Adipocyte development and insulin resistance

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

We apply the understanding obtained from previous studies to breast adipose tissue cell-size distributions obtained from a cohort of breast cancer patients, to quantitatively assess the relative contributions of hyperplasia and hypertrophy to the state of the cell-size probability distribution. We find that higher hyperplasia is correlated with shorter survival in obese women, but that women with lower BMI do not show a similar difference in survival. We and others have provided evidence that C-terminal binding protein (CtBP), an NADH-dependent transcriptional repressor that links carbohydrate metabolism to epigenetic regulation, may play a broad role in breast cancer biology by inducing mesenchymal and stem cell-like features. Murine models of obesity show a significant association between obesity, increased mammary gland density, and elevated CtBP expression. Moreover, higher CtBP expression is also predictive of poor clinical outcome, suggesting a compelling correlation between higher hyperplasia in breast adipose cell-size distributions and an increased risk of breast cancer incidence and progression.