DNA Methylation Changes are Associated with the Programming of White Adipose Tissue Browning Features by Resveratrol and Nicotinamide Riboside Neonatal Supplementations in Mice

Abstract

Neonatal supplementation with resveratrol (RSV) or nicotinamide riboside (NR) programs in male mice brown adipocyte-like features in white adipose tissue (WAT browning) together with improved metabolism in adulthood. We tested the involvement in this programming of long-term epigenetic changes in two browning-related genes that are overexpressed in WAT of supplemented mice, Slc27a1 and Prdm16. Suckling mice received orally the vehicle, RSV or NR from postnatal days 2-to-20. After weaning (d21) onto a chow diet, male mice were habituated to a normal-fat diet (NFD) starting d75, and split on d90 into continuation on the NFD or switching to a high-fat diet (HFD) until euthanization on d164. CpG methylation by bisulfite-sequencing was analyzed on inguinal WAT. Both treatments modified methylation marks in Slc27a1 and Prdm16 and the HFD-dependent dynamics of these marks in the adult WAT, with distinct and common effects. The treatments also affected gene expression of de novo DNA methylases in WAT of young animals (euthanized at d35 in independent experiments). Studies in 3T3-L1 adipocytes indicated the direct effects of RSV and NR on the DNA methylation machinery and favoring browning features. The results support epigenetic effects being involved in WAT programming by neonatal RSV or NR supplementation in male mice.

The Impact of DNA Methylation on IL6 mRNA Levels in Hematinic Deficiency and Atopy-Associated Recurrent Aphthous Stomatitis Patients

“…The pellet was then dissolved with 50 µ l TE buffer pH 8. The bisulfite-converted protocol was carried out using the Zymo EZ DNA Methylation-Gold kit® catalog D5005 [ 43 , 44 ].…”

“…e alcohol is then discarded, and the tube is allowed to dry by turning it over the tissue until the alcohol evaporates. e pellet was then dissolved with 50 µl TE buffer pH 8. e bisulfiteconverted protocol was carried out using the Zymo EZ DNA Methylation-Gold kit ® catalog D5005 [43,44].…”

Emerging roles of epigenetic regulation in obesity and metabolic disease

“…For instance, clinical studies revealed that obesity-related metabolic parameters such as T2D status and BMI are closely associated with WAT DNA methylation ( 34 , 35 , 36 , 37 , 38 ). Studies using various mouse models with impaired DNA methylation further indicate the crucial roles of DNA methylation in WAT inflammation, WAT insulin resistance, and browning ( 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ).…”

“…Studies using various mouse models with impaired DNA methylation further indicate the crucial roles of DNA methylation in WAT inflammation, WAT insulin resistance, and browning ( 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ).…”

Nicotinamide Protects Against Diet‐Induced Body Weight Gain, Increases Energy Expenditure, and Induces White Adipose Tissue Beiging

“…[10,12,21] Despite this, [15] the mechanisms accounting for the broad spectrum of their health benefits are still poorly understood. Compelling data indicate that NAD + -raising strategies induce beiging in vivo; [22][23][24] however, the favorable contribution of nicotinamide (NAM), as an NAD + precursor, to adipose energy metabolism and beiging has not been previously assessed in vivo.…”