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

**Authors:** Maria-Daniela Tanasescu, Andrei-Mihnea Rosu, Alexandru Minca, Maria-Mihaela Grigorie, Delia Timofte, Dorin Ionescu

PMC · DOI: 10.3390/life16020305 · 2026-02-10

## 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.

## Key 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.

## Linked entities

- **Diseases:** cardiovascular disease (MONDO:0004995), atherosclerosis (MONDO:0005311), heart failure (MONDO:0005252)

## Full-text entities

- **Genes:** SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, Bmal1 (basic helix-loop-helix ARNT like 1) [NCBI Gene 11865] {aka Arnt3, Arntl, BMAL1b, MOP3, bHLHe5, bmal1b'}, CRY2 (cryptochrome circadian regulator 2) [NCBI Gene 1408] {aka HCRY2, PHLL2}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, TRE-TTC3-1 (tRNA-Glu (anticodon TTC) 3-1) [NCBI Gene 7193] {aka TRE, TRNAE1, TRNE}, NR1D1 (nuclear receptor subfamily 1 group D member 1) [NCBI Gene 9572] {aka EAR1, REVERBA, REVERBalpha, THRA1, THRAL, ear-1}, PER2 (period circadian regulator 2) [NCBI Gene 8864] {aka FASPS, FASPS1}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, SAT1 (spermidine/spermine N1-acetyltransferase 1) [NCBI Gene 6303] {aka DC21, KFSD, KFSDX, SAT, SSAT, SSAT-1}, BMAL1 (basic helix-loop-helix ARNT like 1) [NCBI Gene 406] {aka ARNTL, ARNTL1, BMAL1c, JAP3, MOP3, PASD3}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Agt (angiotensinogen) [NCBI Gene 11606] {aka AngI, AngII, Aogen, Serpina8}, MTNR1B (melatonin receptor 1B) [NCBI Gene 4544] {aka FGQTL2, MEL-1B-R, MT2}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, PER1 (period circadian regulator 1) [NCBI Gene 5187] {aka PER, RIGUI, hPER}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CLOCK (clock circadian regulator) [NCBI Gene 9575] {aka KAT13D, bHLHe8}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** HFpEF (MESH:D054144), glucose (MESH:D018149), Instability (MESH:D043171), ectopic lipid (MESH:D011017), remodeling (MESH:D020257), coronary artery disease (MESH:D003324), low- (MESH:D009800), cardiac dysfunction (MESH:D006331), inflammatory cytokines (MESH:D000080424), type 2 diabetes (MESH:D003924), heart failure (MESH:D006333), EAT (MESH:D018205), vascular dysfunction (MESH:D002561), MUNW (MESH:D015431), impaired diastolic function (MESH:D006337), insulin resistance (MESH:D007333), myocardial infarction (MESH:D009203), leptin resistance (OMIM:614962), Cardiovascular Disease (MESH:D002318), adipocyte hypertrophy (MESH:D006984), atrial fibrillation (MESH:D001281), hypertension (MESH:D006973), impaired glucose regulation (MESH:C565631), atherogenesis (MESH:D050197), Hypoxia (MESH:D000860), visceral adiposity (MESH:D007418), metabolic dysregulation (MESH:D021081), metabolic (MESH:D008659), lipodystrophy (MESH:D008060), arrhythmic (OMIM:212500), overweight (MESH:D050177), stroke (MESH:D020521), hepatic steatosis (MESH:D005234), diastolic dysfunction (MESH:D018487), weight gain (MESH:D015430), arrhythmia (MESH:D001145), circadian misalignment (MESH:D017760), Obesity (MESH:D009765), endothelial dysfunction (MESH:D014652), cancer (MESH:D009369), Sleep (MESH:D012893), atrial remodeling (MESH:D064752), dyslipidemia (MESH:D050171), MHO (MESH:D000067329), atherometabolic disease (MESH:D004194), injury to (MESH:D014947), adipose inflammation (MESH:D007249), fibrosis (MESH:D005355), hyperglycemia (MESH:D006943), cardiometabolic abnormalities (MESH:D024821)
- **Chemicals:** glucose (MESH:D005947), NAD+ (MESH:D009243), sphingolipids (MESH:D013107), Lipid (MESH:D008055), fatty acid (MESH:D005227), SR9009 (MESH:C572451), glycerol (MESH:D005990), PVAT (-), Melatonin (MESH:D008550), NO (MESH:D009614), nitric oxide (MESH:D009569), free fatty acid (MESH:D005230), acetylcholine (MESH:D000109), phospholipids (MESH:D010743), triglyceride (MESH:D014280), oxygen (MESH:D010100)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** rs2314339

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941584/full.md

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Source: https://tomesphere.com/paper/PMC12941584