DHA Reduces Monocyte Inflammatory Signalling and NF-kappaB Activation in White Adipose Tissue
RESEARCH DESIGN AND METHODS: Differentiated 3T3-L1, Simpson-Golabi-Behmel syndrome adipocytes, and mouse embryonic fibroblasts were exposed to various FFAs (250 micromol/l) in either 5 or 25 mmol/l (high) glucose for evaluation of SAA, MCP-1, and HA regulation in vitro. RESULTS: Saturated fatty acids (SFAs) such as laurate, myristate, and palmitate increased cellular triglyceride accumulation, SAA, and MCP-1 expression; generated reactive oxygen species (ROS), and increased nuclear factor (NF) kappaB translocation in both 5 and 25 mmol/l glucose. Conversely, polyunsaturated fatty acids (PUFAs) such as arachidonate, eicosapentaenate, and docosahexaenate (DHA) decreased these events. Gene expression could be dissociated from triglyceride accumulation. Although excess glucose increased HA content, SFAs, oleate, and linoleate did not. Antioxidant treatment repressed glucose- and palmitate-stimulated ROS generation and NFkappaB translocation and decreased SAA and MCP-1 expression and monocyte chemotaxis. Silencing toll-like receptor-4 (TLR4) markedly reduced SAA and MCP-1 expression in response to palmitate but not glucose. DHA suppressed NFkappaB translocation stimulated by both excess glucose and palmitate via a peroxisome prolifterator-activated receptor (PPAR) gamma-dependent pathway.
CONCLUSIONS: Excess glucose and SFAs regulate chemotactic factor expression by a mechanism that involves ROS generation, NFkappaB, and PPARgamma, and which is repressed by PUFAs. Certain SFAs, but not excess glucose, trigger chemotactic factor expression via a TLR4-dependent pathway.
Yeop Han C, Kargi AY, Omer M, Chan CK, Wabitsch M, O'Brien KD, Wight TN, Chait A.
Differential effect of saturated and unsaturated free fatty acids on the generation of monocyte adhesion and chemotactic factors by adipocytes: dissociation of adipocyte hypertrophy from inflammation.
Department of Medicine, University of Washington, Seattle, Washington, USA.