The intestinal bioavailability of vaccenic acid and activation of peroxisome proliferator-activated receptor-α and -γ in a rodent model of dyslipidemia and the metabolic syndrome.

Abstract

SCOPE:

Evidence suggests a neutral to beneficial role of certain trans fatty acids (TFA) from natural ruminant sources. Trans11-18:1 (vaccenic acid, VA), the most predominant ruminant TFA and a precursor to conjugated linoleic acid, has been shown to improve atherogenic dyslipidemia and symptoms of hepatic steatosis in animal models. The objective of this study was to assess the intestinal bioavailability of various VA sources including synthetic free fatty acid (FFA) and natural ruminant triglyceride forms, as well as the mechanistic pathways that mediate VA's bioactivity.

METHODS AND RESULTS:

VA acts as a partial agonist to both peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ in vitro, with similar affinity compared to commonly known PPAR agonists. It was further confirmed that VA at 30 and 100 μM concentrations suppressed cardiomyocyte hypertrophy vitro in a PPAR-α- and PPAR-γ-dependent manner. In vivo, feeding of VA (1%, w/w) resulted in increased mRNA and protein expression of PPAR-γ in the mucosa of JCR:LA-cp rats, a model of the metabolic syndrome (p < 0.01 and p < 0.05, respectively) compared to control. In addition, VA from a triglyceride source had greater intestinal bioavailability in vivo compared to VA provided in an FFA form (p < 0.01).

CONCLUSION:

The activation of PPAR-α- and PPAR-γ-dependent pathways provides a mechanistic explanation of how VA improves blood lipids and related metabolic disorders during conditions of hyperlipidemia. This report also supports the consideration of differential reporting of industrially produced versus natural TFA on food nutrient labels.

• Authors: Ye Wang, Maria M Jacome-Sosa, Megan R Ruth, Yan Lu, Jianheng Shen, Martin J Reaney, Shannon L Scott, Michael E R Dugan, Hope D Anderson, Catherine J Field, Spencer D Proctor, Donna F Vine
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 56 Issue 8 Pg. 1234-46 (Aug 2012) ISSN: 1613-4133 [Electronic] Germany
• PMID: 22714958 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Fatty Acids
• Oleic Acids
• PPAR alpha
• PPAR gamma
• 11-octadecenoic acid

Topics

• Animals
• Binding Sites
• Binding, Competitive
• Disease Models, Animal
• Dyslipidemias (drug therapy, metabolism)
• Fatty Acids (analysis)
• Gene Expression Regulation
• Intestinal Absorption
• Intestinal Mucosa
• Lipid Metabolism (genetics)
• Liver (drug effects, metabolism)
• Male
• Mesentery (chemistry)
• Metabolic Syndrome (drug therapy, metabolism)
• Myocytes, Cardiac (drug effects, pathology)
• Oleic Acids (pharmacokinetics)
• PPAR alpha (genetics, metabolism)
• PPAR gamma (genetics, metabolism)
• Rats
• Rats, Inbred Strains