Divergent effects of a CLA-enriched beef diet on metabolic health in ApoE−/− and ob/ob mice

• Published in: The Journal of nutritional biochemistry 2013-02, Vol.24 (2), p.401-411
• Main Authors: Reynolds, Clare M, Toomey, Sinead, McBride, Rachael, McMonagle, Jolene, Morine, Melissa J, Belton, Orina, Moloney, Aidan P, Roche, Helen M
• Format: Article
• Language: English
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; ApoE; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - metabolism; beef; blood glucose; blood lipids; Cattle; Conjugated linoleic acid; dairy products; Diet; Disease Models, Animal; Fatty Acids, Unsaturated - biosynthesis; functional foods; Gene Expression Profiling; Gene Expression Regulation - drug effects; genes; glucose; Glucose - metabolism; homeostasis; insulin; Insulin - metabolism; insulin resistance; isomers; Leptin - genetics; Linoleic Acids, Conjugated - pharmacology; Lipids - blood; Liver - drug effects; Liver - metabolism; Meat Products - adverse effects; Metabolic syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; ob/ob; transcriptomics
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2011.12.006

Conjugated linoleic acid (CLA) is found naturally in meat and dairy products, and represents a potential therapeutic functional nutrient. However, given the discrepancies in isomer composition and concentration, controversy surrounds its proposed antidiabetic, antiobesity effects. This study focused on the effects of CLA-enriched beef (composed predominantly of c9, t11-CLA) in two separate models of metabolic disease: proatherosclerotic ApoE⁻/⁻ mice and diabetic, leptin-deficient ob/ob mice. Animals were fed CLA-enriched beef for 28 days, and markers of the metabolic syndrome and atherosclerosis were assessed. Comprehensive hepatic transcriptomic analysis was completed to understand divergent metabolic effects of CLA. CLA-enriched beef significantly reduced plasma glucose, insulin, nonesterified fatty acid and triacylglycerol and increased adiponectin levels in ob/ob mice. In contrast, plasma lipid profiles and glucose homeostasis deteriorated and promoted atherosclerosis following the CLA-enriched beef diet in ApoE⁻/⁻ mice. Hepatic transcriptomic profiling revealed divergent effects of CLA-enriched beef on insulin signaling and lipogenic pathways, which were adversely affected in ApoE⁻/⁻ mice. This study demonstrated clear divergence in the effects of CLA. CLA-enriched beef improved metabolic flexibility in ob/ob mice, resulting in enhanced insulin sensitivity. However, CLA-enriched diet increased expression of lipogenic genes, resulting in inefficient fatty acid storage which increases lipotoxicity in peripheral organs, and led to profound metabolic dysfunction in ApoE⁻/⁻ mice. While CLA may have potential health effects, in some circumstances, caution must be exercised in presenting this bioactive lipid as a potential functional food for the treatment of metabolic disease.