Increased stress tolerance in female fruit flies is associated with differences in adipose tissue gene expression – Gene to Genome

Studies show that differences between biological males and females extend far beyond the reproductive organs, and affect biology at many levels in many species.

These differences include variation in metabolism and susceptibility to disease. For example, the incidence of severe obesity is significantly higher in human females, putting women at risk for several diseases associated with obesity, while males are at higher risk for diabetes and insulin resistance. At least some of the differences in metabolism can be linked to the different nature of adipose tissue in men and women. Although efforts have been made to understand these differences, their molecular basis remains to be elucidated.

In a recently published study, researchers used fruit flies. Drosophila melanogaster To better understand sex-based differences in gene expression in adipose tissue, which performs functions similar to fat and liver in fruit flies.

They built on previous studies that showed increased resistance to a variety of stressors. Drosophila Women and discovered previously studied pathways, particularly the Integrated Stress Response (ISR) signaling pathway, which functions through the transcription factor ATF4.

Using various markers and reporters that reflect ATF4 activity, the researchers showed that female larval fat bodies have significantly higher ATF4 activity than males. In further experiments that changed the sex identity of adipocytes (fat cells) by genetically manipulating sex-differentiation gene expression only in adipocytes, thereby masculinizing female adipocytes or feminizing male adipocytes, they showed that sex-dependent differences in ATF4 affect the fat cells of these bodies. Differentiated cell sex identity on ATF4 cannot be excluded).

Among other functions, ATF4 plays a role in nutritional stress. For example, previous research has shown activation of the ISR and induction of ATF4 expression following dietary methionine deprivation. However, in these studies, nutrients were depleted throughout the animal. These researchers used genetic models to deplete methionine specifically in adipocytes. When methionine was depleted in adipose tissue during development, males exhibited significantly higher developmental lethality than females, supporting the hypothesis that females are more resistant to fat body-specific methionine depletion. Subsequent experiments suggested that the greater resilience to methionine deficiency in females depends on both the sex identity of adipocytes and higher ATF4 expression in adipocytes.

This study demonstrates the sex-specific role of the transcription factor ATF4 in fruit fly adipocytes and its contribution to the female-specific increase in resistance to methionine deficiency. In a broader context, an understanding of the molecular processes that govern sex-dependent energy metabolism may improve the understanding of sex differences in disease susceptibility and progression.