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•Despite renewed emphasis of the importance of examining sex-specific effects in medical research, empirical studies examining multi-dimensional questions such as interacting effects of diet and behavior are still often restricted to males due to logistical constraints and perceived hormonally induced variability in females.•We outline why conclusions drawn from one sex cannot be extrapolated to the other, highlighting interactive effects among sex hormones, serotonin, and appetite as an illustrative example.•Due to the bi-directional nature of the relationship between obesity and mood disorders, the development of sex-specific dietary guidelines will aid in the treatment of both medical conditions.
Obesity and mood disorders are two of the most serious health issues of modern times. These health conditions are often linked, with obesity acting both as a cause and consequence of anxiety and depression. Although sex differences in the relationship between obesity and mood disorders are observed in clinical populations, the relative influence of biology versus societal conditioning is unclear. In part, this is because sex effects are rarely examined in the animal models used to derive our understanding of basic biological mechanisms. Due to the perceived confounding nature of hormonal fluctuations in females, rodent studies examining nutritional effects on behavioral responses are typically restricted to males. Yet, hormones play an important role in mediating effects of diet on behavior. In this mini-review, we outline interactions between obesity, hormones and the brain to illustrate the importance of considering sex-specific effects in studies of nutritional effects on behavior. We highlight the need for a more nuanced understanding of how dietary factors influence these relationships, arguing that such knowledge will help improve clinical health outcomes in the management of both obesity and mood disorders.