Thermal lesions of the SCN do not abolish all gene expression rhythms in rat white adipose tissue, NAMPT remains rhythmic

Rianne Van Der Spek, Ewout Foppen, Eric Fliers, Susanne La Fleur, Andries Kalsbeek

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Obesity and type 2 diabetes mellitus are major health concerns worldwide. In obese-type 2 diabetic patients, the function of the central brain clock in the hypothalamus, as well as rhythmicity in white adipose tissue (WAT), are reduced. To better understand how peripheral clocks in white adipose tissue (WAT) are synchronized, we assessed the importance of the central brain clock for daily WAT rhythms. We compared gene expression rhythms of core clock genes (Bmal1, Per2, Cry1, Cry2, RevErbα, and DBP) and metabolic genes (SREBP1c, PPARα, PPARγ, FAS, LPL, HSL, CPT1b, Glut4, leptin, adiponectin, visfatin/NAMPT, and resistin) in epididymal and subcutaneous white adipose tissue (eWAT and sWAT) of SCN-lesioned and sham-lesioned rats housed in regular L/D conditions. Despite complete behavioral and hormonal arrhythmicity, SCN lesioning only abolished Cry2 and DBP rhythmicity in WAT, whereas the other clock gene rhythms were significantly reduced, but not completely abolished. We observed no major differences in the effect of SCN lesions between the two WAT depots. In contrast to clock genes, all metabolic genes lost their daily rhythmicity in WAT, with the exception of NAMPT. Interestingly, NAMPT rhythmicity was even less affected by SCN lesioning than the core clock genes, suggesting that it is either strongly coupled to the remaining rhythmicity in clock gene expression, or very sensitive to other external rhythmic factors. The L/D cycle could be such a rhythmic external factor that generates modulating signals by photic masking via the intrinsic photosensitive retinal ganglion cells in combination with the autonomic nervous system. Our findings indicate that in normal weight rats, gene expression rhythms in WAT can be maintained independent of the central brain clock.

Originele taal-2Engels
Pagina's (van-tot)1354-1366
Aantal pagina's13
TijdschriftChronobiology International
Volume38
DOI's
StatusGepubliceerd - jun 2021

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