This study investigates the impact of expanding subcutaneous adipose tissue on metabolic profiles in mice. The researchers hypothesized that the inability to expand subcutaneous adipose tissue may contribute to insulin resistance and β-cell failure. They found that overexpressing adiponectin in ob/ob mice, which lack leptin, led to normalized glucose and insulin levels, improved glucose tolerance, and reduced triglyceride levels. The transgenic mice displayed increased adipose tissue mass, particularly subcutaneous fat, without significant macrophage infiltration or systemic inflammation. These improvements were associated with increased PPARγ target gene expression and reduced hepatic steatosis. The study suggests that adiponectin acts as a "starvation signal," promoting the storage of triglycerides in adipose tissue, which in turn improves systemic insulin sensitivity. This novel model of morbid obesity with an improved metabolic profile highlights the potential therapeutic benefits of expanding subcutaneous adipose tissue.This study investigates the impact of expanding subcutaneous adipose tissue on metabolic profiles in mice. The researchers hypothesized that the inability to expand subcutaneous adipose tissue may contribute to insulin resistance and β-cell failure. They found that overexpressing adiponectin in ob/ob mice, which lack leptin, led to normalized glucose and insulin levels, improved glucose tolerance, and reduced triglyceride levels. The transgenic mice displayed increased adipose tissue mass, particularly subcutaneous fat, without significant macrophage infiltration or systemic inflammation. These improvements were associated with increased PPARγ target gene expression and reduced hepatic steatosis. The study suggests that adiponectin acts as a "starvation signal," promoting the storage of triglycerides in adipose tissue, which in turn improves systemic insulin sensitivity. This novel model of morbid obesity with an improved metabolic profile highlights the potential therapeutic benefits of expanding subcutaneous adipose tissue.