TY - JOUR
T1 - Effects of fatty (fa) allele and high-fat diet on adipose tissue leptin and lipid metabolism
AU - Heo, Y. R.
AU - Claycombe, K.
AU - Jones, B. H.
AU - Wright, P.
AU - Truett, G. E.
AU - Zemel, M.
AU - Banz, W.
AU - Maher, M.
AU - Moustaid-Moussa, N.
PY - 2002/11
Y1 - 2002/11
N2 - Leptin is an adipocyte-secreted hormone that binds hypothalamic receptors and potently decreases food intake. Leptin receptor defects in homozygous mutant Zucker fatty (fa/fa) rats lead to massive obesity, hyperphagia, decreased energy expenditure, and insulin resistance, while the phenotype of heterozygous (Fa/fa) lean rats lies between lean (Fa/Fa) and obese (fa/fa) rats. Whether heterezygotes exhibit specific changes in lipid metabolism in a diet-responsive manner is not clear. Thus, the specific aim of this study was to test whether the presence of one fa allele modulates lipid metabolism and leptin, and whether these effects are exacerbated by high-fat diet. We demonstrate that the presence of one fa allele significantly increases lipogenesis in adipose tissue assessed by glycerol-3-phosphate dehydrogenase (GPDH) and fatty acid synthase (FAS) activities. FAS is more responsive to high-fat diets than GPDH in Fa/fa rats. Adipose tissue leptin levels are significantly higher in fat pads of Fa/fa compared to Fa/Fa rats. Moreover, Fa/fa rats fed high-fat diet show an additional two-fold increase in leptin levels compared to wild type rats on the same diet. Collectively, these results indicate that the presence of one fa allele increase adipocyte lipogenic enzyme activities, which results in hyperleptinemia concurrent with increased adiposity.
AB - Leptin is an adipocyte-secreted hormone that binds hypothalamic receptors and potently decreases food intake. Leptin receptor defects in homozygous mutant Zucker fatty (fa/fa) rats lead to massive obesity, hyperphagia, decreased energy expenditure, and insulin resistance, while the phenotype of heterozygous (Fa/fa) lean rats lies between lean (Fa/Fa) and obese (fa/fa) rats. Whether heterezygotes exhibit specific changes in lipid metabolism in a diet-responsive manner is not clear. Thus, the specific aim of this study was to test whether the presence of one fa allele modulates lipid metabolism and leptin, and whether these effects are exacerbated by high-fat diet. We demonstrate that the presence of one fa allele significantly increases lipogenesis in adipose tissue assessed by glycerol-3-phosphate dehydrogenase (GPDH) and fatty acid synthase (FAS) activities. FAS is more responsive to high-fat diets than GPDH in Fa/fa rats. Adipose tissue leptin levels are significantly higher in fat pads of Fa/fa compared to Fa/Fa rats. Moreover, Fa/fa rats fed high-fat diet show an additional two-fold increase in leptin levels compared to wild type rats on the same diet. Collectively, these results indicate that the presence of one fa allele increase adipocyte lipogenic enzyme activities, which results in hyperleptinemia concurrent with increased adiposity.
KW - Fatty Acid Synthase
KW - Glycerol-3-Phosphate Dehydrogenase
KW - Lipogenic Enzyme
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=0036875502&partnerID=8YFLogxK
U2 - 10.1055/s-2002-38264
DO - 10.1055/s-2002-38264
M3 - Article
C2 - 12660883
AN - SCOPUS:0036875502
SN - 0018-5043
VL - 34
SP - 686
EP - 690
JO - Hormone and Metabolic Research
JF - Hormone and Metabolic Research
IS - 11-12
ER -