title: Greater dietary fat oxidation in obese compared with lean men: an adaptive mechanism to prevent liver fat accumulation?
abstract: Liver fat represents a balance between input, secretion, and oxidation of fatty acids. As humans spend the majority of a 24-h period in a postprandial state, dietary fatty acids make an important contribution to liver fat metabolism. We compared hepatic fatty acid partitioning in healthy lean (n = 9) and abdominally obese (n = 10) males over 24 h. Volunteers received three mixed meals adjusted for basal metabolic rate. U-13C-labeled fatty acids were incorporated into the meals, and [2H2]palmitate was infused intravenously to distinguish between sources of fatty acids incorporated into VLDL-TG. Immunoaffinity chromatography was used to isolate VLDL-TG of hepatic origin. Liver and whole body fatty acid oxidation was assessed by isotopic enrichment of 3-hydoxybutyrate and breath CO2. We found a similar contribution of dietary fatty acids to VLDL-TG in the two groups over 24 h. The contribution of fatty acids from splanchnic sources was higher (P < 0.05) in the abdominally obese group. Ketogenesis occurred to a significantly greater extent in abdominally obese compared with lean males, largely due to lessened downregulation of postprandial ketogenesis (P < 0.001). The appearance of 13C in breath CO2 was also greater (P < 0.001) in abdominally obese compared with lean men. Hepatic elongation and desaturation of palmitic acid were higher (P < 0.05) in abdominally obese than in lean males. Oxidation of dietary fatty acids and hepatic desaturation and elongation of palmitic acid occurred to a greater extent in abdominally obese men. These alterations may represent further pathways for redirection of fatty acids into export from the liver or oxidation to prevent liver fat accumulation.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. leanne.hodson@oxlip.ox.ac.uk
authors.forename: Leanne
authors.initials: L
authors.lastname: Hodson
authors.forename: Siobhán E
authors.initials: SE
authors.lastname: McQuaid
authors.forename: Sandy M
authors.initials: SM
authors.lastname: Humphreys
authors.forename: Ross
authors.initials: R
authors.lastname: Milne
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Fielding
authors.forename: Keith N
authors.initials: KN
authors.lastname: Frayn
authors.forename: Fredrik
authors.initials: F
authors.lastname: Karpe
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000378:metabolism; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism; D019540:Area Under Curve; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030087:lipoprotein triglyceride; D002097:C-Reactive Protein; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D020155:3-Hydroxybutyric Acid