Supplementation with a mixture of CLA isomers or 10,12 CLA alone reduces adiposity consistently in animal models, especially in rodents, but has been shown to reduce adiposity in only some human studies. Potential reasons for these species differences include 1) the CLA isomers used, 2) the dosage administered, and 3) age, body weight, body fat, or metabolic status of the animals or subjects. Of the major isomers, only 10,12 CLA reduces adiposity or TG content of WAT. Dosage differences among species can be considerable; rodent studies generally use ~20 times more CLA/kg body weight compared to human studies.
Potential mechanisms responsible for these antiobesity properties of 10,12 CLA include 1) decreasing energy intake by suppressing appetite 2) increasing energy expenditure in WAT, muscle, and liver tissue, or LBM, 3) decreasing lipogenesis or adipogenesis, 4) increasing lipolysis or delipidation, and 5) apoptosis via adipocyte stress, inflammation, and/or insulin resistance.
Based on these data, we propose the following working model () depicting the mechanisms by which 10,12 CLA decreases WAT mass. We speculate that 10,12 CLA binds to a cell surface FA receptor, or diffuses or flip-flops into adipocytes, thereby activating upstream signals. These upstream signals induce an ISR, FFA release, and activation of NFκB and MAPKs that may directly antagonize PPARγ activity. Increased release of PGs and cytokines may further antagonize PPARγ activity, leading to insulin resistance and delipidation. The resulting FFA accumulation in blood, liver, and muscle increases FFA oxidation and FFA-induced insulin resistance in these tissues. If energy expenditure is not sufficient to completely oxidize these elevated levels of FFAs, hyperlipidemia, hyperglycemia, and lipodystrophy can result.
Figure 7 Working model by which 10,12 CLA causes insulin resistance and delipidation in adipocytes. We propose that 10,12 CLA induces upstream signals that cause 1) an ISR that increases apoptosis, FFA release, and inflammatory gene expression, 2) NFκB (more ...)
Future studies are needed to identify potential upstream mediators of this proposed stress cascade in adipocytes. Elucidating these mechanisms will provide valuable information on the efficacy, specificity, and potential side effects of CLA isomers as dietary strategies for weight loss or maintenance. Such knowledge is essential for the effective and safe use of CLA supplements to control obesity.