Loss of regulation of lipogenesis in the Zucker diabetic rat. II. Changes in stearate and oleate synthesis.
De novo lipogenesis and dietary fat uptake are two major sources of fatty acid 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 Zucker diabetic fatty (ZDF) rats and their lean littermates (ZL) under two isocaloric dietary fat conditions. Lipogenesis was also determined using the deuterated water method. Conversion of palmitate to stearate and stearate to oleate was calculated from the deuterium incorporation by use of the 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 the dietary fat-to-carbohydrate ratio. The results suggest that suppression of fatty acid synthase and stearoyl-CoA desaturase activities is a normal adaptive mechanism to a 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 a 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.
Bassilian
Sara
S
Department of Pediatrics, Research and Education Institute, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
Ahmed
Syed
S
Lim
Shu K
SK
Boros
Laszlo G
LG
Mao
Catherine S
CS
Lee
W-N Paul
WN
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003903:Deuterium; D003920:Diabetes Mellitus / Q000378:metabolism*; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004822:Epididymis; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D008297:Male; D009765:Obesity; D019301:Oleic Acid / Q000096:biosynthesis*; D019308:Palmitic Acid / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D013229:Stearic Acids / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D014280:Triglycerides / Q000032:analysis / Q000097:blood
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005227:Fatty Acids; D008055:Lipids; D013229:Stearic Acids; D014280:Triglycerides; D019301:Oleic Acid; D019308:Palmitic Acid; C031183:stearic acid; D003903:Deuterium; D013230:Stearoyl-CoA Desaturase; D064429:Fatty Acid Synthases