title: Divergent effects of a CLA-enriched beef diet on metabolic health in ApoE-/- and ob/ob mice.
abstract: 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.
authors.affiliation: School of Public Health, Physiotherapy and Population Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Clare M
authors.initials: CM
authors.lastname: Reynolds
authors.forename: Sinead
authors.initials: S
authors.lastname: Toomey
authors.forename: Rachael
authors.initials: R
authors.lastname: McBride
authors.forename: Jolene
authors.initials: J
authors.lastname: McMonagle
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Morine
authors.forename: Orina
authors.initials: O
authors.lastname: Belton
authors.forename: Aidan P
authors.initials: AP
authors.lastname: Moloney
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000378:metabolism*; D002417:Cattle; D004032:Diet; D004195:Disease Models, Animal; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000235:genetics; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008461:Meat Products / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese
chemical_list: D001057:Apolipoproteins E; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D020738:Leptin; D044243:Linoleic Acids, Conjugated; D008055:Lipids; C503589:cis-9, trans-11-conjugated linoleic acid; C046938:9,11-linoleic acid; D005947:Glucose