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 m) 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 in obesity. Early studies reported that the size of adipose cells correlates with insulin resistance. However, a recent study comparing moderately obese, sensitive and resistant subjects, with comparable body mass index (BMI, 30), did not detect any significant difference in the size of the large cells, but rather a smaller proportion of large cells in the resistant subjects, suggesting impaired adipogenesis. We hypothesize that a decreased proportion, rather than the size, of large adipose cells is also associated with insulin resistance in lean individuals. Thirty-five leaner (BMI 18 34) subjects who were healthy, but first degree relatives of type 2 diabetics, were recruited. Insulin sensitivity was measured by euglycemic, hyperinsulinemic clamp. Needle biopsies of abdominal subcutaneous fat were assayed for adipose cell size by fitting the cell size distribution with two exponentials and a Gaussian function. The fraction of large cells was defined as the area of the Gaussian peak and the size of the large cells was defined as its center (cp). Glucose infusion rate and cp were negatively correlated, but insulin sensitivity and the proportion of large cells were not correlated. BMI and cp were also strongly correlated, but a relationship of modest correlation between cell size and insulin resistance was still significant after correcting for BMI. In contrast to moderately obese subjects, in lean subjects both BMI and the size of the large adipose cells predict the degree of insulin resistance;no correlation is found between the proportion of large adipose cells and insulin resistance. We set out to confirm, in a large cohort with broad BMI distribution, whether insulin resistance, quantified in-vivo using gold standard techniques, is associated with larger adipose cell size and/or an increased proportion of small adipose cells, described using the Beckman Coulter method. In addition, we evaluated the contribution of increasing adipose cell size vs number to increasing body mass, and whether sex interactions played a role in the relationships evaluated. The results demonstrate that increased body fat is characterized by a dramatic increase in the number of adipose cells, and a modest increase in size of mature adipose cells. Thus, by the time an individual has attained a BMI of 25 kg/m2, the pool of mature adipose cells is close to maximal triglyceride fat storage capacity, and further cell enlargement contributes little to additional fat storage needs. Rather, new adipose cells are recruited and they mature into large cells such that the proportion of small to large cells remains constant. Relative accumulation of small adipose cells characterizes the insulin-resistant state. Whether these represent impaired fat uptake per se, or impaired terminal differentiation is unclear. That small adipose cells are associated with insulin resistance supports the hypothesis that we and others hold, contending that impaired subcutaneous fat storage is contributory in the development of whole body insulin resistance. Further studies are needed to delineate the underlying regulation of maximal triglyceride storage capacity, adipogenesis, and mediators of insulin resistance, and the unique biological properties of the small, as compared with large, adipose cells.

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McLaughlin, T; Lamendola, C; Coghlan, N et al. (2014) Subcutaneous adipose cell size and distribution: relationship to insulin resistance and body fat. Obesity (Silver Spring) 22:673-80
Guo, Hong; Bazuine, Merlijn; Jin, Daozhong et al. (2013) Evidence for the regulatory role of lipocalin 2 in high-fat diet-induced adipose tissue remodeling in male mice. Endocrinology 154:3525-38
Kursawe, Romy; Caprio, Sonia; Giannini, Cosimo et al. (2013) Decreased transcription of ChREBP-?/? isoforms in abdominal subcutaneous adipose tissue of obese adolescents with prediabetes or early type 2 diabetes: associations with insulin resistance and hyperglycemia. Diabetes 62:837-44
Yang, Jian; Eliasson, Bjorn; Smith, Ulf et al. (2012) The size of large adipose cells is a predictor of insulin resistance in first-degree relatives of type 2 diabetic patients. Obesity (Silver Spring) 20:932-8
MacKellar, Jennifer; Cushman, Samuel W; Periwal, Vipul (2010) Waves of adipose tissue growth in the genetically obese Zucker fatty rat. PLoS One 5:e8197
Santoro, Nicola; Kursawe, Romy; D'Adamo, Ebe et al. (2010) A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents. Hepatology 52:1281-90
McLaughlin, Tracey M; Liu, T; Yee, Gail et al. (2010) Pioglitazone increases the proportion of small cells in human abdominal subcutaneous adipose tissue. Obesity (Silver Spring) 18:926-31
Kursawe, Romy; Eszlinger, Markus; Narayan, Deepak et al. (2010) Cellularity and adipogenic profile of the abdominal subcutaneous adipose tissue from obese adolescents: association with insulin resistance and hepatic steatosis. Diabetes 59:2288-96
Daigle Jr, Bernie J; Deng, Alicia; McLaughlin, Tracey et al. (2010) Using pre-existing microarray datasets to increase experimental power: application to insulin resistance. PLoS Comput Biol 6:e1000718
McLaughlin, T; Deng, A; Yee, G et al. (2010) Inflammation in subcutaneous adipose tissue: relationship to adipose cell size. Diabetologia 53:369-77

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