The antiobesity mechanism of conjugated linoleic acid

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

Abstract: Given the steady rise in obesity worldwide, it is important to identify dietary compounds that prevent adiposity. One dietary strategy is supplementation with conjugated linoleic acid (CLA), which has been demonstrated to reduce body fat mass. However, side effects associated with CLA supplementation include inflammation, insulin resistance, and dyslipidemia. Elucidation of the antiobesity mechanism of CLA is critical for evaluating its efficacy and safety as a dietary supplement for treating obesity. Therefore, this research examined the upstream mechanism by which CLA induced inflammation, insulin resistance, and delipidation of human adipocytes. Our research group has previously demonstrated that trans-10, cis-12 (10,12) CLA causes delipidation of human adipocytes via activating nuclear factor kappa B (NF?B) and mitogen-activated protein kinase / extracellular signal-regulated kinase kinase (MEK/ERK) signaling, leading to inflammation and the suppression of peroxisome proliferator activated receptor (PPAR?) and decreased glucose and fatty acid uptake. Based on these findings, the following questions were addressed using primary cultures of newly differentiated human adipocytes as a cell model 1) How does CLA impact PPAR? activity?, 2) What upstream mechanisms activate ERK, NF?B and induce inflammation?, and 3) Does resveratrol, a phenolic phytochemical with antioxidant properties, attenuate CLA-induced inflammation, insulin resistance, and delipidation? Answers to these questions were as follows. 1) 10,12 CLA antagonized ligand-dependent PPAR? activity, possibly via PPAR? phosphorylation by ERK. 10,12 CLA suppression of PPAR? and insulin-stimulated glucose uptake, along with delipidation were partially rescued by co-supplementation with the PPAR? agonist BRL, further supporting CLA antagonizing PPAR?. 2) Cultures treated with TMB-8, an inhibitor of calcium release from the endoplasmic reticulum or KN-62, an inhibitor of calcium/calmodulin-dependent kinase II (CAMKII) attenuated 10,12 CLA-mediated reactive oxygen species (ROS) production, mitogen-activated protein kinase (MAPK) activation, inflammatory gene induction, and insulin resistance. These data suggested that 10,12 CLA-mediated inflammation and insulin resistance are dependent on calcium release from the endoplasmic reticulum or CAMKII. 3) Treatment with resveratrol prevented 10,12 CLA-mediated inflammation and insulin resistance by attenuating intracellular calcium, ROS, and inflammation, by increasing PPAR? activity. Collectively, these data suggest that one of the antiobesity mechanisms of 10,12 CLA is inducing cellular stress and inflammation which antagonize PPAR?, leading to insulin resistance and delipidation of human adipocytes.

Additional Information

Language: English
Date: 2009
Obesity, Adiposity, Conjugated Linoleic Acid (CLA)
Obesity $x Chemotherapy $x Research.
Linoleic acid.
Fat cells $x Growth $x Molecular aspects.
Adipose tissues.

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