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

Chang Yeop Han, Atil Kargi, Mohamed Omer, Christina K. Chan, Martin Wabitsch, Kevin D. O'Brien, Thomas N. Wight, Alan Chait

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE - 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. RESEARCH DESIGN AND METHODS - Differentiated 3T3-L1, Simpson-Golabi-Behmel syndrome adipocytes, and mouse embryonic fibroblasts were exposed to various FFAs (250 μmol/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) κB 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 NFκB 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 NFκB translocation stimulated by both excess glucose and palmitate via a peroxisome prolifterator-activated receptor (PPAR) γ-dependent pathway. CONCLUSIONS - Excess glucose and SFAs regulate chemotactic factor expression by a mechanism that involves ROS generation, NFκB, and PPARγ, and which is repressed by PUFAs. Certain SFAs, but not excess glucose, trigger chemotactic factor expression via a TLR4-dependent pathway. 2010

Original languageEnglish
Pages (from-to)386-396
Number of pages11
JournalDiabetes
Volume59
Issue number2
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

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Chemotactic Factors
Unsaturated Fatty Acids
Nonesterified Fatty Acids
Adipocytes
Hypertrophy
Monocytes
Serum Amyloid A Protein
Inflammation
Glucose
Chemokine CCL2
Palmitates
Hyaluronic Acid
Fatty Acids
Reactive Oxygen Species
Toll-Like Receptor 4
Peroxisomes
Triglycerides
Laurates
Myristic Acid
Linoleic Acid

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / Han, Chang Yeop; Kargi, Atil; Omer, Mohamed; Chan, Christina K.; Wabitsch, Martin; O'Brien, Kevin D.; Wight, Thomas N.; Chait, Alan.

In: Diabetes, Vol. 59, No. 2, 01.02.2010, p. 386-396.

Research output: Contribution to journalArticle

Han, Chang Yeop ; Kargi, Atil ; Omer, Mohamed ; Chan, Christina K. ; Wabitsch, Martin ; O'Brien, Kevin D. ; Wight, Thomas N. ; Chait, Alan. / 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. In: Diabetes. 2010 ; Vol. 59, No. 2. pp. 386-396.
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T1 - Differential effect of saturated and unsaturated free fatty acids on the generation of monocyte adhesion and chemotactic factors by adipocytes

T2 - Dissociation of adipocyte hypertrophy from inflammation

AU - Han, Chang Yeop

AU - Kargi, Atil

AU - Omer, Mohamed

AU - Chan, Christina K.

AU - Wabitsch, Martin

AU - O'Brien, Kevin D.

AU - Wight, Thomas N.

AU - Chait, Alan

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N2 - OBJECTIVE - 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. RESEARCH DESIGN AND METHODS - Differentiated 3T3-L1, Simpson-Golabi-Behmel syndrome adipocytes, and mouse embryonic fibroblasts were exposed to various FFAs (250 μmol/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) κB 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 NFκB 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 NFκB translocation stimulated by both excess glucose and palmitate via a peroxisome prolifterator-activated receptor (PPAR) γ-dependent pathway. CONCLUSIONS - Excess glucose and SFAs regulate chemotactic factor expression by a mechanism that involves ROS generation, NFκB, and PPARγ, and which is repressed by PUFAs. Certain SFAs, but not excess glucose, trigger chemotactic factor expression via a TLR4-dependent pathway. 2010

AB - OBJECTIVE - 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. RESEARCH DESIGN AND METHODS - Differentiated 3T3-L1, Simpson-Golabi-Behmel syndrome adipocytes, and mouse embryonic fibroblasts were exposed to various FFAs (250 μmol/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) κB 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 NFκB 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 NFκB translocation stimulated by both excess glucose and palmitate via a peroxisome prolifterator-activated receptor (PPAR) γ-dependent pathway. CONCLUSIONS - Excess glucose and SFAs regulate chemotactic factor expression by a mechanism that involves ROS generation, NFκB, and PPARγ, and which is repressed by PUFAs. Certain SFAs, but not excess glucose, trigger chemotactic factor expression via a TLR4-dependent pathway. 2010

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