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Intestinal mcirobiota and the development of diet induced obesity: the role of fiber and short chain fatty acids

Subject Area Nutritional Sciences
Term from 2013 to 2018
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 234578296
 
Numerous environmental and genetic factors are thought to contribute to the world wide increase in obesity development. Recently, the gut microbiota has been suggested as a new factor to be actively involved in energy metabolism and development of obesity and associated disorders. Composition of the gastrointestinal microbiota is largely influenced by the diet and high fat diets are thought to induce gut microbiota with an increased capacity of energy harvest, although the mechanisms how gut microbiota affects obesity development are still elusive. Here we will focus on the role of short chain fatty acids (SCFA: mainly acetate, propionate and butyrate) which are produced from dietary fibers by bacterial fermentation. We aim to clarify the apparent paradox that fiber and SCFA are on one hand considered to prevent the development of obesity and associated disorders but on the other might provide additional energy to the host which could promote the development of obesity. In order to resolve this paradox we want to test the following hypotheses: (i) Fiber effects on diet induced obesity vary over time (beneficial short term effects vs. obesity promoting long term effects). (ii) The SCFA composition produced by fermentation affects host energy metabolism (acetate as rather obesity promoting SCFA vs. propionate as obesity preventing SCFA). (iii) Interactions between dietary fat and fiber type lead to the establishment of gut microbiota with different obesogenic potential (obesity promoting vs. obesity preventing). To this end we will perform feeding studies with mice using high fat diets supplemented with different types of fiber and SCFA mixtures with different acetate:propionate ratios, fed for different time periods. We will investigate microbial fermentation (SCFA concentrations in caecum, portal and peripheral blood), microbiota composition, and host energy metabolism (diet digestibility, energy intake and expenditure, substrate oxidation, liver and adipose tissue lipid and glucose metabolism). For clarification of mechanisms we will further analyze gut permeability, inflammation markers and metabolic endotoxemia, as well as expression of gut derived satiety hormones (PYY and GLP1), and expression of SCFA receptors FFA3 and FFA3 in intestinal mucosa, liver and adipose tissue.
DFG Programme Research Grants
 
 

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