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

Obesity is linked to reduced fertility from Drosophila to humans. Considering that obesity is often induced by changes in diet or eating behavior, it remains unclear whether obesity, diet, or both reduce fertility. Here, we show that Drosophila females on a high sugar diet become rapidly obese and less fertile due to increased death of early germline cysts and vitellogenic egg chambers (or follicles). They also have high glycogen, glucose, and trehalose levels and develop insulin resistance in their fat bodies (but not ovaries). By contrast, females with adipocyte-specific knockdown of anti-obesity genes brummer or adipose are obese but have normal fertility. Remarkably, females on a high sugar diet supplemented with a separate source of water have mostly normal fertility and glucose levels, despite persistent obesity, high glycogen and trehalose levels, and fat body insulin resistance. These findings demonstrate that a high sugar diet affects specific processes in oogenesis independent of insulin resistance, that high glucose levels correlate with reduced fertility on a high sugar diet, and that obesity alone does not impair fertility.