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Effects of fatty acids on hepatic amino acid catabolism and fibrinogen synthesis in young healthy volunteers

¹Institute of Diabetes "Gerhardt Katsch" Karlsburg, D-17495 Karlsburg; ²Department of Clinical Pharmacology of the Peter Holtz Center of Pharmacology and Experimental Therapeutics, and ³Hospital Pharmacy, University of Greifswald, D-17487 Greifswald; and ⁴Department of Biochemistry and Physiology of Nutrition, German Institute of Human Nutrition, D-14558 Bergholz-Rehbrücke, Germany

Submitted 18 July 2002 ; accepted in final form 17 February 2003

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 -[¹³C]ketoisocaproic acid and [¹⁵N₂]urea enrichment values were measured with GC-MS. Plasma fibrinogen was isolated with the -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.

stable isotopes; fatty acids; leucine metabolism; urea production