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Review
. 2024 Jan 1;56(1):1-8.
doi: 10.1152/physiolgenomics.00056.2023. Epub 2023 Nov 13.

Adenylate cyclase 3: a potential genetic link between obesity and major depressive disorder

Mackenzie Fitzpatrick  1 , Leah C Solberg Woods  1
Affiliations
Review

Adenylate cyclase 3: a potential genetic link between obesity and major depressive disorder

Mackenzie Fitzpatrick et al. Physiol Genomics. .

Abstract

Obesity and major depressive disorder (MDD) are both significant health issues that have been increasing in prevalence and are associated with multiple comorbidities. Obesity and MDD have been shown to be bidirectionally associated, and they are both influenced by genetics and environmental factors. However, the molecular mechanisms that link these two diseases are not yet fully understood. It is possible that these diseases are connected through the actions of the cAMP/protein kinase A (PKA) pathway. Within this pathway, adenylate cyclase 3 (Adcy3) has emerged as a key player in both obesity and MDD. Numerous genetic variants in Adcy3 have been identified in humans in association with obesity. Rodent knockout studies have also validated the importance of this gene for energy homeostasis. Furthermore, Adcy3 has been identified as a top candidate gene and even a potential blood biomarker for MDD. Adcy3 and the cAMP/PKA pathway may therefore serve as an important genetic and functional link between these two diseases. In this mini-review, we discuss the role of both Adcy3 and the cAMP/PKA pathway, including specific genetic mutations, in both diseases. Understanding the role that Adcy3 mutations play in obesity and MDD could open the door for precision medicine approaches and treatments for both diseases that target this gene.

Keywords: adenylate cyclase 3; cAMP; genetic variants; major depressive disorder; obesity.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Adenylate cyclase 3 (ADCY3) signaling pathways in the brain and adipose tissue. ADCY3 plays a role in the leptin-melanocortin pathway in the brain and in the β3-adrenergic receptor (β3-AR) pathway in adipose tissue. ADCY3 also plays an important role in olfactory sensory neurons, which is not pictured (see text for references). This figure was created with BioRender.com. α-MSH, α-melanocyte stimulating hormone; CREB, cAMP response element-binding protein; MC4R, melanocortin 4 receptor; R, regulatory subunit of protein kinase A; UCP1, uncoupling protein 1.
See this image and copyright information in PMC

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