A Research Blog

In a recent Biochemical and Biophysical Research Communications study, Assistant Professor Rohit Sinha and Professor Paul Yen from the Cardiovascular and Metabolic Disorders Programme at Duke-NUS Medical School describe the role of short chain fatty acids (SCFAs) in the liver.

We start our journey in the gut, where trillions of microbes and bacteria make themselves at home. These microbes and bacteria are responsible for producing SCFAs, namely acetate, butyrate and propionate, via anaerobic fermentation. By converting dietary fiber to SCFAs, the gut microbiome not only provides fuel to the intestinal epithelial cells, but the SCFAs produced also make their way to the liver via the entero-hepatic circulation to affect metabolism through lipogenesis and gluconeogenesis.

As SCFAs reach the liver, it is a hive of activity, synthesizing lipids and carbohydrates, storing carbohydrates and even breaking down toxins. With such high biosynthetic activity and protein turnover rate in the liver, the process of autophagy is essential to remove cellular debris and pathogens to maintain healthy liver function. Autophagy is the self-eating cellular mechanism that responds to stressors such as protein toxicity, metabolic dysregulation, infection and carcinogenesis. If autophagy is disrupted in the liver, it could contribute to the development of liver diseases, including alcoholic and non-alcoholic fatty liver diseases.

So, SCFAs spring into action in liver cells to regulate autophagy via the PPARγ-UCP2-AMPK pathway. Turning on this pathway induces the formation of autophagosomes, the compartment responsible for ingesting debris and pathogens within the cell, and increases the autophagic degradation activity in liver cells. In mice, reduction of SCFA production by ablating the gut microbiome through chronic antibiotic administration similarly appears to reduce autophagy.

From the gut to the liver, the adventure of SCFAs continues!


(Image credit: Iannucci LF et al./Biochemical and Biophysical Research Communications)


Moral of the story: Maintenance of gut microbiome and intake of dietary fiber is important to ensure production of SCFAs to sustain autophagy in the liver for normal function


Read the full paper at: http://www.sciencedirect.com/science/article/pii/S0006291X16317508


Funding Information

This work was supported by the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist Award (NMRC/CSA/0054/2013), and by the National Research Foundation Singapore under its Cooperative Basic Research Grants – New Investigators Grant (NMRC/BNIG/2025/2014) and administered by the Singapore Ministry of Health’s National Medical Research Council.


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