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Upregulation of Lipogenic Transcripts in Association with the Development of Hyperphagia and Increased PPARγ Expression in Zucker Rats
Author(s) -
Truett Gary E,
Durham Holiday A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a167-c
Subject(s) - endocrinology , medicine , leptin , downregulation and upregulation , malic enzyme , insulin , adipose tissue , lipid metabolism , biology , enzyme , gene , obesity , dehydrogenase , biochemistry
Fatty rats develop hyperphagia on a single postnatal day, followed by expansion of adipose mass and increased insulin sensitivity, which may be related to a developmentally regulated increase in PPARγ expression. Inguinal adipose tissue RNA from +/+ and fa/fa rats at 20 days of age, before hyperphagia, and 24 days of age, after onset of hyperphagia, was hybridized to Affymetrix GeneChips to identify differentially expressed transcripts. Expression of transcripts in lipid metabolism were measured by RTPCR for validation. Fatty acid synthase, farnesyl diphosphate synthase, malic enzyme, transketolase, and glycerol 3‐phosphate acyltransferase were induced several‐fold in fatties after the onset of hyperphagia, but not before the onset of hyperphagia. Insulin induced gene 1 (insig‐1), a marker of insulin signaling, was induced in fatties after the onset of hyperphagia, but not before. In contrast, leptin and LPL were already induced (2.6‐ and 3.3‐fold) prior to the onset of hyperphagia. Stearoyl CoA desaturase (SCD) was upregulated 10.6‐fold prior to the onset of hyperphagia. Leptin, LPL and SCD are likely to be affected by leptin signaling at this age independent of insulin. PPARγ was expressed at low levels in both wildtypes and fatties before the onset of hyperphagia and doubled from 20 to 24 days of age in both genotypes. PPARγ expression was 1.7‐fold higher in fatties at both ages. The induction of PPARγ at this age is a developmentally regulated event that may contribute to the emergence of hyperphagia in fatties.