Circadian clock dysfunction in human omental fat links obesity to metabolic inflammation.
Eléonore MauryBenoit NavezSonia M BrichardPublished in: Nature communications (2021)
To unravel the pathogenesis of obesity and its complications, we investigate the interplay between circadian clocks and NF-κB pathway in human adipose tissue. The circadian clock function is impaired in omental fat from obese patients. ChIP-seq analyses reveal that the core clock activator, BMAL1 binds to several thousand target genes. NF-κB competes with BMAL1 for transcriptional control of some targets and overall, BMAL1 chromatin binding occurs in close proximity to NF-κB consensus motifs. Obesity relocalizes BMAL1 occupancy genome-wide in human omental fat, thereby altering the transcription of numerous target genes involved in metabolic inflammation and adipose tissue remodeling. Eventually, clock dysfunction appears at early stages of obesity in mice and is corrected, together with impaired metabolism, by NF-κB inhibition. Collectively, our results reveal a relationship between NF-κB and the molecular clock in adipose tissue, which may contribute to obesity-related complications.
Keyphrases
- adipose tissue
- insulin resistance
- genome wide
- high fat diet induced
- oxidative stress
- signaling pathway
- weight loss
- metabolic syndrome
- high fat diet
- lps induced
- endothelial cells
- nuclear factor
- type diabetes
- weight gain
- pi k akt
- obese patients
- bariatric surgery
- dna methylation
- induced pluripotent stem cells
- skeletal muscle
- pluripotent stem cells
- dna damage
- roux en y gastric bypass
- body mass index
- rna seq
- risk factors
- toll like receptor
- circulating tumor cells
- inflammatory response
- clinical practice
- immune response
- heat shock protein
- drug induced
- high throughput sequencing