Animal Models

Reprogramming of hepatic fat accumulation and 'browning' of adipose tissue by the short-chain fatty acid acetate

Abstract

Background/Objectives:

Short-chain fatty acids, produced by microbiome fermentation of carbohydrates, have been linked to a reduction in appetite, body weight and adiposity. However, determining the contribution of central and peripheral mechanisms to these effects has not been possible.

Subjects/Methods:

C57BL/6 mice fed with either normal or high-fat diet were treated with nanoparticle-delivered acetate, and the effects on metabolism were investigated.

Results:

In the liver, acetate decreased lipid accumulation and improved hepatic function, as well as increasing mitochondrial efficiency. In white adipose tissue, it inhibited lipolysis and induced 'browning', increasing thermogenic capacity that led to a reduction in body adiposity.

Conclusions:

This study provides novel insights into the peripheral mechanism of action of acetate, independent of central action, including ‘browning’ and enhancement of hepatic mitochondrial function.

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Acknowledgements

We thank Professor Alice Warley and Dr Gema Vizcay-Barrena from the Centre for Ultrastructural Imaging (King's College, London, UK) where TEM was carried out. A549 lung cancer cell lines (Parent and Rho0) were a kind gift from Dr Zhi Yao and Dr Gyorgy Szabadkai. This research was funded by Medical Research Council, UK.

Author contributions

JDB, GF, ELT and MS-A designed the experiments and wrote the manuscript. MS-A performed and analyzed most of the experiments. MS-A, LPB and ADM performed liposome formulation and delivery experiments. HP carried out NMR scans. NN conducted protein expression of A549 cells. All the authors provided critical feedback in preparation and writing the manuscript.

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Correspondence to J D Bell.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Sahuri-Arisoylu, M., Brody, L., Parkinson, J. et al. Reprogramming of hepatic fat accumulation and 'browning' of adipose tissue by the short-chain fatty acid acetate. Int J Obes 40, 955–963 (2016). https://doi.org/10.1038/ijo.2016.23

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