Authors: Cani, Patrice D.; Delzenne, Nathalie M.

Source: Current Pharmaceutical Design, Volume 15, Number 13, May 2009 , pp. 1546-1558(13)

Publisher: Bentham Science Publishers

Abstract:

Obesity is now classically characterized by a cluster of several metabolic disorders, and by a low grade inflammation. The evidence that the gut microbiota composition can be different between healthy and or obese and type 2 diabetic patients has led to the study of this environmental factor as a key link between the pathophysiology of metabolic diseases and the gut microbiota. Several mechanisms are proposed linking events occurring in the colon and the regulation of energy metabolism, such as i.e. the energy harvest from the diet, the synthesis of gut peptides involved in energy homeostasis (GLP-1, PYY…), and the regulation of fat storage. Moreover, the development of obesity and metabolic disorders following a high-fat diet may be associated to the innate immune system. Indeed, high-fat diet feeding triggers the development of obesity, inflammation, insulin resistance, type 2 diabetes and atherosclerosis by mechanisms dependent of the LPS and/or the fatty acids activation of the CD14/TLR4 receptor complex. Importantly, fat feeding is also associated with the development of metabolic endotoxemia in human subjects and participates in the low-grade inflammation, a mechanism associated with the development of atherogenic markers. Finally, data obtained in experimental models and human subjects are in favour of the fact that changing the gut microbiota (with prebiotics and/or probiotics) may participate in the control of the development of metabolic diseases associated with obesity. Thus, it would be useful to find specific strategies for modifying gut microbiota to impact on the occurrence of metabolic diseases.

Keywords: high fat diet; metabolic endotoxemia- obesity; prebiotics; gut peptides; bifidobacteria; gut bacteria; cardiovascular diseases

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161209788168164

Affiliations: 1: Unit PMNT-7369, Av. E. Mounier, 73/69, B-1200 Brussels, Belgium.

Publication date: 2009-05-01

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  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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