24. BROWN ADIPOSE TISSUE: AN EARLY MARKER OF METABOLIC SYNDROME?

Department: Bioengineering
Faculty Advisor(s): Morton P. Printz | Geert Schmid-Schönbein

Primary Student
Name: Joanna Lyn Thomas
Email: j1thomas@ucsd.edu
Phone: 858-534-2596
Grad Year: 2009

Abstract
As the occurrence of metabolic syndrome becomes more and more commonplace at a younger and younger age the need for genetic markers, a means to detect susceptibility at an early age, grows. In recent years, with an improved understanding of the relationship between endocrine organs and metabolic regulation, researchers have targeted adipose tissue for clues to metabolic syndrome, but the role of brown adipocytes, distinguished by mulit-locular lipid vacuoles, round nuclei, and numerous mitochondria, beyond thermogenesis is not well understood. After an initial observation that expression of the brown adipose tissue (BAT) specific gene, UCP1, differed significantly in kidney BAT (KBAT) from 4 week old normotensive (BN-Lx) and hypertensive (SHR) rats, the KBAT and interscapular BAT (IBAT) from 4 week old BN-Lx, SHR, and eight recombinant inbred (RI) strains (derived from the F2 generation of a BN-Lx-SHR crossing) were analyzed for morphological and genetic differences. Aortic (ABAT) from 4 week old BN-Lx and SHR was also included in the morphology and gene expression studies. In all three types of BAT, images of 10um sections revealed dramatic differences between SHR and BN-Lx. Average lipid droplet cross sectional area in the KBAT from the 10 strains was found to strongly correlate with adult dark systolic blood pressure (p = .0013); no correlation was found in IBAT. Semi-quantitative RT-PCR and western blots for UCP1, slc6a2 (norepinephrine transporter), Beta3-adrenergic receptor, and adenylyl cyclase III showed on average a 7-fold greater expression in brown adipose tissues from BN-Lx compared to SHR. Electron microscope images of BN-Lx and SHR KBAT and IBAT mitochondria indicate wide-spread abnormalities in the structure of SHR IBAT mitochondria, such as swollen matrix and vesiculation of cristae. The major structural and genetic differences found in the SHR brown adipose depots prior to the development of measurable hypertension would suggest brown adipose tissue may be able to offer us insight into the etiology of metabolic syndrome or, in fact, may harbor a genetic marker of metabolic syndrome.

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