Acute effects of dietary fatty acids on osteclastogenesis via RANKL/RANK/OPG system

Mol Nutr Food Res. 2016 Nov;60(11):2505-2513. doi: 10.1002/mnfr.201600303. Epub 2016 Jul 27.

Abstract

Scope: Postprandial state is directly linked with chronic diseases. We hypothesized that dietary fats may have acute effects on health status by modulating osteoclast differentiation and activation in a fatty acid-dependent manner.

Methods and results: In healthy subjects, a fat-enriched meal increased plasma levels of the RANKL (receptor activator of nuclear factor κB ligand)/OPG (osteoprotegerin) ratio (SFAs > MUFAs = PUFAs) in the postprandial state. Postprandial TRL-SFAs enhanced tartrate-resistant acid phosphatase (TRAP) activity and the expression of osteoclast marker genes (TRAP, OSCAR, RANK, and CATHK) while downregulated the expression of OPG gene in human monocyte-derived osteoclasts. These effects were not observed with monounsaturated fatty acid (MUFA)-enriched postprandial triglyceride-rich lipoproteins (TRLs). Moreover, postprandial TRL-SFAs increased the release of osteoclastogenic cytokines (TNF-α, IL-1β, and IL-6) meanwhile TRL-MUFAs and TRL-PUFAs increased the release of anti-osteoclastogenic cytokines (IL-4 and IL-10) in the medium of human monocyte-derived osteoclasts.

Conclusion: For the first time, we show that postprandial TRLs are metabolic entities with osteoclastogenic activity and that this property is related to the type of dietary fatty acid in the meal. The osteoclastogenic potency was as follows: SFAs >>> MUFAs = PUFAs. These exciting findings open opportunities for developing nutritional strategies with olive oil as the principal dietary source of MUFAs, notably oleic acid, to prevent development and progression of osteoclast-related diseases.

Keywords: Osteoclast; Osteoprotegerin; Postprandial state; RANKL; Triglyceride-rich lipoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diet
  • Dietary Fats / pharmacology*
  • Fatty Acids / metabolism
  • Fatty Acids, Monounsaturated / analysis
  • Fatty Acids, Monounsaturated / pharmacology
  • Fatty Acids, Unsaturated / pharmacology
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-6 / metabolism
  • Lipoproteins
  • Male
  • Meals
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism*
  • Osteoprotegerin / metabolism
  • Plant Oils / pharmacology
  • Postprandial Period / drug effects
  • RANK Ligand* / blood
  • RANK Ligand* / metabolism
  • RANK Ligand* / pharmacology
  • Triglycerides
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Dietary Fats
  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • Fatty Acids, Unsaturated
  • Interleukin-6
  • Lipoproteins
  • Osteoprotegerin
  • Plant Oils
  • RANK Ligand
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • lipoprotein triglyceride
  • Interleukin-10
  • Interleukin-4