Effects of elevating colonic propionate on liver fat content in overweight adults with non-alcoholic fatty liver disease: a pilot study

E.S. Chambers, A. Viardot, A. Psichas, D.J. Morrison, K.G. Murphy, S.E.K. Zac-Varghese, K. MacDougall, T. Preston, M.C. Tedford, J.D. Bell, E.L. Thomas, S. Mt-Isa, D. Ashby, W.S. Dhillo, S.R. Bloom, W.G. Morley, S. Clegg, G. Frost

Research output: Contribution to journalMeeting Abstract

Abstract

It is estimated that 20-30% of adults in developed countries have non-alcoholic fatty liver disease (NAFLD), a condition characterized by the accumulation of fat within the liver(1). NAFLD is commonly associated with an increased risk of developing Type 2 diabetes. Positive physiological effects have been linked with the production of short chain fatty acids (SCFA) by colonic fermentation of non-digestible carbohydrate (NDC), including reductions in hepatic fat content(2). We have developed a novel inulin-propionate ester, whereby the SCFA propionate is bound to the NDC inulin. The bound propionate is only released from the inulin carrier molecule through bacterial fermentation in the colon allowing the targeted delivery of gram quantities of propionate. In humans, ~90% of propionate produced in the colon is extracted from portal blood by the liver. Propionate is a known gluconeogenic substrate, and the energy to drive this anabolic pathway may derive from increased hepatic fat oxidation(3). We hypothesised that long-term elevations in colonic propionate production would reduce liver fat in adults with NAFLD. Sixteen participants aged 40-65 years, with a BMI of 25-40 kg/m2 were recruited and intrahepatocellular lipid (IHCL) was determined using 1H magnetic resonance spectroscopy (MRS)(4). Participants were identified as having NAFLD on the basis of a liver fat content >5*5%(5). Participants were provided with either 10 g/day propionate ester (n = 11) or 10 g/day inulin control (n = 5) to add to their normal diet for a 24 week intervention period. After 24 weeks of dietary supplementation, measurements taken at baseline were repeated. In the propionate ester group a significant reduction in IHCL content post-intervention was observed (22*1% to 15*9%; P = 0*038). This effect was not found in the control group (19*1% to 18*7%; P = 0*576). An improvement in liver function tests (alanine amino transferase and aspartate aminotransferase) was also observed within the propionate ester group, whilst these liver function tests were unchanged in the control group. There was no significant change in body weight following the intervention period in either group. Our data provides the first direct evidence in humans that gut-derived propionate can reduce liver fat in adults with NAFLD. Targeting increased colonic propionate levels, delivered via enriched food products, may offer a public health solution to the increased prevalence of NAFLD at the population level and warrants further investigation.
Original languageEnglish
Article numberE30
JournalProceedings of Nutrition Society
Volume74
Issue numberOCE1
DOIs
Publication statusPublished - 2014

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Propionates
Fats
Liver
Inulin
Esters
Volatile Fatty Acids
Liver Function Tests
Fermentation
Non-alcoholic Fatty Liver Disease
Colon
Carbohydrates
Fortified Food
Lipids
Control Groups
Body Weight Changes
Transferases
Aspartate Aminotransferases
Dietary Supplements
Developed Countries
Alanine

