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β3-Adrenergic Receptor Agonism: A Novel Therapeutic Strategy for Metabolic Dysfunction in Polycystic Ovary Syndrome

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Abstract

Purpose

Beta-3 adrenergic receptors play a significant role in regulating energy utilization and metabolism, lipid mobilization, and sensitivity of insulin. They are the most relevant target in metabolic disorders such as obesity, type 2 diabetes mellitus, and dyslipidemia. The B3 receptors are mainly present in brown adipose tissue, at where their activation increases thermogenesis through uncoupling protein 1, increasing energy expenditure, and in white adipose tissue, enhancing lipolysis in WAT, thus reducing fat accumulation.

Methodology

Using the databases PubMed, Google Scholar, Medline, and Embase, a systematic literature review was conducted. The data was collected by employing these databases providing the therapeutic role of beta-3 agonists in metabolic disorders. The articles were examined using Rayyan, an online tool, to ensure an efficient and thorough review process.

Results

The present review points towards the therapeutic role of stimulating β3-AR in metabolic syndromes, especially in PCOS, by enhancing insulin sensitivity, improving lipid metabolism, and dampening inflammation. β3-AR agonists promote thermogenesis and fat oxidation, contributing to weight control, an important determinant of PCOS management. Polymorphisms in ADRB3 in genetic studies affect metabolic responses, which hint at the possibility of tailored therapy.

Conclusion

In summary, β3-AR-targeted treatments have great potential to improve metabolic dysfunction in PCOS by tackling the major problems of inflammation, obesity, and insulin resistance. β3-AR agonists may represent a promising but still experimental avenue for managing metabolic dysfunction in PCOS. However, no clinical trials in women with PCOS have been conducted, and their potential role should be regarded as hypothesis-generating until validated by further clinical research.

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Data Availability

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Code Availability

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Abbreviations

β3:

Beta-3

AR:

Adrenergic receptor

PCOS:

Polycystic ovarian syndrome

T2DM:

Type 2 diabetes mellitus

BAT:

Brown adipose tissue

UCP1:

Uncoupling protein 1

WAT:

White adipose tissue

TME:

Tumor microenvironment

ADRB3:

Beta-3 adrenergic receptor gene

AC:

Adenylate cyclase

cAMP:

Cyclic adenosine monophosphate

PKA:

Protein kinase A

β-ARK:

Beta-adrenergic receptor kinase

GPCR:

G protein–coupled receptor

HOMA-IR:

Homeostatic Model Assessment for Insulin Resistance

OAB:

Overactive bladder

SEC:

Southeastern European Caucasian

ATP:

Adenosine triphosphate

ADP:

Adenosine diphosphate

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

nOH:

Neurogenic orthostatic hypotension

IBS:

Irritable bowel syndrome

QT/QTc:

Corrected QT interval

AUC:

Area under the curve

SNP:

Single nucleotide polymorphism

LDL:

Low-density lipoprotein

HDL:

High-density lipoprotein

NAFLD:

Non-alcoholic fatty liver disease

CAD:

Coronary artery disease

BMI:

Body mass index

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  1. Amity Institute of Pharmacy, Amity University, Noida, 201313, Uttar Pradesh, India

    Bhawna Chhabra, Gautam Saxena, Aditya Srivastava, Nakul Mahawar & Havagiray Chitme

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Bhawna Chhabra conducted the comprehensive literature review, drafted the entire manuscript, Aditya Srivastava and Nakul Mahawar created all tables and graphical elements that support the review’s content and structure. Gautam saxena contributed by reviewing the manuscript, making corrections, and editing the text to enhance clarity and coherence. Dr. Havagiray R. Chitme provided valuable insights on PRISMA formatting of paper and expert guidance to both the author and co-author and performed the final proofreading to ensure accuracy and depth of content.

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Chhabra, B., Saxena, G., Srivastava, A. et al. β3-Adrenergic Receptor Agonism: A Novel Therapeutic Strategy for Metabolic Dysfunction in Polycystic Ovary Syndrome. SN Compr. Clin. Med. 7, 323 (2025). https://doi.org/10.1007/s42399-025-02099-5

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