Effects of fatty acids on hepatic amino acid catabolism and fibrinogen synthesis in young healthy volunteers.
Increased synthesis rate of fibrinogen, an independent risk factor for cardiovascular disease, was recently reported in obese insulin-resistant female adolescents with chronic elevated nonesterified fatty acids (NEFA). It is unknown whether a short-term change of NEFA concentrations controls hepatic fibrinogen synthesis. Therefore, 10 healthy male volunteers (24.5 +/- 3.3 yr, body mass index 23.5 +/- 2.9 kg/m2) were investigated in random order under basal and elevated NEFA for 8 h. Leucine metabolism, the fractional synthesis rates (FSR) of plasma fibrinogen, and endogenous urea production rates were measured during primed, continuous infusion of [1-13C]leucine and [15N2]urea, respectively. Plasma alpha-[13C]ketoisocaproic acid and [15N2]urea enrichment values were measured with GC-MS. Plasma fibrinogen was isolated with the beta-alanine method, and fibrinogen-related [13C]leucine enrichment was analyzed by GC-CIRMS. Lipofundin infusion and subcutaneous heparin tripled NEFA and triglycerides in the tests. Plasma glucose, circulating insulin, human C-peptide, and plasma glucagon were not changed by the study procedure. Fibrinogen FSR were significantly lower in tests with NEFA elevation (18.44 +/- 4.67%) than in control tests (21.48 +/- 4.32%; P < 0.05). Plasma fibrinogen concentrations measured were not significantly different (NEFA test subjects: 1.85 +/- 0.33, controls: 1.97 +/- 0.54 g/l). Parameters of leucine metabolism, such as leucine rate of appearance, leucine oxidation, and nonoxidative leucine disposal, were not influenced by NEFA elevation, and endogenous urea production remained unchanged. NEFA contributes to short-term regulation of fibrinogen FSR in healthy volunteers under unchanged hormonal status, leucine metabolism, and overall amino acid catabolism. Its contribution might be of relevance at least after fat-rich meals, counteracting by reduction of FSR the blood viscosity increase implied by hyperlipidemia.
Freyse
Ernst-Joachim
EJ
Institut für Diabetes "Gerhardt Katsch" Karlsburg, Germany. diab@mail.uni-greifswald.de
Giessmann
Thomas
T
Petzke
Klaus Jürgen
KJ
Knospe
Siegfried
S
Engel
Georg
G
Heinke
Peter
P
Metges
Cornelia C
CC
Siegmund
Werner
W
D000328:Adult; D000465:Algorithms; D000596:Amino Acids / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D005340:Fibrinogen / Q000096:biosynthesis*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006400:Hematocrit; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007651:Keto Acids / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000378:metabolism
D000596:Amino Acids; D001786:Blood Glucose; D005227:Fatty Acids; D005343:Fibrinolytic Agents; D007651:Keto Acids; D014280:Triglycerides; D002245:Carbon Dioxide; C013082:alpha-ketoisocaproic acid; D014508:Urea; D005340:Fibrinogen; D006493:Heparin; D007930:Leucine