Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity

Sep 29, 2026

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Obesity is a major global public health problem marked by rising prevalence, high morbidity and mortality, and metabolic abnormalities including dyslipidemia, insulin resistance, diabetes, and cardiovascular diseases. Current interventions—lifestyle change, surgery, and pharmacological therapies—have limited effects on reducing energy stored in adipose tissue. White-to-brown adipose conversion, especially BAT loss in obesity, is a promising therapeutic direction. Neuroendocrine systems and the gut-brain axis (GBA) are summarized as key regulators linking energy balance to obesity onset and pathogenesis.

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CategoryHealthcare

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Abstract

Introduction

Obesity as an imbalance of energy intake and expenditure

Roles of white adipose tissue and brown adipose tissue

The gut-brain axis (GBA)

Submitted 9 January 2025 Accepted 27 October 2025 Published 2 January 2026 Corresponding author Wenge Chen, [chenwengebangong@163.com](chenwengebangong@163.com) Academic editor Lesley Anson Additional Information and Declarations can be found on page 24 DOI 10.7717/peerj.20400 Copyright 2026 Zhao et al. Distributed under Creative Commons CC-BY-NC 4.0 OPEN ACCESS Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity Hanwei Zhao1 , Yaqing Li1 , Ran Cheng1 , Ye Wang1 , Liyuan Ma2 and Wenge Chen1 1 The First Affiliated Hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin, China 2 Heilongjiang University of Traditional Chinese Medicine, Harbin, China ABSTRACT Obesity is a major global public health issue due to its high morbidity and mortality rates, with its prevalence increasing annually. According to World Health Organization (WHO) estimates, the global population of individuals with obesity has doubled from 1990 to 2022, with over 650 million adults with obesity experiencing metabolic abnormalities such as dyslipidemia, insulin resistance, diabetes, and cardiovascular diseases. Various approaches have been used to treat or prevent obesity including lifestyle interventions, surgery, and pharmacological therapies aimed at reducing energy absorption and increasing energy expenditure. However, these methods do not significantly reduce energy stored in adipose tissues. The conversion of white adipose tissue (WAT) to brown adipose tissue (BAT) presents a promising therapeutic target for obesity treatment. Notably, there is a substantial loss of BAT in individuals with obesity. Conversely, increased BAT is associated with a lower body mass index (BMI), younger age, lower glucose levels, and a decreased incidence of cardiometabolic diseases. Research indicates that BAT formation is modulated by neuro endocrine systems, suggesting a promising therapeutic strategy for obesity prevention and treatment by targeting these systems. In this review, we first discuss the regulation and signaling pathways of neuroendocrine systems involved in energy balance. We then explore the molecular and cellular mechanisms underlying the onset and pathogenesis of obesity and their relationship with neuroendocrine systems. In particular, we summarize the role of the gut-brain axis (GBA) in obesity. Subjects Diabetes and Endocrinology, Neurology, Obesity Keywords Obesity, Neuro-endocrine systems, White adipose tissues, Brown adipose tissues, Gut-Brain axis INTRODUCTION Obesity originates from an imbalance between caloric intake and energy expenditure, promoting the expansion of subcutaneous adipose tissue (SAT) and the excessive accumulation of visceral adipose tissue (VAT) (Seravalle & Grassi, 2017) . Obesity can trigger changes in hormone secretion and chronic inflammation (Marcelin et al., 2019) . It can also lead to chronic metabolic dysfunction, inducing diseases such as diabetes, hypertension, fatty liver, cardiovascular diseases, and gastrointestinal cancers (Piché, Tchernof & Després, 2020 ; Zou & Pitchumoni, 2023). Over the past century, as the economy How to cite this article Zhao H, Li Y, Cheng R, Wang Y, Ma L, Chen W. 2026. Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity. PeerJ 14:e20400 [http://doi.org/10.7717/peerj.20400](http://doi.org/10.7717/peerj.20400) has thrived, the population of individuals with obesity has increased sharply due to improved living standards, medical treatments (hypoglycemic drugs, glucocorticoid drugs, antidepressant drugs, etc.), and diet quality (high-calorie and low-nutrition) . Current estimates suggest that by 2025, more than 21% of women worldwide will be obese (Postonet al., 2016; Steinbach et al., 2024). The obese population tends to be younger, representing a global public health crisis. By 2022, 160 million children and adolescents were living with obesit

FAQs

Why is obesity considered a major global public health issue?

Obesity is linked to high morbidity and mortality and is increasingly prevalent worldwide, with many people developing metabolic abnormalities such as dyslipidemia, insulin resistance, diabetes, and cardiovascular diseases.

How might converting white adipose tissue (WAT) to brown adipose tissue (BAT) help regulate obesity?

WAT conversion to BAT is presented as a promising therapeutic target because increased BAT correlates with lower BMI and better cardiometabolic profiles, while obesity is associated with substantial BAT loss.

What roles do neuroendocrine systems and the gut-brain axis (GBA) play in obesity?

The review highlights that neuroendocrine systems modulate BAT formation and energy balance, and it emphasizes the GBA as a bidirectional communication network connecting gut and brain through neural, immune, and endocrine pathways relevant to obesity development.

Sep 29, 2026

Uploaded by Bulrr