Latest trends on interplay of autophagy, adipose tissue, and gut microbiota in obesity-related metabolic disorders

Purpose of review: This review aims to synthesize current research on the intricate relationships among visceral obesity (VO), autophagy (Atg), gut microbiota, and adipose tissue dysfunction, all of which contribute significantly to insulin resistance (IR) and associated metabolic disorders. Specifi...

Full description

Saved in:
Bibliographic Details
Main Authors: Claudette Butoyi, Muhammad Asad Iqbal, Isaac Duah Boateng
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Human Nutrition & Metabolism
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666149725000167
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850195811868082176
author Claudette Butoyi
Muhammad Asad Iqbal
Isaac Duah Boateng
author_facet Claudette Butoyi
Muhammad Asad Iqbal
Isaac Duah Boateng
author_sort Claudette Butoyi
collection DOAJ
description Purpose of review: This review aims to synthesize current research on the intricate relationships among visceral obesity (VO), autophagy (Atg), gut microbiota, and adipose tissue dysfunction, all of which contribute significantly to insulin resistance (IR) and associated metabolic disorders. Specifically, it seeks to identify key mechanistic pathways and potential therapeutic targets. Findings: Contemporary investigations have established VO as a principal etiological factor in diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD), accounting for a substantial proportion of global metabolic disease incidence. Notable discoveries include: (1) the nuanced role of Atg in adipose tissue homeostasis, wherein tissue-specific aberrations, such as diminished ATG5 expression in visceral adipose tissue, exacerbate IR. Conversely, pharmacologically induced Atg, exemplified by rapamycin administration, enhances insulin sensitivity by 15–25 % in rodent models. (2) Alterations in gut microbial composition, characterized by a 40 % decrease in Bacteroidetes and an increase in Firmicutes, correlate with elevated visceral adiposity and systemic inflammation. Fecal microbiota transplantation in human studies has demonstrated restoration of microbial diversity, resulting in a 12 % reduction in hepatic steatosis in NAFLD patients; (3) adipose tissue macrophages exhibit a pro-inflammatory phenotype, evidenced by a 2-3-fold elevation in TNF-α levels in VO, which precipitates metabolic dysfunction through Toll-like receptor 4 and nuclear factor kappa B signaling pathways. Conclusion: The interactive network involving Atg, gut microbiota, and adipose tissue represents a pivotal axis in the development of metabolic diseases. While interventions targeting Atg and microbiota modulation demonstrate potential, inconsistent outcomes, such as the variable efficacy of probiotic therapies, underscore the context-dependent nature of these mechanisms. Existing therapeutic approaches, including lifestyle modifications, pharmacological interventions, and bariatric surgery, address adiposity but require more targeted approaches. Future research should prioritize elucidating tissue-specific Atg regulation and developing personalized microbiota-based therapies to manage the complex pathophysiology of obesity-related disorders effectively.
format Article
id doaj-art-045107b2cc644b4e84152639fd8dfceb
institution OA Journals
issn 2666-1497
language English
publishDate 2025-06-01
publisher Elsevier
record_format Article
series Human Nutrition & Metabolism
spelling doaj-art-045107b2cc644b4e84152639fd8dfceb2025-08-20T02:13:40ZengElsevierHuman Nutrition & Metabolism2666-14972025-06-014020031310.1016/j.hnm.2025.200313Latest trends on interplay of autophagy, adipose tissue, and gut microbiota in obesity-related metabolic disordersClaudette Butoyi0Muhammad Asad Iqbal1Isaac Duah Boateng2Department of Endocrinology and Metabolism, The Affiliated Hospital of Jiangsu University, Institute of Endocrine and Metabolic Diseases, Jiangsu University, Zhenjiang, Jiangsu, China; School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, China; Corresponding author. Department of Endocrinology and Metabolism, The Affiliated Hospital of Jiangsu University, Institute of Endocrine and Metabolic Diseases, Jiangsu