Conjugated linoleic acid (CLA) promotes inflammation to a greater extent in human adipocytes compared to preadipocytes

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Kristina Martinez (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Michael McIntosh

Abstract: Due to the increasing prevalence of obesity and diabetes among children and adults worldwide, it is imperative to identify dietary strategies that promote weight control. One potential anti-obesity compound is conjugated linoleic acid (CLA), sold worldwide for weight loss. However, the safety and efficacy of this supplement remains questionable. Current research shows that, in addition to reducing fat mass, trans-10,cis-12 (10,12) CLA supplementation in animals and some humans leads to insulin resistance, hyperlipidemia, or fatty liver. In vitro studies suggest that 10,12 CLA causes inflammation in primary cultures of human adipocytes by increasing mitogen activated extracellular kinase/extracellular signal-related kinase (MEK/ERK) and nuclear factor kappa B (NFêB) signaling, which impairs glucose and fatty acid uptake and utilization. However, the link between inflammatory signaling in primary cultures of human adipocytes and CLA-mediated delipidation has not been fully characterized. Additionally, the particular cell type (i.e., preadipoyctes vs. adipocytes) responsible for 10,12 CLA-mediated inflammation and insulin resistance in white adipose tissue is unknown. Therefore, the objective of this work was to determine the cell type responsible for 10,12 CLA-mediated inflammation and insulin resistance in cultures of newly differentiated human adipocytes (Aim 1), and to identify the specific upstream mechanisms involved (Aim 2). To examine Aim 1, inflammatory gene expression and protein secretion, prostaglandin secretion, or mitogen-activated protein kinase (MAPK) and cJun phosphorylation was measured in adipocytes vs. preadipocytes in four distinct cell culture models. To examine Aim 2, chemical inhibitors were employed to determine the role of protein kinases, including the MAPK cJun N-terminal kinase (JNK) and diacylglycerol kinases (DGKs) in 10,12 CLA-mediated inflammatory signaling and insulin resistance in newly differentiated primary human adipocytes. Collectively, results from this project reveal that 10,12 CLA instigates release of inflammatory signals from adipocytes that subsequently activate adjacent preadipocytes. Mechanisms of 10,12 CLA-mediated inflammatory signaling and insulin resistance involve activation of the protein kinases JNK and DGKs. These findings are expected to contribute critical insights for the development of safe and effective therapeutic strategies for weight control.

Additional Information

Language: English
Date: 2011
Adipocytes, cJun N-terminal kinase, Diacylglycerol, Inflammation, Insulin Resistance
Linoleic acid $x Therapeutic use
Obesity $x Treatment

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