Highlights from ‘Food and the brain' top early download review article
A recent review article published by Naira da Silva Mansano, Calvin Vinh Lieu and Alfonso Abizaid in Journal of Neuroendocrinology has had high early downloads. We asked lead author Naira da Silva Mansano to give us the highlights:
What is the main message of your review article?
Our article, Food and the brain: Neural and endocrine control of feeding, metabolism, and reproduction reviews key topics on the regulation and integration of feeding behavior and reproductive function systems, as discussed during a symposium presented at the 2023 Panamerican Neuroendocrine Society (PANS) meeting in Santos, Brazil, showing how important of scientific meetings are for sharing ideas, fostering discussion, and advancing collaborative research.
Our review highlights that feeding behavior and reproductive function are regulated by tightly integrated neuroendocrine systems that sense energy availability and adjust reproductive activity accordingly. This coordination is especially critical in female mammals, where reproduction requires substantial energetic investment.
The hypothalamus plays a central role by integrating peripheral metabolic signals and translating them into coordinated changes in feeding and reproductive physiology. During development, particularly before puberty, hormones such as leptin and insulin signal energy sufficiency and act as permissive cues for pubertal onset through activation of hypothalamic reproductive pathways. In adulthood, these hormones continue to regulate energy homeostasis while supporting normal reproductive function.
In contrast, ghrelin signals energy deficiency by stimulating hunger and reducing energy expenditure via hypothalamic and extrahypothalamic circuits, leading to suppression of reproductive processes. Together, these opposing hormonal actions illustrate how the brain integrates metabolic signals to coordinate energy balance and fertility.
The review also shows the clinical relevance of these mechanisms, identifying potential therapeutic targets for obesity and metabolic disorders. Understanding how metabolic hormones act on central neural circuits may enable treatments that improve metabolic health without compromising reproductive function, highlighting the fundamental link between energy status, brain regulation, and reproductive health.
Why is it important?
Studying the interaction between energy balance and reproductive function is critical because reproduction is one of the most energetically demanding physiological processes and is tightly regulated by metabolic status. Understanding how the brain integrates metabolic signals to coordinate feeding and reproduction is therefore essential for explaining normal development, maintaining adult health, and identifying mechanisms underlying disease.
This line of research is particularly important for understanding the timing of puberty, especially in females. Pubertal onset requires adequate energy reserves, and disruptions in metabolic signaling can lead to delayed or precocious puberty. In the context of the global rise in childhood obesity and metabolic disorders, elucidating how metabolic hormones such as leptin and insulin act on hypothalamic circuits to initiate reproductive maturation has major implications for pediatric and adolescent health.
Metabolic and reproductive disorders also frequently coexist. Conditions such as obesity, anorexia nervosa, polycystic ovary syndrome (PCOS), and hypothalamic amenorrhea are characterized by altered energy balance and impaired fertility. Investigating the neuroendocrine mechanisms linking metabolism and reproduction helps explain how nutritional states influence ovulation, menstrual cyclicity, and overall reproductive capacity.
Importantly, there is a sex-specific vulnerability to metabolic disease, as female reproductive physiology is uniquely sensitive to energy availability across the lifespan. Moreover, many anti-obesity therapies target neural circuits that overlap with those controlling reproduction, underscoring the need for therapeutic strategies that effectively regulate metabolism while preserving hormonal and reproductive health.
What's next for this area of research?
I recently returned to my home country and am currently in my second postdoctoral position at the University of Brasilia (Brazil). My research focuses on understanding how 17α-estradiol (17α-E2) modulates systemic and central metabolic regulation and protects against high-fat diet–induced metabolic and cognitive dysfunction in aging females. I investigate the diet-dependent effects of 17α-E2 on brain mitochondrial bioenergetics, highlighting a critical interaction between estrogen signaling, dietary lipid overload, and neuroendocrine circuits that regulate metabolism and behavior during aging. By elucidating these mechanisms, my work provides important insight into the potential role of hormonal supplementation in mitigating metabolic decline and neurodegenerative processes, including the development and progression of Alzheimer’s disease in postmenopausal women.
