Cellular
and Molecular Mechanisms of CLA Action
Martha A. Belury, Carol S. Kennedy Professor of Human Nutrition,
Ohio
State University, Columbus, OH.
The
incidence of type 2 diabetes mellitus is increasing in epidemic proportions
in developed countries worldwide. Type 2 diabetes arises from a variety
of etiological factors including environmental factors that affect obesity
and dyslipidemia and non-modifiable factors including genetics, ethnicity
and age. The delay of onset or therapy to reduce the severity of the disease
through diet and other lifestyle approaches offers the possibility of
reducing the severity of co-morbid disorders that contribute to morbidity
and mortality. Co-morbid disorders that often exist with type 2 diabetes
include cardiovascular disease, retinopathy and neuropathy. Numerous studies
have shown that the dietary fatty acids, conjugated linoleic acids (CLA),
reduce adiposity in experimental animals and recent studies suggest similar
findings in humans. We have identified that dietary CLA delays the onset
and improve lipid profiles in a rat model for type 2 diabetes. Subsequent
studies have demonstrated that CLA may improve glucose metabolism by enhancing
glucose uptake into muscle. Numerous investigators have shown CLA alters
deposition of body fat in a depot-specific pattern. In non-diabetic animals
that has also resulted in increased insulin resistance. We and others
have found that CLA modulates numerous pathways involving lipid signaling
and fatty acid oxidation. Pathways that may explain CLA's anti-adipogenic
effects include D6-, D9 desaturase metabolism as well as pathways modified
by the transcription factor, peroxisome proliferators-activated receptors
(PPARs). The potential ability of different isomers of CLA at various
doses and durations (short vs. long term) to alter metabolic pathways
through altering gene expression to ultimately affect type 2 diabetes
mellitus will be discussed.
