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

• Published in: Nature communications Vol. 11; no. 1; pp. 1891 - 11
• Main Authors: Roumans, Kay H. M., Lindeboom, Lucas, Veeraiah, Pandichelvam, Remie, Carlijn M. E., Phielix, Esther, Havekes, Bas, Bruls, Yvonne M. H., Brouwers, Martijn C. G. J., Ståhlman, Marcus, Alssema, Marjan, Peters, Harry P. F., de Mutsert, Renée, Staels, Bart, Taskinen, Marja-Riitta, Borén, Jan, Schrauwen, Patrick, Schrauwen-Hinderling, Vera B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.04.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 59/57; 692/163/2743/137/773; 692/4020/4021/1607/2750; Acid resistance; Adipose Tissue; Adult; Aged; Cross-Sectional Studies; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Fatty acids; Fatty Acids - metabolism; Fatty liver; Female; Human health and pathology; Humanities and Social Sciences; Humans; Hépatology and Gastroenterology; Insulin; Insulin resistance; Insulin Resistance - physiology; Life Sciences; Lipid composition; Lipids; Lipogenesis; Lipogenesis - physiology; Liver - diagnostic imaging; Liver - metabolism; Magnetic resonance spectroscopy; Male; Middle Aged; Molecular Biology; Molekylärbiologi; multidisciplinary; Non-alcoholic Fatty Liver Disease - metabolism; Polyunsaturated fatty acids; Proton magnetic resonance; Science; Science (multidisciplinary); Sensitivity; Steatosis; Triglycerides - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15684-0

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 ( 1 H-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 1 H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity. Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Here, the authors use 1 H-MRS methodology to show hepatic SFA fraction is a measure of DNL and specifically may hamper hepatic insulin sensitivity.