Acetate as metabolic target in the prevention of overweight-related chronic metabolic disorders
Description: The connection between gut microbiota and obesity-related cardiometabolic disorders is increasingly recognized. Our gut microbiota affect the cardiometabolic phenotype by fermenting indigestible dietary components thereby producing short-chain fatty acids (SCFA). This may then affect adipose tissue function and ectopic fat storage thereby modulating insulin sensitivity. Our recent findings, using an unique design to administer acetate in the colon, show that distal, and not proximal, colonic acetate administration in healthy volunteers, in the amount achieved by a high fibre diet, has pronounced effects on lipolysis, fat oxidation and inflammatory profile. Based on this, we hypothesize that acetate when reaching a gut and systemic concentration within the high physiological range, is an important link between our gut microbiota and metabolic health by improving adipose tissue function, preventing lipid overflow and skeletal muscle fat accumulation thereby improving insulin sensitivity.
The objective of this proposal are to 1) screen which dietary fibre(s) will yield a high physiological colonic acetate concentration in ?in vitro? fermentation models, 2) investigate how key microbes are involved in a high acetate production and 3) to examine whether a dietary fibre, which yields the optimal gut and circulating acetate concentration, is able to reverse high-fat diet-induced insulin resistance (proof-of-concept study). Our approach is to use state-of-the art methodology for detailed human physiological and cellular/molecular phenotyping, microbiota composition and activity profiling in combination with ?in vitro? digestion models. The proposed studies will provide information for new strategies in nutritional prevention of insulin resistance and chronic metabolic diseases in adults and elderly.
Funding type: grant
Funder scheme: Partnership NWO-CCC 2015 ALW
Start date: 2016-06-15
End date: 2021-11-30
Investigator: Ellen Blaak
Institution: Maastricht University
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: ALWCC.2015.5
OpenAlex ID: G6653572105