periwal, Vipul (2009) Differential effects of thiazolidinediones on adipocyte growth and recruitment in Zucker fatty rats. PLoS One 4:e8196