University, Zhenjiang, Jiangsu, China.School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, ChinaCertified Group, 199 W Rhapsody Dr, San Antonio, TX, 78216, USAPurpose of review: This review aims to synthesize current research on the intricate relationships among visceral obesity (VO), autophagy (Atg), gut microbiota, and adipose tissue dysfunction, all of which contribute significantly to insulin resistance (IR) and associated metabolic disorders. Specifically, it seeks to identify key mechanistic pathways and potential therapeutic targets. Findings: Contemporary investigations have established VO as a principal etiological factor in diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD), accounting for a substantial proportion of global metabolic disease incidence. Notable discoveries include: (1) the nuanced role of Atg in adipose tissue homeostasis, wherein tissue-specific aberrations, such as diminished ATG5 expression in visceral adipose tissue, exacerbate IR. Conversely, pharmacologically induced Atg, exemplified by rapamycin administration, enhances insulin sensitivity by 15–25 % in rodent models. (2) Alterations in gut microbial composition, characterized by a 40 % decrease in Bacteroidetes and an increase in Firmicutes, correlate with elevated visceral adiposity and systemic inflammation. Fecal microbiota transplantation in human studies has demonstrated restoration of microbial diversity, resulting in a 12 % reduction in hepatic steatosis in NAFLD patients; (3) adipose tissue macrophages exhibit a pro-inflammatory phenotype, evidenced by a 2-3-fold elevation in TNF-α levels in VO, which precipitates metabolic dysfunction through Toll-like receptor 4 and nuclear factor kappa B signaling pathways. Conclusion: The interactive network involving Atg, gut microbiota, and adipose tissue represents a pivotal axis in the development of metabolic diseases. While interventions targeting Atg and microbiota modulation demonstrate potential, inconsistent outcomes, such as the variable efficacy of probiotic therapies, underscore the context-dependent nature of these mechanisms. Existing therapeutic approaches, including lifestyle modifications, pharmacological interventions, and bariatric surgery, address adiposity but require more targeted approaches. Future research should prioritize elucidating tissue-specific Atg regulation and developing personalized microbiota-based therapies to manage the complex pathophysiology of obesity-related disorders effectively.http://www.sciencedirect.com/science/article/pii/S2666149725000167Visceral obesityMetabolic disordersAutophagyGut microbiotaInsulin resistanceAdipose tissue dysfunction
spellingShingle Claudette Butoyi
Muhammad Asad Iqbal
Isaac Duah Boateng
Latest trends on interplay of autophagy, adipose tissue, and gut microbiota in obesity-related metabolic disorders
Human Nutrition & Metabolism
Visceral obesity
Metabolic disorders
Autophagy
Gut microbiota
Insulin resistance
Adipose tissue dysfunction
title Latest trends on interplay of autophagy, adipose tissue, and gut microbiota in obesity-related metabolic disorders
title_full Latest trends on interplay of autophagy, adipose tissue, and gut microbiota in obesity-related metabolic disorders
title_fullStr Latest trends on interplay of autophagy, adipose tissue, and gut microbiota in obesity-related metabolic disorders
title_full_unstemmed Latest trends on interplay of autophagy, adipose tissue, and gut microbiota in obesity-related metabolic disorders
title_short Latest trends on interplay of autophagy, adipose tissue, and gut microbiota in obesity-related metabolic disorders
title_sort latest trends on interplay of autophagy adipose tissue and gut microbiota in obesity related metabolic disorders
topic Visceral obesity
Metabolic disorders
Autophagy
Gut microbiota
Insulin resistance
Adipose tissue dysfunction
url http://www.sciencedirect.com/science/article/pii/S2666149725000167
work_keys_str_mv AT claudettebutoyi latesttrendsoninterplayofautophagyadiposetissueandgutmicrobiotainobesityrelatedmetabolicdisorders
AT muhammadasadiqbal latesttrendsoninterplayofautophagyadiposetissueandgutmicrobiotainobesityrelatedmetabolicdisorders
AT isaacduahboateng latesttrendsoninterplayofautophagyadiposetissueandgutmicrobiotainobesityrelatedmetabolicdisorders