Fatty acid-mediated endoplasmic reticulum stress in vivo: differential response to the infusion of Soybean and Lard Oil in rats

Abstract

Background: In cell systems, saturated fatty acids, compared to unsaturated fatty acids, induce a greater degree of ER stress and inflammatory signaling in a number of cell types, including hepatocytes and adipocytes. The aim of the present study was to determine the effects of infusions of lard oil (enriched in saturated fatty acids) and soybean oil (enriched in unsaturated fatty acids) on liver and adipose tissue ER stress and inflammatory signaling in vivo.

Methods: Lipid emulsions containing glycerol, phosphatidylcholine, antibiotics (Control, n=7) and either soybean oil (Soybean, n=7) or lard oil (Lard, n=7) were infused intravenously into rats over a 4 h period.

Results: Plasma free fatty acid levels were 0.5±0.1 mmol/L (mean±SD) in Control and were increased to 1.0±0.3 mmol/L and 1.1±0.3 mmol/L in Soybean and Lard, respectively. Glucose and insulin levels were not different among groups. Markers of endoplasmic reticulum (ER) stress and activation of inflammatory pathway signaling were increased in liver and adipose tissue from Soybean and Lard compared to Control, but were increased to a greater extent in Lard compared to Soybean.

Conclusions: These data suggest that elevated plasma free fatty acids can induce hepatic and adipose tissue ER stress and inflammation in vivo. In addition, saturated fatty acids appear to be more cytotoxic than unsaturated fatty acids in vivo.

Figure 1

Plasma glucose, free fatty acid (FFA) and insulin concentrations during control (n=7), soybean oil (n=7) and lard oil (n=7) infusions. *, significantly different from Control.

Figure 2

ER stress and inflammatory signaling in the liver. Phosphorylation of PERK and eIF2α (A), XBP1 splicing (B), Chop, GADD34 and GRP78 gene expression (C) and phosphorylation of IKKB (D) in the liver following control (n=7), soybean oil (n=7) or lard oil (n=7) infusions. *, significantly different from Control; +, significantly different from other two groups.

Figure 3

Inflammatory gene expression in the liver. Interleukin-1β (IL-1B), macrophage inflammatory protein-1α (MIP-1a) tumor necrosis factor-α (TNFa), matrix metalloproteinase 12 (Mmp12), and CD68 antigen (CD68) mRNA following Control (n=7), Soybean oil (n=7) or Lard oil(n=7) infusions. *, significantly different from Control; +, significantly different from other two groups.

Figure 4

ER stress and inflammatory signaling in adipose tissue. Phosphorylation of PERK and eIF2α (A), XBP1 splicing (B), Chop, GADD34 and GRP78 gene expression (C) and phosphorylation of IKKB (D) in adipose tissue following Control (n=7), Soybean oil (n=7) or Lard oil (n=7) infusions. *, significantly different from Control; +, significantly different from other two groups.

Figure 5

Inflammatory gene expression in adipose tissue. Interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNFa), suppressor of cytokine signaling-3 (SOC-3) and haptoglobin mRNA following Control (n=7), Soybean oil (n=7)or Lard oil (n=7) infusions. *, significantly different from Control; +, significantly different from other two groups.