Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance

Kay H M Roumans; Lucas Lindeboom; Pandichelvam Veeraiah; Carlijn M E Remie; Esther Phielix; Bas Havekes; Yvonne M H Bruls; Martijn C G J Brouwers; Marcus Ståhlman; Marjan Alssema; Harry P F Peters; Renée de Mutsert; Bart Staels; Marja-Riitta Taskinen; Jan Borén; Patrick Schrauwen; Vera B Schrauwen-Hinderling

doi:10.1038/s41467-020-15684-0

Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance

Kay H M Roumans, Lucas Lindeboom, Pandichelvam Veeraiah, Carlijn M E Remie, Esther Phielix, Bas Havekes, Yvonne M H Bruls, Martijn C G J Brouwers, Marcus Ståhlman, Marjan Alssema, Harry P F Peters, Renée de Mutsert, Bart Staels, Marja-Riitta Taskinen, Jan Borén, Patrick Schrauwen, Vera B Schrauwen-Hinderling^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (1H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our 1H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity.

Original language	English
Article number	1891
Number of pages	11
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15684-0
Publication status	Published - 20 Apr 2020

Keywords

Adipose Tissue
Adult
Aged
Cross-Sectional Studies
Diabetes Mellitus, Type 2/metabolism
Fatty Acids/metabolism
Female
Humans
Insulin Resistance/physiology
Lipids
Lipogenesis/physiology
Liver/diagnostic imaging
Male
Middle Aged
Non-alcoholic Fatty Liver Disease/metabolism
Triglycerides/metabolism
RISK
LIVER-DISEASE
SPECTROSCOPY
STEATOSIS
CARDIOVASCULAR-DISEASE
MICE
BRAIN

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Cite this

Roumans, K. H. M., Lindeboom, L., Veeraiah, P., Remie, C. M. E., Phielix, E., Havekes, B., Bruls, Y. M. H., Brouwers, M. C. G. J., Ståhlman, M., Alssema, M., Peters, H. P. F., de Mutsert, R., Staels, B., Taskinen, M-R., Borén, J., Schrauwen, P., & Schrauwen-Hinderling, V. B. (2020). Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance. Nature Communications, 11(1), Article 1891. https://doi.org/10.1038/s41467-020-15684-0

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title = "Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance",

abstract = "Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (1H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our 1H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity.",

keywords = "Adipose Tissue, Adult, Aged, Cross-Sectional Studies, Diabetes Mellitus, Type 2/metabolism, Fatty Acids/metabolism, Female, Humans, Insulin Resistance/physiology, Lipids, Lipogenesis/physiology, Liver/diagnostic imaging, Male, Middle Aged, Non-alcoholic Fatty Liver Disease/metabolism, Triglycerides/metabolism, RISK, LIVER-DISEASE, SPECTROSCOPY, STEATOSIS, CARDIOVASCULAR-DISEASE, MICE, BRAIN",

author = "Roumans, {Kay H M} and Lucas Lindeboom and Pandichelvam Veeraiah and Remie, {Carlijn M E} and Esther Phielix and Bas Havekes and Bruls, {Yvonne M H} and Brouwers, {Martijn C G J} and Marcus St{\aa}hlman and Marjan Alssema and Peters, {Harry P F} and {de Mutsert}, Ren{\'e}e and Bart Staels and Marja-Riitta Taskinen and Jan Bor{\'e}n and Patrick Schrauwen and Schrauwen-Hinderling, {Vera B}",

note = "Funding Information: This research was in part financed by the Ministry of Economic Affairs and Climate Policy by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public–private partnerships and by Unilever R&D Wageningen. We acknowledge the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014-02 ENERGISE). L.L. is a recipient of a veni grant from ZonMW (016.veni.188.036) and a junior fellowship (2017.81.004) from the Diabetes Fonds (Dutch Diabetes Research Foundation). B.S. is a recipient of an Advanced ERC Grant (694717). V.B.S.-H. is a recipient of an ERC starting grant (grant no. 759161 {\textquoteleft}MRS in diabetes{\textquoteright}). Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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doi = "10.1038/s41467-020-15684-0",

language = "English",

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Roumans, KHM, Lindeboom, L, Veeraiah, P, Remie, CME, Phielix, E , Havekes, B , Bruls, YMH , Brouwers, MCGJ, Ståhlman, M, Alssema, M, Peters, HPF, de Mutsert, R, Staels, B, Taskinen, M-R, Borén, J, Schrauwen, P & Schrauwen-Hinderling, VB 2020, 'Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance', Nature Communications, vol. 11, no. 1, 1891. https://doi.org/10.1038/s41467-020-15684-0

TY - JOUR

T1 - Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance

AU - Roumans, Kay H M

AU - Lindeboom, Lucas

AU - Veeraiah, Pandichelvam

AU - Remie, Carlijn M E

AU - Phielix, Esther

AU - Havekes, Bas

AU - Bruls, Yvonne M H

AU - Brouwers, Martijn C G J

AU - Ståhlman, Marcus

AU - Alssema, Marjan

AU - Peters, Harry P F

AU - de Mutsert, Renée

AU - Staels, Bart

AU - Taskinen, Marja-Riitta

AU - Borén, Jan

AU - Schrauwen, Patrick

AU - Schrauwen-Hinderling, Vera B

N1 - Funding Information: This research was in part financed by the Ministry of Economic Affairs and Climate Policy by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public–private partnerships and by Unilever R&D Wageningen. We acknowledge the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014-02 ENERGISE). L.L. is a recipient of a veni grant from ZonMW (016.veni.188.036) and a junior fellowship (2017.81.004) from the Diabetes Fonds (Dutch Diabetes Research Foundation). B.S. is a recipient of an Advanced ERC Grant (694717). V.B.S.-H. is a recipient of an ERC starting grant (grant no. 759161 ‘MRS in diabetes’). Publisher Copyright: © 2020, The Author(s).

PY - 2020/4/20

Y1 - 2020/4/20

N2 - Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (1H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our 1H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity.

AB - Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (1H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our 1H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity.

KW - Adipose Tissue

KW - Adult

KW - Aged

KW - Cross-Sectional Studies

KW - Diabetes Mellitus, Type 2/metabolism

KW - Fatty Acids/metabolism

KW - Female

KW - Humans

KW - Insulin Resistance/physiology

KW - Lipids

KW - Lipogenesis/physiology

KW - Liver/diagnostic imaging

KW - Male

KW - Middle Aged

KW - Non-alcoholic Fatty Liver Disease/metabolism

KW - Triglycerides/metabolism

KW - RISK

KW - LIVER-DISEASE

KW - SPECTROSCOPY

KW - STEATOSIS

KW - CARDIOVASCULAR-DISEASE

KW - MICE

KW - BRAIN

U2 - 10.1038/s41467-020-15684-0

DO - 10.1038/s41467-020-15684-0

M3 - Article

C2 - 32312974

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1891

ER -