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

Abstract

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 × Yorkshire × Duroc crossbred piglets) were treated with 50 μM of the following 18-carbon fatty acids: stearic acid (STA; 18:0), oleic acid (OLA; 18:1, Δ9), linoleic acid (LNA; 18:2, Δ9,12), α-linolenic acid (ALA; 18:3, Δ9,12,15), γ-linolenic acid (GLA; 18:3, Δ6,9,12), or pinolenic acid (PLA; 18:3, Δ5,9,12) for 24 h 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.

Lipopolysaccharide Alters Thermogenic and Inflammatory Genes in White Adipose Tissue in Mice Fed Diets with Distinct 18‐Carbon Fatty‐Acid Composition

“…To determine the effects of individual 18‐carbon fatty acids on response to LPS and NE, a nonselective β‐adrenergic receptor agonist, on day 6 of differentiation, fully differentiated adipocytes were pretreated for 24 h with 1 μg/mL of BSA or 50 μM of BSA‐bound 18‐carbon fatty acids: stearic acid (STA; 18:0), oleic acid (OLA; 18:1, Δ9), linoleic acid (LNA; 18:2, Δ9,12), and α‐linolenic acid (ALA; 18:3, Δ9,12,15). The fatty acids were free from heavy metals and of the purest grade (≥98% purity; Cayman, Ann Arbor, MI, USA), and prepared as previously described (Shin and Ajuwon, ). This was followed by treatment with 100 ng/mL of LPS for 6 h, by treatment with 10 μM of NE (a nonselective β‐adrenergic receptor agonist; Cayman Chemical, Ann Arbor, MI, USA) for 4 h, or by pretreatment with 100 ng/mL of LPS for 2 h and 10 μM of NE for another 4 h.…”

Transdifferentiation of bovine epithelial cells towards adipocytes in the presence of myoepithelium

“…Our results provide the evidence that luminal epithelial cells under adipogenic inducers, such as LA, TZD's [14,15] can transdifferentiate to the adipocytes, however the PPARγ inhibition restricted the adipogenesis conversion in luminal epithelial cells. The TZD+LA treatment in luminal cells induced the PPARγ pathway that initiates the process of adipogenesis through lipid accumulation, which will be backed up by the terminal differentiator C/EBPα [16,17].…”

Rosiglitazone-induced changes in the oxidative stress metabolism and fatty acid composition in relation with trace element status in the primary adipocytes

“…Eicosapentaenoic acid is a PUFA which enhances insulin sensitivity and thermogenesis (42). On the other hand, 18-carbon fatty acids including stearic and oleic acid were reported as metabolic modifiers via in vivo studies since they increase the thermogenic capacity of WAT (43,44). The relative content of both stearic acid and oleic acid increased in RSG-treated cells compared to the control according to our data that may show the contribution of RSG to the conversion of WAT into BAT ( Figure 5).…”