Download PDF
Horm Metab Res 2002; 34(11/12): 686-690
DOI: 10.1055/s-2002-38264
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Effects of Fatty (fa) Allele and High-Fat Diet on Adipose Tissue Leptin and Lipid Metabolism

Y.-R.  Heo 1 , K.  Claycombe 2 , B.  H.  Jones 3 , P.  Wright 1 , G.  E.  Truett 1 , M.  Zemel 1 , W.  Banz 1 , M.  Maher 1 , N.  Moustaid-Moussa 1
  • 1 University of Tennessee, Department of Nutrition, Knoxville, TN, USA
  • 2 Michigan State University, Department of Food Science and Nutrition, MI, USA
  • 3 Life Science Division, Oak Ridge National Lab. Oak Ridge, TN, USA
Further Information

Publication History

Received 1 October 2002

Accepted after revision 26 November 2002

Publication Date:
27 March 2003 (online)

Also available at
    Permissions and Reprints

Abstract

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.

Key words

Obesity - Fatty Acid Synthase - Glycerol-3-Phosphate Dehydrogenase - Lipogenic Enzyme

References

  • 1 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese gene and its human homologue.  Nature. 1994;  372 425-432
    CrossrefPubMedGoogle Scholar
  • 2 Halaas J L, Gajiwala K S, Maffei M, Cohen S L, Chait B T, Rabinowitz D, Lallone R L, Burley S K, Friedman J M. Weight-reducing effects of the plasma protein encoded by the obese gene.  Science. 1995;  269 (5223) 543-546
    CrossrefPubMedGoogle Scholar
  • 3 Halaas J L, Gajiwala K S, Maffei M, Cohen S L, Chait B T, Rabinowitz D, Lallone R L, Burley S K, Friedman J M. Weight-reducing effects of the plasma protein encoded by the obese gene.  Science. 1995;  269 (5223) 543-546
    CrossrefPubMedGoogle Scholar
  • 4 Baskin D G, Seeley R J, Kuijper J L, Lok S, Weigle D S, Erickson J C, Palmiter R D, Schwartz M W. Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting.  Diabetes. 1998;  47 (4) 538-543
    PubMedGoogle Scholar
  • 5 Kastin A J, Pan W, Maness L M, Koletsky R J, Ernsberger P. Decreased transport of leptin across the blood-brain barrier in rats lacking the short form of the leptin receptor.  Peptides. 1999;  20 (12) 1449-1453
    CrossrefPubMedGoogle Scholar
  • 6 Takaya K, Ogawa Y, Isse N, Okazaki T, Satoh N, Masuzaki H, Mori K, Tamura N, Hosoda K, Nakao K. Molecular cloning of rat leptin receptor isoform complementary DNAs - identification of a missense mutation in Zucker fatty (fa/fa) rats.  Biochem Biophys Res Commun. 1996;  225 (1) 75-83
    CrossrefPubMedGoogle Scholar
  • 7 Cleary M P, Phillips F C. The presence of the “fa” gene in heterozygous (FA/fa) lean female rats, effects on body weight, body fat and serum leptin.  Obes Res. 1999;  7 (3) 293-298
    PubMedGoogle Scholar
  • 8 Maher M A, Banz W J, Truett G E, Zemel M B. Dietary fat and sex modify heterozygote effects of the rat fatty (fa) allele.  J Nutr. 1996;  126 2487-2493
    PubMedGoogle Scholar
  • 9 Reeves P G, Nielson F H, Fahey Jr. G C. AIN-93 purified diets for laboratory rodents: final report of American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet.  J Nutr. 1993;  123 (11) 1939-1951
    PubMedGoogle Scholar
  • 10 Moustaid N, Jones B H, Taylor J W. Insulin increases lipogenic enzyme activity in human adipocytes in primary culture.  J Nutr. 1996;  126 865-870
