Adipose Tissue Circadian Dysregulation Beyond BMI: Implications for Cardiometabolic Risk and Cardiovascular Disease

TL;DR

This paper explores how the body's fat tissue clock affects heart and metabolic health, beyond just body mass index.

Contribution

It highlights how circadian misalignment in fat tissue contributes to cardiovascular disease and metabolic risk independently of BMI.

Findings

Adipose tissue circadian clocks regulate lipid and metabolic rhythms aligned with sleep and feeding cycles.

Circadian disruption in fat tissue leads to dysfunction, inflammation, and increased cardiometabolic risk.

Chronodisruption in fat depots is linked to insulin resistance, atherosclerosis, and heart failure.

Abstract

Cardiometabolic and cardiovascular risks are commonly assessed using body mass index (BMI) and static measures of adiposity; however, individuals with similar BMI frequently exhibit markedly different metabolic and cardiovascular outcomes. This heterogeneity reflects not only differences in fat distribution but also variation in adipose tissue function and its temporal regulation. Adipose tissue contains intrinsic circadian clocks that coordinate daily rhythms in lipid storage and mobilization, insulin sensitivity, adipokine secretion, and immune activity in alignment with sleep–wake and feeding–fasting cycles. Circadian misalignment, as occurs with shift work, irregular sleep, or mistimed food intake, disrupts this coordination and promotes adipose tissue dysfunction characterized by impaired rhythmic lipid handling, altered endocrine signaling, inflammation, fibrosis, and oxidative stress. Emerging evidence suggests that circadian dysregulation may differentially affect adipose depots, including visceral, epicardial, and perivascular fat, thereby linking chronodisruption to insulin resistance, endothelial dysfunction, atherosclerosis, heart failure phenotypes, and arrhythmia susceptibility. This narrative review synthesizes human, experimental, and translational studies examining adipose tissue circadian regulation as a functional determinant of cardiometabolic and cardiovascular risk beyond BMI. We also discuss the clinical implications of circadian-informed strategies, including chrononutrition and time-restricted eating, as potential tools to improve risk stratification and cardiometabolic health.

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