ENDO2023: Mass General Study Identifies Sex Differences in Neurohormone Linked to Body Composition Interview with:



Francesca Galbiati, MD
Clinical/Research fellow in Endocrinology
Massachusetts General Hospital What is the background for this study?

Response:  Arginine-vasopressin (AVP) is a neurohormone well known for its role in water balance regulation. It promotes renal water absorption in the kidney, to maintain normal sodium levels in the blood via a tightly controlled osmotic regulation. Besides AVP classical role, data have shown that AVP effects extend beyond water balance regulation. Animal studies have shown that AVP has metabolic effects, including reducing food intake, inducing lipolysis, and promoting muscle regeneration in male mice.

Furthermore, AVP is regulated differently in males and females, and affects cognition differently across sexes, a phenomenon called sexual dimorphism. However, it is unknown whether its dimorphism translates to metabolism. Also, findings on AVP metabolic role are inconsistent, possibly due to the opposing effects of AVP at different receptor subtypes, which regulation is still largely unknown. We performed this study to better investigate AVP metabolic role, and explore sex differences. We hypothesized that AVP would be positively associated with BMI, adiposity, and lean mass (acting as a signal of energy availability). We also predicted that relationships between AVP and body composition measures would differ by sex. We used the AVP area under the curve around a standardized meal to better capture repeated measures in response to food intake (that directly impacts energy availability). This also allowed to avoid the possible risk of fluctuating AVP levels due to possible pulsatile secretion. What are the main findings?

Response:  Across all participants, AVP levels correlated positively with BMI (rs=0.36, p=0.008), total fat mass (r=0.33, p=0.013), truncal fat (r=0.35; p=0.010), abdominal subcutaneous fat (r=0.30, p=0.028), and total lean mass. When comparing males and females, a robust positive correlation between AVP levels and abdominal subcutaneous fat mass was present in males (r=0.56, p=0.004), but not females (r=0.04, p=0.592), highlighting a possible sexually dimorphic metabolic action of AVP. What should readers take away from your report?

Response: Our data in humans shows, first of all, a link between AVP and body composition, supporting that AVP is a metabolically active hormone. Additionally, we identified sex differences in the relationship between AVP and subcutaneous adiposity, indicating that sex-dependent mechanisms may underly AVP regulation of metabolism. What recommendations do you have for future research as a results of this study?

Response: AVP role goes well beyond water balance regulation, and it may exert crucial metabolic effects in humans. AVP physiologic role in metabolism is not well understood, and preclinical and clinical studies suggest an effect on food intake, glucose homeostasis, and body composition regulation. Physiology studies in humans to better elucidate AVP role in metabolism, body composition regulation, and potential disruptions in AVP signaling secondary to obesity are warranted. Furthermore, exploring sex differences in AVP signaling appears to be crucial. Is there anything else you would like to add? Any disclosures?

Response: Hypothalamic-pituitary neurohormones have been shown to affect functions that go beyond the classical description of these hormones’ role (sodium-water balance for AVP, lactation and parturition for oxytocin). In fact, large body of literature suggests that both hormones modulate mood, cognition, metabolism, and social function. There is a huge need for research in this field that may open to new understanding of several diseases and novel therapeutic avenues.

No financial disclosures


ENDO 2023 poster
Sex-specific and Shared Associations between Vasopressin Levels and Body Composition in Adults with Obesity (Poster)

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