Hyperinsulinemia is associated with obesity and pancreatic islet hyperplasia, but whether insulin causes these phenomena or is a compensatory response has remained unsettled for decades...we provide genetic evidence that pathological circulating hyperinsulinemia drives diet-induced obesity and its complications.

When we eat too much, obesity may develop as a result of chronically high insulin levels, not the other way around. That's according to new evidence in mice reported in the December 4th Cell Metabolism, a Cell Press publication, which challenges the widespread view that rising insulin is a secondary consequence of obesity and insulin resistance...The new study helps to solve this chicken-or-the-egg dilemma by showing that animals with persistently lower insulin stay trim even as they indulge themselves on a high-fat, all-you-can-eat buffet. The findings come as some of the first direct evidence in mammals that circulating insulin itself drives obesity, the researchers say.