    PubMedGoogle Scholar
  • 11 Jones B H, Kim J H, Zemel M B, Woychik R P, Michaud E J, Wilkison W O, Moustaïd N. Upregulation of adipocyte metabolism by agouti protein: possible paracrine actions in yellow mouse obesity.  Am J Physiol. 1996;  270 E192-E196
    PubMedGoogle Scholar
  • 12 Turban S, Hainault I, Truccolo J, Andre J, Ferre P, Quignard-Boulange A, Guerre-Millo M. Specific increase in leptin production in obese (fa/fa) rat adipose cells.  Biochem J. 2002;  362 113-118
    CrossrefPubMedGoogle Scholar
  • 13 Jones B H, Kim J H, Zemel M B, Woychik R P, Michaud E J, Wilkison W O, Moustaïd N. Upregulation of adipocyte metabolism by agouti protein: possible paracrine actions in yellow mouse obesity.  Am J Physiol. 1996;  270 E192-E196
    PubMedGoogle Scholar
  • 14 Figlewicz D P, Dorsa D M, Stein L J, Baskin D G, Paquette T, Greenwood M R, Woods S C, Porte D. Brain and liver insulin binding is decreased in Zucker rats carrying the “fa” gene.  Endocrinol. 1985;  117 1537-1543
    PubMedGoogle Scholar
  • 15 Blonz E R, Stern J S, Curry D L. Dynamics of pancreatic insulin release in young Zucker rats: a heterozygote effect.  Am J Physiol. 1985;  248 (2 Pt. 1) E188-E193
    PubMedGoogle Scholar
  • 16 Wang M Y, Lee Y, Unger R H. Novel form of lipolysis induced by leptin.  J Biol Chem. 1999;  18 274 (25) 7541-7544
    PubMedGoogle Scholar
  • 17 Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis.  EMBO reports. 2001;  2 (4) 282-286
    CrossrefPubMedGoogle Scholar
  • 18 Soukas A, Cohen P, Socci N D, Friedman J M. Leptin-specific patterns of gene expression in white adipose tissue.  Genes Dev. 2000;  14 963-980
    PubMedGoogle Scholar
  • 19 Kim J B, Sarraf P, Wright M, Yao K M, Mueller E, Solanes G, Lowell B B, Spiegelman B M. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1.  J Clin Invest. 1998;  101 (1) 1-9
    CrossrefPubMedGoogle Scholar
  • 20 Unger R H, Orci L. Disease of liporegulation: new perspective on obesity and related disorders.  FASEB J. 2001;  15 312-321
    CrossrefPubMedGoogle Scholar
  • 21 York D, Holt S, Rothwell N, Stock M. Effect of age and gene dosage on brown adipose tissue of Zucker obese fa/fa rats.  Am J Physiol. 1984;  246 (5 Pt 1) E391-E396
    PubMedGoogle Scholar
  • 22 Phillips F C, Cleary M P. Metabolic measurements among homozygous (fa/fa) obese, heterozygous (Fa/fa) lean and homozygous (Fa/Fa) lean Zucker rat pups at 17 days of age.  J Nutr. 1994;  124 (8) 1230-1237
    PubMedGoogle Scholar
  • 23 Cleary M P, Phillips F C. Metabolic comparisons of 10-week-old obese (fa/fa) Zucker rats with both heterozygous (Fa/fa) and homozygous (FA/FA) lean rats.  Nutr Res. 1996;  16 1341-1352
    PubMedGoogle Scholar
  • 24 Lawrence V J, Coppack S W. The endocrine function of the fat cell-regulation by the sympathetic nervous system.  Horm Metab Res. 2000;  32 453-467
    PubMedGoogle Scholar

N. Moustaid-Moussa, Ph.D.

University of Tennessee · Nutrition Department ·

229 Jessie Harris Building · Knoxville · TN 37996-1920 · USA ·

Phone: + 1 (865) 974-6255

Fax: + 1 (865) 974-3491

Email: moustaid@utk.edu

      >