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PhD research provides new leads against obesity and type 2 diabetes

26 September 2016 - Infusion of short-chain fatty acids (SCFA) into the colon increases fat oxidation and energy expenditure in overweight people. This is the key message from research by Dr Emanuel Canfora, who defended his thesis Friday 23 September at Maastricht University. His work provides leads for the prevention and treatment of obesity and type 2 diabetes.

The gastrointestinal microbiota and its products are thought to be involved in the development of metabolic disorders such as obesity and type 2 diabetes. The microbiota ferment indigestible foods, leading to the production of a variety of metabolites, including the SCFAs acetate, propionate and butyrate. “According to animal studies, SCFA are involved in the regulation of body weight and insulin sensitivity and may, at least in part, explain the beneficial metabolic effects of dietary-fibre intake”, says Canfora.

Microbiota, energy balance and metabolism
Canfora investigated whether these effects also applied to humans. He studied correlations and underlying mechanisms, combining short and long-term, in vivo, human intervention studies, with a range of in vitro experiments with stem cells derived from human adipose tissue (hMADS). 

Increased fat oxidation
The research demonstrated that SCFA infusions in the distal, but not proximal, colon increased fat oxidation, energy expenditure, blood levels of the appetite-suppressing hormone PYY and attenuated whole-body lipolysis. “However, in a longer-term, 12-week intervention study with fibre supplements, we were unable to demonstrate an increase in faecal and fasting plasma SCFA, following a fibre-rich diet, in obese, pre-diabetic participants”, stresses Canfora. In addition, the researchers could not detect beneficial effects on insulin sensitivity and on parameters of energy metabolism. “A reason for the lack of effects could be related to the site of fibre fermentation, which is likely to occur, primarily, in the proximal part of the colon.”

Canfora, therefore, asks for different strategies, focussing on enhancing SCFA in the distal colon and systemic circulation, via intake of food product and ingredients. “These insights would accelerate the development of advanced supplements and therapies against obesity and diabetes.” The scientist will continue this research as a post-doc at Maastricht University.

New pathways
The PhD work also revealed new insights into the processes taking place in human adipose tissue. “We were able to further characterize pathways for the breakdown of fatty acids in these cells. For instance, we demonstrated that the SCFA acetate, decreases intracellular lipolysis via attenuated hormone-sensitive lipase phosphorylation. SCFA therefore might affect adipose tissue lipid-buffering capacity and lipid spillover. This could ultimately result in attenuated ectopic fat accumulation and improved insulin action in insulin sensitive tissues. Consequently, enhancing the systemic acetate availability might be a strategy to improve obesity-related insulin resistance.”

Canfora highly values the close collaboration between scientists of varying disciplines at TiFN. “In the first study, for example, our aim was to study/identify the effects of SCFA at different sites in the colon”, he says. “Together with specialists from our academic hospital, of which a number were also involved with TiFN, we found a practical approach using endoscopy tools.”

As a PhD fellow, he also appreciated his proximity to the food industry. “It was fascinating to see, up close, how industry works, and the expert meetings inspired my research.”