A high sugar diet, but not obesity, reduces female fertility in Drosophila melanogaster

Many studies from Drosophila to humans show a strong link between obesity and reduced fertility. However, obesity is often induced by changes in diet or eating behavior, such that it remains unclear whether reduced fertility is a consequence of obesity itself, diet, or both. Here, we report that a high sugar diet reduces Drosophila female fertility by increasing death of early germline cysts (prior to follicle formation) and degeneration of vitellogenic follicles; that obesity in and of itself does not impair fertility; and that high glucose levels closely correlate with reduced fertility on a high sugar diet. Females on a high sugar diet rapidly develop obesity (and display high glycogen, glucose, and trehalose levels, and insulin resistance) and decreased fertility. In stark contrast to high-sugar-obese females, females in which similar levels of obesity are induced by adipocyte-specific knockdown of anti-obesity genes brummer or adipose have normal fertility and sugar metabolic indicators. Remarkably, females on a high sugar diet supplemented with a separate source of water also have normal fertility and glucose levels, despite persistent obesity, high glycogen and trehalose levels, and insulin resistance markers. These results strengthen our conclusion that obesity itself does not impair fertility, show an inverse correlation between high glucose levels and fertility, and demonstrate that insulin signaling levels remain sufficiently high to maintain insulin-dependent processes during oogenesis irrespective of insulin resistance markers.