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

• Published in: Diabetes (New York, N.Y.) Vol. 59; no. 2; pp. 386 - 396
• Main Authors: CHANG YEOP HAN, KARGI, Atil Y, OMER, Mohamed, CHAN, Christina K, WABITSCH, Martin, O'BRIEN, Kevin D, WIGHT, Thomas N, CHAIT, Alan
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2010
• Subjects: 3T3 Cells - cytology; 3T3 Cells - drug effects; 3T3 Cells - physiology; Adipocytes; Adipocytes - drug effects; Adipocytes - pathology; Adipocytes - physiology; Adipose tissue; Adipose Tissue - cytology; Adipose Tissue - drug effects; Adipose Tissue - physiology; Adipose Tissue - physiopathology; Adipose tissues; Animals; Biological and medical sciences; Body fat; Cell Adhesion - physiology; Cell Differentiation; Chemotaxis - physiology; Diabetes; Diabetes. Impaired glucose tolerance; Embryo, Mammalian - cytology; Embryo, Mammalian - physiology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fat cells; Fatty acids; Fatty Acids - pharmacology; Fatty Acids, Unsaturated - pharmacology; Fibroblasts; Flow Cytometry; Gene expression; Gene Silencing; Glucose; Humans; Hyaluronic acid; Hypertrophy; Inflammation - physiopathology; Insulin resistance; Medical sciences; Mice; Mice, Inbred C57BL; Monocytes; Monocytes - drug effects; Monocytes - physiology; Obesity; Original; Physiological aspects; Reactive Oxygen Species - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Serum Amyloid A Protein - genetics; Toll-Like Receptor 4 - genetics; Endocrinopathy; Adipocyte; Monocyte; Diabetes mellitus; Lipids; Inflammation; Free fatty acid; Adhesion; Hypertrophy
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db09-0925

Obesity is associated with monocyte-macrophage accumulation in adipose tissue. Previously, we showed that glucose-stimulated production by adipocytes of serum amyloid A (SAA), monocyte chemoattractant protein (MCP)-1, and hyaluronan (HA) facilitated monocyte accumulation. The current objective was to determine how the other major nutrient, free fatty acids (FFAs), affects these molecules and monocyte recruitment by adipocytes. 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. 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. 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.