Cardiotrofina-1implicación en obesidad y complicaciones metabólicas asociadas

Resumen

Obesity and health problems associated with overweight have epidemic characteristics in developed countries. The increased in fat stores in white adipose tissue (WAT) causes insulin resistance and diabetes. To treat obesity drugs are needed to stimulate the output of fat of WAT and accelerate its combustion in muscle. Cardiotrophin-1 (CT-1), a protein produced by the WAT, muscle and liver, has these characteristics, so it could be a novel treatment for obesity and diabetes. Our research group observed that animals lacking CT-1 showed a significant decrease in energy expenditure and, over time, became obese and diabetic. Researchers also found that injection of recombinant CT-1 (rCT-1) to obese mice increased the burning of fat and decreased body weight as a result of decreased fat depots. rCT-1 treatment decreased appetite, however, the weight loss was not only due to decreased food intake but also an effect of CT-1 on energy consumption, which is greatly stimulated by this protein. Moreover, our research group observed elevated circulating levels of CT-1 in obese individuals and reduced after weight loss. The postprandial elevation of glucose and insulin levels after a high carbohydrate test meal is not able to induce the production of CT-1. In contrast, a positive correlation between postprandial changes in free fatty acids (FFA) and CT-1 levels after the ingestion of a high fat test meal was observed. These results, together with increased CT-1 levels observed after administration of a lipid emulsion in rodents and in cultured adipocytes treated with AGL, reveal a key role of FFA in regulating CT-1 levels. In conclusion, CT-1 is a nutritionally regulated cytokine which plays an important role in modulating glucose and lipid metabolism and energy homeostasis, with therapeutic potential in obesity and related metabolic diseases.