Molecular Mechanisms and Clinical Translation of Intermittent Fasting on Adipose Tissue Heterogeneity

Fan Yang

doi:10.54254/2753-8818/2025.LD25981

Theoretical and Natural ScienceOpen access

Molecular Mechanisms and Clinical Translation of Intermittent Fasting on Adipose Tissue Heterogeneity

Research Article

Open Access

Molecular Mechanisms and Clinical Translation of Intermittent Fasting on Adipose Tissue Heterogeneity

Fan Yang ^1*

¹ Beijing University of Chinese Medicine

^*Corresponding author: quejing@asu.edu.pl

Published on 13 August 2025

TNS Vol.122

ISSN (Print): 2753-8826

ISSN (Online): 2753-8818

ISBN (Print): 978-1-80590-269-0

ISBN (Online): 978-1-80590-270-6

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Abstract

Adipose tissue heterogeneity, particularly the pathogenic role of visceral adipose tissue (VAT) in metabolic diseases, poses significant clinical challenges. Current research confirms that intermittent fasting (IF) induces depot-specific adaptations: VAT exhibits lipid conservation mechanisms while subcutaneous adipose tissue (SAT) demonstrates thermogenic plasticity through microbiota crosstalk. The gut-liver axis further mediates systemic metabolic synchronization during IF. However, precise frameworks for stratifying IF protocols based on adipose biology remain underdeveloped. This review synthesizes molecular mechanisms driving VAT/SAT differential responses to IF, evaluates depot-specific efficacy of major regimens, and establishes a visceral fat ratio (VFR)-based precision framework. Key findings indicate that early time-restricted eating (eTRE) preferentially reduces VAT with glycemic stability, whereas alternate-day fasting (ADF) carries long-term rebound risks. Integration of circadian-aligned exercise and behavioral support significantly enhances intervention sustainability. This analysis provides clinically actionable stratification: high-VFR individuals benefit maximally from eTRE-exercise synergy, while moderate-VFR phenotypes require vigilant cardiometabolic monitoring during ADF. The framework addresses critical implementation barriers including lean mass preservation and adolescent contraindications. Future research should prioritize digital adherence platforms and biomarker-defined feeding windows to optimize personalization. This work establishes a mechanism-informed foundation for translating adipose-specific IF benefits while highlighting unresolved questions regarding long-term vascular impacts and tissue-specific circadian reprogramming.

Keywords:

Adipose Tissue Heterogeneity, Intermittent Fasting, Visceral Adipose Tissue, Precision Nutrition.

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References

[1]. Larance, M., et al. (2021). Proteomic analysis of adipose tissue adaptation to intermittent fasting. Cell Reports, 34(10), 108804.

[2]. Li, G., et al. (2022). Mitochondrial dysfunction drives visceral adiposity. Cell Metabolism, 35(3), 473–489.

[3]. Zhang, Q., et al. (2019). Microbial metabolite butyrate stimulates thermogenesis. Cell Metabolism, 30(2), 301–315.

[4]. Shi, L., et al. (2023). Human subcutaneous fat browning in response to time-restricted eating. Journal of Nutritional Biochemistry, 115, 109649.

[5]. Byrne, C. S., et al. (2020). Gut-derived short-chain fatty acids regulate liver metabolism. Nature Communications, 11(1), 1023.

[6]. Panda, S. (2016). Circadian regulation of metabolism. Science, 354(6315), 1008–1015.

[7]. Liu, R., et al. (2021). 5: 2 intermittent fasting reduces hepatic steatosis. Clinical Nutrition, 40(5), 789–800.

[8]. Cani, P. D., et al. (2009). Gut microbiota modulates endotoxin-induced inflammation. Diabetes, 58(6), 1476–1481.

[9]. Jamshed, H., et al. (2019). Early time-restricted feeding improves metabolic health. Cell Metabolism, 30(3), 448–457.

[10]. Harris, L., et al. (2021). Intermittent fasting versus daily calorie restriction. JAMA Internal Medicine, 181(8), 1046–1054.

[11]. Patterson, R. E., & Sears, D. D. (2017). Metabolic effects of intermittent fasting. Annual Review of Nutrition, 37, 371–393.

[12]. Tinsley, G. M., et al. (2020). Time-restricted eating plus resistance training. Obesity, 28(5), 860–869.

[13]. Patel, K., et al. (2022). Cognitive-behavioral therapy enhances intermittent fasting adherence. Annals of Behavioral Medicine, 56(2), 89–101.

[14]. Wilkinson, M. J., et al. (2020). Ten-hour time-restricted eating reduces weight and blood pressure. Cell Metabolism, 32(3), 366–378.

[15]. de Cabo, R., & Mattson, M. P. (2019). Effects of intermittent fasting on health and disease. New England Journal of Medicine, 381(26), 2541–2551.