Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis.
A combined histological and microarray analysis of the white adipose tissue (WAT) of mice fed trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) was performed to better define functional responses. Mice fed t10c12 CLA for 14 days lost 85% of WAT mass, 95% of adipocyte lipid droplet volume, and 15 or 47% of the number of adipocytes and total cells, respectively. Microarray profiling of replicated pools (n = 2 per day x diet) of control and treated mice (n = 140) at seven time points after 1-17 days of t10c12 CLA feeding found between 2,682 and 4,216 transcript levels changed by twofold or more. Transcript levels for genes involved in glucose and fatty acid import or biosynthesis were significantly reduced. Highly expressed transcripts for lipases were significantly reduced but still abundant. Increased levels of mRNAs for two key thermogenesis proteins, uncoupling protein 1 and carnitine palmitoyltransferase 1, may have increased energy expenditures. Significant reductions of mRNAs for major adipocyte regulatory factors, including peroxisome proliferator activated receptor-gamma, sterol regulatory binding protein 1, CAAT/enhancer binding protein-alpha, and lipin 1 were correlated with the reduced transcript levels for key metabolic pathways in the WAT. A prolific inflammation response was indicated by the 2- to 100-fold induction of many cytokine transcripts, including those for IL-6, IL-1beta, TNF ligands, and CXC family members, and an increased density of macrophages. The mRNA changes suggest that a combination of cell loss, increased energy expenditure, and residual transport of lipids out of the adipocytes may account for the cumulative mass loss observed.
LaRosa
P Christopher
PC
Center for Biotechnology, University of Nebraska, Lincoln, Nebraska, USA.
Miner
Jess
J
Xia
Yuannan
Y
Zhou
You
Y
Kachman
Steve
S
Fromm
Michael E
ME
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000033:anatomy & histology / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002452:Cell Count; D004041:Dietary Fats / Q000008:administration & dosage*; D015536:Down-Regulation; D004734:Energy Metabolism; D007249:Inflammation; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage* / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000235:genetics; D010711:Phosphatidate Phosphatase; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics
D022763:CCAAT-Enhancer-Binding Protein-alpha; D004041:Dietary Fats; D044243:Linoleic Acids, Conjugated; D009687:Nuclear Proteins; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase