The role of visceral and subcutaneous adipose tissue fatty acid composition in liver pathophysiology associated with NAFLD

Abstract

Visceral adiposity is associated with type-2-diabetes, inflammation, dyslipidemia and non-alcoholic fatty liver disease (NAFLD), whereas subcutaneous adiposity is not. We hypothesized that the link between visceral adiposity and liver pathophysiology involves inherent or diet-derived differences between visceral and subcutaneous adipose tissue to store and mobilize saturated fatty acids. The goal of the present study was to characterize the fatty acid composition of adipose tissue triglyceride and portal vein fatty acids in relation to indices of liver dysregulation. For 8 weeks rats had free access to control (CON; 12.9% corn/safflower oil; 3.6 Kcal/g), high saturated fat (SAT; 45.2% cocoa butter; 4.5 Kcal/g) or high polyunsaturated fat (PUFA; 45.2% safflower oil; 4.5 Kcal/g) diets. Outcome measures included glucose tolerance, visceral and subcutaneous adipose tissue triglyceride, liver phospholipids and plasma (portal and systemic) free fatty acid composition, indices of inflammation and endoplasmic reticulum stress in the liver and adipose tissue depots and circulating adipo/cytokines. Hepatic triglycerides were significantly increased in both high fat diet groups compared to control and were significantly higher in PUFA compared to SAT. Although glucose tolerance was not different among diet groups, SAT increased markers of inflammation and ER stress in the liver and both adipose tissue depots. Fatty acid composition did not differ among adipose depots or portal blood in any dietary group. Overall, these data suggest that diets enriched in saturated fatty acids are associated with liver inflammation, ER stress and injury, but that any link between visceral adipose tissue and these liver indices does not involve selective changes to fatty acid composition in this depot or the portal vein.

Keywords: adipose tissue distribution; dyslipidemia; fatty liver; metabolic syndrome; obesity; saturated fat.

Figure 1.

Subcutaneous and visceral adipose tissue percent fatty acid composition of palmitic (16:0) (A), stearic (18:0) (B), oleic (18:1n9) (C) and linoleic (18:2) acid (D). 18:0 was higher in the subcutaneous and visceral adipose depot of the SAT group compared with CON and PUFA. 18:1n9 was also higher in the SAT group. 18:2 was higher in PUFA compared with CON and SAT. (Unlike letters indicate significance; P ≤ 0.05).

Figure 2.

Systemic and portal blood percent fatty acid composition of myristic (14:0) (A), palmitic (16:0) (B), stearic (18:0) (C), palmitoleic (16:1) (D), oleic (18:1n9) (E), linoleic (18:2) (F), and arachidonic acid (20:4) (G). In the SAT group 18:0 and 18:1n-9 were higher whereas 18:2 and 20:4 were lower compared with CON and PUFA. 18:2 was highest in the PUFA group. 14:0 was lower in blood collected from the portal vein compared with systemic blood while 18:1n9 and linoleic acid 18:2 higher the portal vein blood. (Unlike letters indicate significance; P ≤ 0.05).

Figure 3.

Percent fatty acid composition of liver phospholipids. Stearic (18:0) and oleic acid (18:1n9) were higher and linoleic acid (18:2) lower in SAT compared with CON and PUFA. (Unlike letters indicate significance; P ≤ 0.05).

Figure 4.

Plasma alanine aminotransferase concentration was higher in SAT compared with CON and PUFA. (Unlike letters indicate significance; P ≤ 0.05).

Figure 5.

Gene expression of factors involved in liver injury and ER stress. Expression of gene markers of liver fibrosis, α-smooth muscle actin (SMA/Acta2) (A), transforming growth factor-β (Tgfb1) (B), and collagen-α1 (Col1a1) mRNA (C), were higher in SAT compared with CON and PUFA. ER stress markers, spliced X box binding protein-1 (XBP1s), glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and growth arrest and DNA damage inducible protein 34 (GADD34) were also higher in SAT compared with CON and PUFA. (Unlike letters indicate significance; P ≤ 0.05).

Figure 6.

Gene expression of factors involved in subcutaneous and visceral adipose tissue inflammation and ER stress. C-type lectin domain family 7 member A (Clec7a) and monocyte chemoattractant protein 1 (MCP-1) were higher in visceral compared with subcutaneous adipose tissue (A-B). SAT further increased Clec7a and MCP-1 gene expression in visceral adipose tissue only compared with CON and PUFA. Interleukin 10 (IL10) and spliced X box binding protein-1 (XBP1s) mRNA were higher in subcutaneous compared with visceral adipose tissue (C–D) and SAT further increased IL10 and XBP1s gene expression in the subcutaneous depot only Tumor necrosis factors α (TNFα) and interleukin 6 (IL6) were increased in SAT groups compared with CON, but there were no depot differences (E-F). (Unlike letters indicate significance; P ≤ 0.05).

Figure 7.

Portal and systemic plasma insulin and adipo/cytokine concentration. PUFA significantly increased portal vein insulin concentration compared with CON and SAT (A). MCP-1 was significantly higher in portal circulation than systemic (B) and PAI was significantly higher in SAT and PUFA than CON (C). (Unlike letters indicate significance; P ≤ 0.05).