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Am J Physiol Endocrinol Metab (December 4, 2001). doi:10.1152/ajpendo.00412.2001
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Articles in PresS, published online ahead of print December 4, 2001
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00412.2001
Submitted on September 17, 2001
Accepted on November 28, 2001

Increased Synthesis Rate of Fibrinogen as a Basis for its Elevated Plasma Levels in Obese Female Adolescents

Prabhakaran Balagopal1*, Shawn Sweeten1, and Nelly Mauras2

1 Research, Nemours Children's Clinic, Jacksonville, Florida, USA
2 Endocrinology, Nemours Children's Clinic, Jacksonville, Florida, USA

* To whom correspondence should be addressed. E-mail: bbalagopal{at}nemours.org.

Increased concentrations of plasma fibrinogen (an independent risk factor for cardiovascular disease, CVD) in obese children have been reported. The underlying mechanism for this, however, remains to be defined. In the current study we measured the fractional synthesis rates (FSR) of plasma fibrinogen in six healthy, post-pubertal obese girls (body mass index, BMI =36.6±1.8 kg.m-2; Age =16.6±0.5 years) and six age-matched lean normal control girls (BMI = 20.8±0.7kg.m-2; Age =16.4±0.4 years) during a primed, continuous infusion of L-[1-[13C]leucine in the post-absorptive state. The method involved purification of plasma fibrinogen using immuno-affinity chromatography followed by measurement of [13C]leucine enrichment using Gas Chromatography - Combustion - Isotope Ratio Mass Spectrometry. The FSR of fibrinogen in obese girls (35.06±2.61%.day-1) was almost double that in lean girls (17.02±1.43%.day-1) and this increase was associated with a relative increase in plasma concentration of fibrinogen as well as BMI in the subjects studied. Obese subjects had high fasting insulin levels (138 ±47 pmol.L-1) compared to that in lean subjects (54 ±11 pmol.L-1), whereas their glucose concentrations were similar (4.5±0.3 mmol.L-1 in obese and 4.4±0.4 mmol.L-1 in lean subjects), suggesting insulin resistance. The doubling of the FSR of fibrinogen provides novel insight into the mechanism of elevated levels of plasma fibrinogen and suggests a primary role for increased synthesis in producing the hyperfibrinogenemia associated with obesity. This finding may have important implications in the design of therapies for modulating plasma fibrinogen levels in obesity and /or CVD in childhood.




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