Programming of the Beige Phenotype in White Adipose Tissue of Adult Mice by Mild Resveratrol and Nicotinamide Riboside Supplementations in Early Postnatal Life

Abstract

RSV and NR supplementations in early postnatal life affect WAT's thermogenic/oxidative transcriptional phenotype and metabolic responses in adulthood, with upregulatory and beneficial effects evidenced in male animals.

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

“…DNA methylation analyses were conducted on inguinal WAT (iWAT) samples from previously phenotypically characterized cohorts of adult male mice that were supplemented during the suckling period with RSV or NR, and their non-supplemented controls. The study design is described in detail elsewhere [6]. The animal protocols were reviewed and approved by the Bioethical Committee of the University of the Balearic Islands (Ref.…”

“…Briefly, newborn NMRI mice in size-adjusted litters (12 pups/L) were randomly divided into three groups-control, RSV, and NR-which, from postnatal days 2 to 20, were given daily, with the aid of a pipette, an oral dose of 10-15 µL of vehicle (water), a RSV solution (Sigma-Aldrich, St. Louis, MI, USA, R5010), or a NR solution (Chemical Point, Oberhaching, Germany, CP1341-23-7-BULK), respectively. RSV was used at a dose of 2 mg/kg body weight, and NR, at a dose equivalent to~15-fold the total vitamin B3 ingested daily from maternal milk [6]. Male animals were weaned on a standard chow diet (3.3 kcal/g, 8% calories from fat; Panlab, A04) on day 21 of age, and habituated to a purified normal-fat diet (NFD, 10% energy as fat; Research Diets, D12450J) from day 75 to day 90.…”

“…Neonatal treatment with either RSV or NR results in an up-regulated expression of the beige adipocyte-selective marker Slc27a1 in iWAT in adulthood in the male progeny [6]. Slc27a1 up-regulation is especially evident under NFD conditions in the RSV mice (3.2-fold induction under NFD vs. 1.45-fold induction under HFD, relative to levels in corresponding controls), and under HFD conditions in the NR mice (2-fold induction vs. 1.15-fold induction under NFD) [6].…”

“…The early postnatal period might be particularly important for this programming since it is a time-window of active WAT development [5]. We previously showed that mild supplementation during the suckling period with the polyphenol resveratrol (RSV, 3,5,4 -trihydroxy-trans-stilbene) or the B3 vitamin nicotinamide riboside (NR) promotes in mice the appearance of browning-related features in subcutaneous WAT in adulthood, together with better responses to a high-fat diet, selectively in the male progeny [6]. In good concordance, RSV supplementation of the maternal high-fat diet promotes brown and beige adipocyte development and prevents programmed obesity in the male offspring [7].…”

“…Slc27a1 (solute carrier family 27 member 1) and Prdm16 (PR domain containing 16) are two browning-related genes that are induced in WAT of male mice treated neonatally with RSV or NR and derived primary cultures [6,8]. The protein product of Slc27a1 is fatty acid transport protein 1 (FATP1), an integral membrane protein that mediates the cellular uptake of long-chain fatty acids and can channel the uptaken fatty acids toward oxidation in mitochondria [9].…”