Cite this

Chambers, E. S., Viardot, A., Psichas, A., Morrison, D. J., Murphy, K. G., Zac-Varghese, S. E. K., ... Frost, G. (2014). Effects of elevating colonic propionate on liver fat content in overweight adults with non-alcoholic fatty liver disease: a pilot study. Proceedings of Nutrition Society, 74(OCE1), [E30]. https://doi.org/10.1017/S0029665115000452
Chambers, E.S. ; Viardot, A. ; Psichas, A. ; Morrison, D.J. ; Murphy, K.G. ; Zac-Varghese, S.E.K. ; MacDougall, K. ; Preston, T. ; Tedford, M.C. ; Bell, J.D. ; Thomas, E.L. ; Mt-Isa, S. ; Ashby, D. ; Dhillo, W.S. ; Bloom, S.R. ; Morley, W.G. ; Clegg, S. ; Frost, G. / Effects of elevating colonic propionate on liver fat content in overweight adults with non-alcoholic fatty liver disease : a pilot study. In: Proceedings of Nutrition Society. 2014 ; Vol. 74, No. OCE1.
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title = "Effects of elevating colonic propionate on liver fat content in overweight adults with non-alcoholic fatty liver disease: a pilot study",
abstract = "It is estimated that 20-30{\%} of adults in developed countries have non-alcoholic fatty liver disease (NAFLD), a condition characterized by the accumulation of fat within the liver(1). NAFLD is commonly associated with an increased risk of developing Type 2 diabetes. Positive physiological effects have been linked with the production of short chain fatty acids (SCFA) by colonic fermentation of non-digestible carbohydrate (NDC), including reductions in hepatic fat content(2). We have developed a novel inulin-propionate ester, whereby the SCFA propionate is bound to the NDC inulin. The bound propionate is only released from the inulin carrier molecule through bacterial fermentation in the colon allowing the targeted delivery of gram quantities of propionate. In humans, ~90{\%} of propionate produced in the colon is extracted from portal blood by the liver. Propionate is a known gluconeogenic substrate, and the energy to drive this anabolic pathway may derive from increased hepatic fat oxidation(3). We hypothesised that long-term elevations in colonic propionate production would reduce liver fat in adults with NAFLD. Sixteen participants aged 40-65 years, with a BMI of 25-40 kg/m2 were recruited and intrahepatocellular lipid (IHCL) was determined using 1H magnetic resonance spectroscopy (MRS)(4). Participants were identified as having NAFLD on the basis of a liver fat content >5*5{\%}(5). Participants were provided with either 10 g/day propionate ester (n = 11) or 10 g/day inulin control (n = 5) to add to their normal diet for a 24 week intervention period. After 24 weeks of dietary supplementation, measurements taken at baseline were repeated. In the propionate ester group a significant reduction in IHCL content post-intervention was observed (22*1{\%} to 15*9{\%}; P = 0*038). This effect was not found in the control group (19*1{\%} to 18*7{\%}; P = 0*576). An improvement in liver function tests (alanine amino transferase and aspartate aminotransferase) was also observed within the propionate ester group, whilst these liver function tests were unchanged in the control group. There was no significant change in body weight following the intervention period in either group. Our data provides the first direct evidence in humans that gut-derived propionate can reduce liver fat in adults with NAFLD. Targeting increased colonic propionate levels, delivered via enriched food products, may offer a public health solution to the increased prevalence of NAFLD at the population level and warrants further investigation.",
author = "E.S. Chambers and A. Viardot and A. Psichas and D.J. Morrison and K.G. Murphy and S.E.K. Zac-Varghese and K. MacDougall and T. Preston and M.C. Tedford and J.D. Bell and E.L. Thomas and S. Mt-Isa and D. Ashby and W.S. Dhillo and S.R. Bloom and W.G. Morley and S. Clegg and G. Frost",
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language = "English",
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Chambers, ES, Viardot, A, Psichas, A, Morrison, DJ, Murphy, KG, Zac-Varghese, SEK, MacDougall, K, Preston, T, Tedford, MC, Bell, JD, Thomas, EL, Mt-Isa, S, Ashby, D, Dhillo, WS, Bloom, SR, Morley, WG, Clegg, S & Frost, G 2014, 'Effects of elevating colonic propionate on liver fat content in overweight adults with non-alcoholic fatty liver disease: a pilot study' Proceedings of Nutrition Society, vol. 74, no. OCE1, E30. https://doi.org/10.1017/S0029665115000452

Effects of elevating colonic propionate on liver fat content in overweight adults with non-alcoholic fatty liver disease : a pilot study. / Chambers, E.S.; Viardot, A.; Psichas, A.; Morrison, D.J.; Murphy, K.G.; Zac-Varghese, S.E.K.; MacDougall, K.; Preston, T.; Tedford, M.C.; Bell, J.D.; Thomas, E.L.; Mt-Isa, S.; Ashby, D.; Dhillo, W.S.; Bloom, S.R.; Morley, W.G.; Clegg, S.; Frost, G.

In: Proceedings of Nutrition Society, Vol. 74, No. OCE1, E30, 2014.

Research output: Contribution to journalMeeting Abstract

TY - JOUR

T1 - Effects of elevating colonic propionate on liver fat content in overweight adults with non-alcoholic fatty liver disease

T2 - a pilot study

AU - Chambers, E.S.

AU - Viardot, A.

AU - Psichas, A.

AU - Morrison, D.J.

AU - Murphy, K.G.

AU - Zac-Varghese, S.E.K.

AU - MacDougall, K.

AU - Preston, T.

AU - Tedford, M.C.

AU - Bell, J.D.

AU - Thomas, E.L.

AU - Mt-Isa, S.

AU - Ashby, D.

AU - Dhillo, W.S.

AU - Bloom, S.R.

AU - Morley, W.G.

AU - Clegg, S.

AU - Frost, G.

