Nicotinamide Promotes Adipogenesis in Umbilical Cord-Derived Mesenchymal Stem Cells and Is Associated with Neonatal Adiposity: The Healthy Start BabyBUMP Project

PLoS One. 2016 Jul 14;11(7):e0159575. doi: 10.1371/journal.pone.0159575. eCollection 2016.

Abstract

The cellular mechanisms whereby excess maternal nutrition during pregnancy increases adiposity of the offspring are not well understood. However, nicotinamide (NAM), a fundamental micronutrient that is important in energy metabolism, has been shown to regulate adipogenesis through inhibition of SIRT1. Here we tested three novel hypotheses: 1) NAM increases the adipogenic response of human umbilical cord tissue-derived mesenchymal stem cells (MSCs) through a SIRT1 and PPARγ pathway; 2) lipid potentiates the NAM-enhanced adipogenic response; and 3) the adipogenic response to NAM is associated with increased percent fat mass (%FM) among neonates. MSCs were derived from the umbilical cord of 46 neonates born to non-obese mothers enrolled in the Healthy Start study. Neonatal %FM was measured using air displacement plethysmography (Pea Pod) shortly after birth. Adipogenic differentiation was induced for 21 days in the 46 MSC sets under four conditions, +NAM (3mM)/-lipid (200 μM oleate/palmitate mix), +NAM/+lipid, -NAM/+lipid, and vehicle-control (-NAM/-lipid). Cells incubated in the presence of NAM had significantly higher PPARγ protein (+24%, p <0.01), FABP4 protein (+57%, p <0.01), and intracellular lipid content (+51%, p <0.01). Lipid did not significantly increase either PPARγ protein (p = 0.98) or FABP4 protein content (p = 0.82). There was no evidence of an interaction between NAM and lipid on adipogenic response of PPARγ or FABP4 protein (p = 0.99 and p = 0.09). In a subset of 9 MSC, SIRT1 activity was measured in the +NAM/-lipid and vehicle control conditions. SIRT1 enzymatic activity was significantly lower (-70%, p <0.05) in the +NAM/-lipid condition than in vehicle-control. In a linear model with neonatal %FM as the outcome, the percent increase in PPARγ protein in the +NAM/-lipid condition compared to vehicle-control was a significant predictor (β = 0.04, 95% CI 0.01-0.06, p <0.001). These are the first data to support that chronic NAM exposure potentiates adipogenesis in human MSCs in-vitro, and that this process involves PPARγ and SIRT1.

MeSH terms

  • Adipogenesis / drug effects*
  • Adiposity / drug effects*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Infant, Newborn / metabolism
  • Mesenchymal Stem Cells / drug effects*
  • Niacinamide / pharmacology*
  • PPAR gamma / metabolism
  • Plethysmography
  • Polymerase Chain Reaction
  • Sirtuin 1 / metabolism
  • Umbilical Cord / cytology
  • Umbilical Cord / drug effects*

Substances

  • PPAR gamma
  • Niacinamide
  • SIRT1 protein, human
  • Sirtuin 1