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Am J Physiol Endocrinol Metab (November 6, 2001). doi:10.1152/ajpendo.00211.2001
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Articles in PresS, published online ahead of print November 5, 2001
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00211.2001
Submitted on May 15, 2001
Accepted on November 1, 2001

Loss of regulation of lipogenesis in the Zucker Diabetic (ZDF) rat, II: Changes in stearate and oleate synthesis

Sara Bassilian1, Syed Ahmed1, Shu K Lim1, Laszlo G Boros1, Catherine S Mao1, and Wai-Nang P Lee1*

1 Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA

* To whom correspondence should be addressed. E-mail: lee{at}gcrc.humc.edu.

De novo lipogenesis and dietary fat uptake are two major sources of fatty acids deposits in fat of obese animals. To determine the relative contribution of fatty acids from these two sources in obesity, we have determined the distribution of c16 and c18 fatty acids of triglycerides in plasma, liver and epididymal fat pad of ZDF rats and their lean litter-mates (ZL) under two isocaloric dietary fat conditions. Lipogenesis was also determined using deuterated water method. Conversion of palmitate to stearate and stearate to oleate were calculated from the deuterium incorporation using tracer dilution principle. In the ZL rat, lipogenesis was suppressed from 70% to 24%, conversion of palmitate to stearate from 86% to 78%, and conversion of stearate to oleate from 56% to 7% in response to an increase in dietary Fat/CHO ratio. The results suggest that suppression of fatty acid synthase and stearoyl-CoA desaturase activities is a normal adaptive mechanism to high fat diet. In contrast, de novo lipogenesis, chain elongation and desaturation were not suppressed by dietary fat in the ZDF rat. The lack of ability to adapt to high fat diet resulted in a higher plasma triglyceride concentration and excessive fat accumulation from both diet and de novo synthesis in the ZDF rat.




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