Impact of Dietary Interventions on Adipocyte Epigenetic Regulation: A Systematic Review

Obesity and its associated metabolic disorders represent a major global public health challenge and are characterized by adipose tissue dysfunction, inflammation, insulin resistance, and altered metabolic regulation. Dietary exposures may influence these processes through epigenetic mechanisms; however, evidence obtained directly from human adipose tissue remains limited and heterogeneous. This systematic review aimed to evaluate the effects of dietary interventions and acute dietary exposures on epigenetic regulation in human adipose tissue and to examine their potential associations with adipose tissue function and metabolic health. A systematic search was conducted in PubMed and Scopus from database inception through 18 March 2026, without publication-date restrictions. Eligible publications involved adult human participants and evaluated a clearly defined dietary intervention or acute dietary exposure in relation to epigenetic markers measured directly in adipose tissue. Animal studies, in vitro investigations, reviews, conference abstracts, and publications without relevant adipose tissue epigenetic outcomes were excluded. Of 767 records identified, 458 unique records were screened, 55 full-text reports were assessed, and seven publications were included in the qualitative synthesis. Risk of bias was evaluated using RoB 2 for randomized trials and ROBINS-I for non-randomized studies. The included publications investigated acute mixed-meal intake, 36-hour fasting, short-term high-fat overfeeding, six-month energy restriction, energy-restricted diets differing in glycemic index and fat content, and folic acid plus vitamin B12 supplementation. All publications analyzed subcutaneous adipose tissue. DNA methylation was assessed in six publications, whereas one evaluated microRNA expression; none directly investigated histone modifications or chromatin accessibility. Dietary exposures were associated with epigenetic variation in genes and pathways related to insulin signaling, adipokine function, immune regulation, angiogenesis, and energy metabolism. Responses varied according to metabolic status, adiposity, birth weight, and individual weight-loss response. Small samples, heterogeneous interventions and analytical methods, missing outcome data, residual confounding, and possible selective reporting limited confidence in the findings. The available evidence suggests that the human subcutaneous adipose tissue epigenome is responsive to dietary exposure. However, it does not establish the superiority of a specific dietary intervention or demonstrate that the identified epigenetic changes cause improvements in metabolic health. Larger, adequately powered, and preregistered human studies incorporating standardized tissue collection, cell-specific analyses, functional validation, and long-term follow-up are required. Keywords: obesity; adipose tissue; epigenetics; dietary interventions; DNA methylation; microRNA; metabolic health; systematic review.