title: Liver Fat Measured by MR Spectroscopy: Estimate of Imprecision and Relationship with Serum Glycerol, Caeruloplasmin and Non-Esterified Fatty Acids.
abstract: Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantitative estimation of liver fat. Knowledge of its imprecision, which comprises biological variability and measurement error, is required to design therapeutic trials with measurement of change. The role of adipocyte lipolysis in ectopic fat accumulation remains unclear. We examined the relationship between liver fat content and indices of lipolysis, and determine whether lipolysis reflects insulin resistance or metabolic liver disease. Imprecision of measurement of liver fat was estimated from duplicate measurements by MRS at one month intervals. Patients provided fasting blood samples and we examined the correlation of liver fat with indices of insulin resistance, lipolysis and metabolic liver disease using Kendall Tau statistics. The coefficient of variation of liver fat content was 14.8%. Liver fat was positively related to serum insulin (T = 0.48, p = 0.042), homeostasis model assessment (HOMA)-B% (T = -0.48, p = 0.042), and body mass index (BMI) (T = 0.59, p = 0.012); and inversely related to HOMA-S% (T = -0.48, p = 0.042), serum glycerol (T = -0.59, p = 0.014), and serum caeruloplasmin (T = 0.055, p = 0.047). Our estimate of total variability in liver fat content (14.8%) is nearly twice that of the reported procedural variability (8.5%). We found that liver fat content was significantly inversely related to serum glycerol but not to non-esterified fatty acids (NEFA), suggesting progressive suppression of lipolysis. Reduction of caeruloplasmin with increasing liver fat may be a consequence or a cause of hepatic steatosis.
authors.affiliation: Department of Clinical Biochemistry, Cobbett House, Central Manchester Foundation Trust, Oxford Road, Manchester M13 9WL, UK. michael.france@cmft.nhs.uk.
authors.forename: Michael
authors.initials: M
authors.lastname: France
authors.affiliation: Cardiovascular Trials Unit, The Old St Mary's Hospital, Hathersage Road, Oxford Road, Manchester M13 9WL, UK. sk7@doctors.org.uk.
authors.forename: See
authors.initials: S
authors.lastname: Kwok
authors.affiliation: Department of Medicine, Central Manchester Foundation Trust, Oxford Road, Manchester M13 9WL, UK. hsoran@aol.com.
authors.forename: Handrean
authors.initials: H
authors.lastname: Soran
authors.affiliation: Department of Imaging Science, University of Manchester, Oxford Road, Manchester M13 9PT, UK. steve.williams@manchester.ac.uk.
authors.forename: Steve
authors.initials: S
authors.lastname: Williams
authors.affiliation: Department of Medicine, Central Manchester Foundation Trust, Oxford Road, Manchester M13 9WL, UK. jan.ho@doctors.org.uk.
authors.forename: Jan Hoong
authors.initials: JH
authors.lastname: Ho
authors.affiliation: Department of Imaging Science, University of Manchester, Oxford Road, Manchester M13 9PT, UK. s.adam@doctors.org.uk.
authors.forename: Safwaan
authors.initials: S
authors.lastname: Adam
authors.affiliation: Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, UK. dexter.canoy@ceu.ox.ac.uk.
authors.forename: Dexter
authors.initials: D
authors.lastname: Canoy
authors.affiliation: School of Biomedicine, 3rd floor, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK. yifen.liu@manchester.ac.uk.
authors.forename: Yifen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Biomedicine, 3rd floor, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK. paul.durrington@manchester.ac.uk.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Durrington
mesh_terms: D000005:Abdomen / Q000000981:diagnostic imaging; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015992:Body Mass Index; D002570:Ceruloplasmin / Q000032:analysis*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005990:Glycerol / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008066:Lipolysis; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D014463:Ultrasonography
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D002570:Ceruloplasmin; D000410:Alanine Transaminase; D005990:Glycerol
keywords: NEFA; fatty liver; glycerol; insulin; lipolysis; magnetic resonance spectroscopy