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Short-chain fatty acids in control of body weight and insulin sensitivity

Key Points

  • Short-chain fatty acids (SCFA), which are derived from gut microbial fermentation of indigestible foods, have important metabolic functions and are crucial for intestinal health

  • The discovery of SCFA receptors in many different tissues highlights that SCFA are involved in the crosstalk between the gut and peripheral tissues

  • In addition to their role in gut health and as signalling molecules, SCFA might enter the systemic circulation and directly affect substrate metabolism and function of peripheral tissues

  • SCFA might increase intestinal energy harvesting and promote the development of obesity, but could also increase energy expenditure and anorexic hormone production, as well as improving appetite regulation

  • Increasing evidence supports a beneficial role for SCFA in adipose tissue, skeletal muscle and liver substrate metabolism and function, thereby contributing to improved insulin sensitivity

  • Well-controlled human intervention studies investigating the role of SCFA and differential SCFA availability on gut and systemic metabolic health are eagerly awaited

Abstract

The connection between the gut microbiota and the aetiology of obesity and cardiometabolic disorders is increasingly being recognized by clinicians. Our gut microbiota might affect the cardiometabolic phenotype by fermenting indigestible dietary components and thereby producing short-chain fatty acids (SCFA). These SCFA are not only of importance in gut health and as signalling molecules, but might also enter the systemic circulation and directly affect metabolism or the function of peripheral tissues. In this Review, we discuss the effects of three SCFA (acetate, propionate and butyrate) on energy homeostasis and metabolism, as well as how these SCFA can beneficially modulate adipose tissue, skeletal muscle and liver tissue function. As a result, these SCFA contribute to improved glucose homeostasis and insulin sensitivity. Furthermore, we also summarize the increasing evidence for a potential role of SCFA as metabolic targets to prevent and counteract obesity and its associated disorders in glucose metabolism and insulin resistance. However, most data are derived from animal and in vitro studies, and consequently the importance of SCFA and differential SCFA availability in human energy and substrate metabolism remains to be fully established. Well-controlled human intervention studies investigating the role of SCFA on cardiometabolic health are, therefore, eagerly awaited.

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Figure 1: Interorgan crosstalk and obesity-induced insulin resistance.
Figure 2: SCFA and interorgan crosstalk.
Figure 3: The effect of SCFA on adipose tissue function.
Figure 4: SCFA and skeletal muscle substrate metabolism.
Figure 5: SCFA and liver function.

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Acknowledgements

Research in the authors' laboratory is funded by TI Food and Nutrition, a public–private partnership on precompetitive research in food and nutrition.

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Canfora, E., Jocken, J. & Blaak, E. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol 11, 577–591 (2015). https://doi.org/10.1038/nrendo.2015.128

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