ISCHOM II: Cocoa Improves Hepatic Lipid Metabolism & ZDF. CORDERO-HERRERA,I.

3.4. Cocoa-Rich Diet Improves Hepatic Lipid Metabolism in Zucker Diabetic Fatty Rats 

Cordero-Herrera, I.; Martín, M.A.; Fernández-Millán, E.; Álvarez, C.; Goya, L.; Ramos S. * 

Background and objectives

Diabetes is associated with altered lipid metabolism that could lead to ectopic-hepatic lipid deposition. Cocoa has been suggested to exert different biological activities contributing to prevent alterations of lipid metabolism as occurs in type 2 diabetes. The aim of the present study is to analyze the role of a cocoa-enriched diet in improving lipid metabolism in the liver of type 2 diabetic Zucker diabetic fatty (ZDF) rats.

Methodology

Male ZDF rats were fed a control or cocoa-rich diet (10%), and Zucker lean (ZL) animals received the control diet. Serum and hepatic lipid levels, protein kinase B (AKT), 5 1 -AMP-activated protein kinase (AMPK), protein kinase Cζ (PKCζ), fatty acid synthase (FAS), sterol regulatory element-binding protein 1 (SREBP-1) and proliferator-activated receptor α (PPARα) expression were evaluated. 

Results

ZDF rats fed with cocoa decreased body weight gain and improved circulating and hepatic lipid levels, namely triglycerides, cholesterol and non-esterified fatty acids. The lipid-lowering effect was related to the diminished synthesis mediated by SREBP1-c and FAS and the increased fatty acid oxidation (values of PPARα). All these effects depend on AMPK, AKT and PKCζ, whose levels of phosphorylation were returned to control values upon cocoa administration in ZDF rats. 

Conclusion

Cocoa improves lipid metabolism in ZDF rats through the modulation of multiple signalling pathways. 

Acknowledgments

Grants AGL2010-17579, BFU2011-25420 and CIBERDEM from MICINN. I. Cordero-Herrera is a fellow of the FPI predoctoral program (MICINN).

Referencias: ISCHOM II: Barcelona 2015. Nutrients

ISCHOM II: Cocoa & diabetes. GOYA,L.

2.6. Could a Cocoa Diet Be Beneficial for Diabetes? 

Goya, L. 

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by sustained hyperglycemia that results from defects in insulin secretion, insulin action or a combination of both. Prevalence of T2DM is increasing globally and it has reached epidemic proportions; in fact, diabetes is currently one of the most costly and burdensome chronic diseases (Whiting, D.R., et al. Diabetes Res. Clin. Pract. 2011, 94, 311–321). 

Despite the fact that several drugs are available for the treatment of diabetes, adverse effects and drug resistance are of great concern. Therefore, there is an urgent need to continue working on the prevention and control of this pathology and, as a promising alternative, researchers are seeking natural products to prevent or treat T2DM because of their potential beneficial effects on health and because of their safeness (Williamson, G. Mol. Nutr. Food Res. 2013, 57, 48–57). 

Cocoa has been shown to exert antidiabetic effects by lowering glucose levels. We have recently shown that cocoa flavanols may have antidiabetic potential in vitro by promoting the survival and function of pancreatic beta-cells and improving the insulin signaling pathway in liver cells (Cordero-Herrera, I., et al. Mol. Nutr. Food Res. 2013, 57, 974–985; Martín, M.A., et al. Mol. Nutr. Food Res. 2014, 58, 447–456). 

Therefore, we decided to investigate the effects of a cocoa-rich diet in Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed a control or cocoa-rich diet (10%), and Zucker lean animals received the control diet. The ZDF rats supplemented with cocoa showed a significant decrease in body weight gain, glucose and insulin levels, as well as an improved glucose tolerance. Our results showed that cocoa feeding during the pre-diabetic state reduces insulin resistance and increases beta-cell mass and function in ZDF rats (Fernández-Millán, E., et al. Mol. Nutr. Food Res. 2015, 59, 820–824). 

Cocoa-rich diet further ameliorated the hepatic insulin resistance by favoring insulin signaling, glucose transport, glycolysis and glycogenesis and reducing gluconeogenesis (Cordero-Herrera, I., et al. J. Nutr. Biochem. 2015, 26, 704–712). 

Furthermore, a cocoa-rich diet protects the hepatocytes of ZDF rats by improving their antioxidant competence and by ameliorating diabetes-induced damage to lipid metabolism through multiple signaling pathways (Cordero-Herrera, I., et al. Food Res. Int. 2015, 69, 194–201). 

These findings provide the first in vivo evidence that a cocoa-rich diet may delay the loss of functional beta-cell mass and protect liver activity in order to delay the onset of T2DM.

ISCHOM II: Barcelona 2016. Nutrients.