Date of Award

5-2005

Degree Type

Thesis

Degree Name

Master of Science

Major

Nutrition

Major Professor

Gary E. Truett

Committee Members

Jung Han Kim, James Bailey

Abstract

The Zucker fatty (fa/fa) rat inherits a defective leptin receptor with impaired leptin signaling. Fatties grow at the same rate as their littermates for the first 22 days of age, and then suddenly begin to grow at a much higher rate. This corresponds with the emergence of robust hyperphagia in the fatty rat and leads to overt obesity within days. This striking change in energy balance regulation makes it possible to determine which sets of genes are regulated by the fatty mutation before and after the onset of hyperphagia. Genechip microarrays were used to screen inguinal adipose tissue mRNA from wildtype and fatty rats at 20 days of age (before the emergence of hyperphagia) and 24 days of age (after the emergence of hyperphagia). Differentially expressed transcripts from several pathways were validated by real time quantitative reverse transcription polymerase chain reaction (RT-PCR). Transcripts associated with lipogenic pathways, including fatty acid synthase, malic enzyme, transketolase, glycerol 3-phosphate acyltransferase, insulin induced gene 1, and farnesyl diphosphate synthase, were expressed at similar levels in wildtypes and fatty rats before the onset of hyperphagia, but were highly induced in fatty rats after the onset of hyperphagia. A notable exception was stearoyt CoA desaturase 1, which converts saturated fatty acids synthesized by tipogenic pathways into monounsaturated fatty acids. Scd1 was upregulated in fatties 10.6-fold before hyperphagia emerged, and after the onset of hyperphagia, SCD1 expression increased 5.7-fold in fatty rats. This suggests that Scd1 is regulated independent of lipogenesis before the onset of hyperphagia, but is also developmentally upregulated. Leptin, lipoprotein lipase and PPARy mRNAs were also elevated prior to the onset of hyperphagia and may share a common regulatory pathway with stearoyl CoA desaturase 1.

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