PY - 2014

Y1 - 2014

N2 - It is estimated that 20-30% of adults in developed countries have non-alcoholic fatty liver disease (NAFLD), a condition characterized by the accumulation of fat within the liver(1). NAFLD is commonly associated with an increased risk of developing Type 2 diabetes. Positive physiological effects have been linked with the production of short chain fatty acids (SCFA) by colonic fermentation of non-digestible carbohydrate (NDC), including reductions in hepatic fat content(2). We have developed a novel inulin-propionate ester, whereby the SCFA propionate is bound to the NDC inulin. The bound propionate is only released from the inulin carrier molecule through bacterial fermentation in the colon allowing the targeted delivery of gram quantities of propionate. In humans, ~90% of propionate produced in the colon is extracted from portal blood by the liver. Propionate is a known gluconeogenic substrate, and the energy to drive this anabolic pathway may derive from increased hepatic fat oxidation(3). We hypothesised that long-term elevations in colonic propionate production would reduce liver fat in adults with NAFLD. Sixteen participants aged 40-65 years, with a BMI of 25-40 kg/m2 were recruited and intrahepatocellular lipid (IHCL) was determined using 1H magnetic resonance spectroscopy (MRS)(4). Participants were identified as having NAFLD on the basis of a liver fat content >5*5%(5). Participants were provided with either 10 g/day propionate ester (n = 11) or 10 g/day inulin control (n = 5) to add to their normal diet for a 24 week intervention period. After 24 weeks of dietary supplementation, measurements taken at baseline were repeated. In the propionate ester group a significant reduction in IHCL content post-intervention was observed (22*1% to 15*9%; P = 0*038). This effect was not found in the control group (19*1% to 18*7%; P = 0*576). An improvement in liver function tests (alanine amino transferase and aspartate aminotransferase) was also observed within the propionate ester group, whilst these liver function tests were unchanged in the control group. There was no significant change in body weight following the intervention period in either group. Our data provides the first direct evidence in humans that gut-derived propionate can reduce liver fat in adults with NAFLD. Targeting increased colonic propionate levels, delivered via enriched food products, may offer a public health solution to the increased prevalence of NAFLD at the population level and warrants further investigation.

AB - It is estimated that 20-30% of adults in developed countries have non-alcoholic fatty liver disease (NAFLD), a condition characterized by the accumulation of fat within the liver(1). NAFLD is commonly associated with an increased risk of developing Type 2 diabetes. Positive physiological effects have been linked with the production of short chain fatty acids (SCFA) by colonic fermentation of non-digestible carbohydrate (NDC), including reductions in hepatic fat content(2). We have developed a novel inulin-propionate ester, whereby the SCFA propionate is bound to the NDC inulin. The bound propionate is only released from the inulin carrier molecule through bacterial fermentation in the colon allowing the targeted delivery of gram quantities of propionate. In humans, ~90% of propionate produced in the colon is extracted from portal blood by the liver. Propionate is a known gluconeogenic substrate, and the energy to drive this anabolic pathway may derive from increased hepatic fat oxidation(3). We hypothesised that long-term elevations in colonic propionate production would reduce liver fat in adults with NAFLD. Sixteen participants aged 40-65 years, with a BMI of 25-40 kg/m2 were recruited and intrahepatocellular lipid (IHCL) was determined using 1H magnetic resonance spectroscopy (MRS)(4). Participants were identified as having NAFLD on the basis of a liver fat content >5*5%(5). Participants were provided with either 10 g/day propionate ester (n = 11) or 10 g/day inulin control (n = 5) to add to their normal diet for a 24 week intervention period. After 24 weeks of dietary supplementation, measurements taken at baseline were repeated. In the propionate ester group a significant reduction in IHCL content post-intervention was observed (22*1% to 15*9%; P = 0*038). This effect was not found in the control group (19*1% to 18*7%; P = 0*576). An improvement in liver function tests (alanine amino transferase and aspartate aminotransferase) was also observed within the propionate ester group, whilst these liver function tests were unchanged in the control group. There was no significant change in body weight following the intervention period in either group. Our data provides the first direct evidence in humans that gut-derived propionate can reduce liver fat in adults with NAFLD. Targeting increased colonic propionate levels, delivered via enriched food products, may offer a public health solution to the increased prevalence of NAFLD at the population level and warrants further investigation.

U2 - 10.1017/S0029665115000452

DO - 10.1017/S0029665115000452

M3 - Meeting Abstract

VL - 74

JO - Proceedings of Nutrition Society

JF - Proceedings of Nutrition Society

SN - 0029-6651

IS - OCE1

M1 - E30

ER -