Divergent Response of Murine and Porcine Adipocytes to Stimulation of Browning Genes by 18-Carbon Polyunsaturated Fatty Acids and Beta-Receptor Agonists

Long-chain fatty acids (LCFA) are known to activate brown and beige adipocytes. However, very little is known about the effects of the number and the position of double bonds in LCFA with the same length on brown fat-specific gene expression. To determine the specificity of LCFA in the regulation of these genes in different adipocyte models, fully differentiated 10T1/2, 3T3-L1, murine, or porcine primary adipocytes (obtained from the subcutaneous fat pad of C57BL/6 mice or Landrace x Yorkshire x Duroc crossbred piglets) were treated with 50M of the following 18-carbon fatty acids: stearic acid (STA; 18:0), oleic acid (OLA; 18:1, 9), linoleic acid (LNA; 18:2, 9,12), -linolenic acid (ALA; 18:3, 9,12,15), -linolenic acid (GLA; 18:3, 6,9,12), or pinolenic acid (PLA; 18:3, 5,9,12) for 24h with or without 4-h norepinephrine (NE) treatment. Expression levels of thermoregulatory markers were measured by quantitative real-time PCR. LNA, ALA, GLA, and PLA upregulated Ucp1 expression and tended to upregulate Pgc1a expression in murine primary adipocytes, but not in 10T1/2, 3T3-L1, and porcine primary adipocytes. In murine primary adipocytes, NE induced a higher expression of Ucp1 and Pgc1a than non-NE-treated cells, and PLA augmented the NE effect. In 10T1/2 cells, NE upregulated Ucp1 and Pgc1a expression, but there was no fatty acid effect. However, 3T3-L1 cells were insensitive to both fatty acid and beta-adrenergic agonist stimulation. These results indicate that different adipocyte cell types have different levels of sensitivity to both LCFA and beta agonists in regard to induction of brown fat-specific gene expression.