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Title: HYPOTHALAMIC GENE EXPRESSION IN LEPTIN-TREATED LEAN AND OB/OB MICE

Author
item DELLA-FERA, MARY - UNIV. OF GEORGIA
item DUAN, JIUHUA - UNIV. OF GEORGIA
item CHOI, YANG-HO - UNIV. OF GEORGIA
item HARTZELL, DIANE - UNIV. OF GEORGIA
item Barb, Claude
item HAMRICK, MARK - UNIV. OF GEORGIA
item BAILE, CLIFTON - UNIV. OF GEORGIA

Submitted to: Society for Neuroscience Abstracts and Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/20/2005
Publication Date: 11/20/2005
Citation: Della-Fera, M.A., Duan, J., Choi, Y., Hartzell, D., Barb, C.R., Hamrick, M.W., Baile, C. 2005. Hypothalamic gene expression in leptin-treated lean and ob/ob mice [abstract]. Society for Neuroscience Abstracts and Proceedings. 35th Annual Meeting. p. 531.12.

Interpretive Summary:

Technical Abstract: Leptin-deficient ob/ob mice are more sensitive to exogenous leptin than lean mice and leptin treatment normalizes many of the phenotypic characteristics of ob/ob mice. We compared the effects of leptin treatment on hypothalamic gene expression in ob/ob and lean mice. Real-time Taqman™ RT-PCR (ABI Microfluidic cards) was used to quantitatively compare mRNA levels of selected hypothalamic genes in lean or ob/ob mice treated with vehicle (PBS) or leptin (10 µg/day) administered continuously for 14 days injection by subcutaneous miniosmotic pumps. Hypothalami were dissected and mRNA was extracted. Hypothalamic mRNA levels for ob/ob control mice were higher for AGRP (386.9%, P<.001), NPY (64.6%, P<.001), AVP (95.8%, P<.001), and TNF' (85.8%, P=.10), and lower for CART (15.6%, P<.05), CREB (23.7%, P<.01), JAK2 (17.6%, P<.05) and UCN3 (22.9%, P<.01) compared to lean controls. In leptin-treated ob/ob mice, hypothalamic NPY mRNA was reduced by 25.8% (P<.001), AGRP by 45% (P<.001), AVP by 32% (P<.001), and SOCS3 mRNA was increased by 32.1% compared to ob/ob controls (P<.05). In leptin-treated lean mice AGRP mRNA was increased by 28.3% compared to lean controls (P<.05). Hypothalamic NPY and AVP were strongly correlated in all samples (r=.83). Leptin treatment did not change CART mRNA level but dramatically upregulated POMC in both lean (8-fold increase, P<.01) and ob/ob mice (135-fold increase, P<.001). Leptin did not change levels of hypothalamic PTGES, TNF, OXT, SCT, VIP, GABRD, TH, MAPK, or STAT3 mRNA in either genotype. In conclusion, in ob/ob mice leptin treatment resulted in an mRNA profile similar to that of lean controls for many of the hypothalamic genes assessed; however, for some genes, eg., POMC, mRNA changes were much greater in ob/ob than in control mice. Supported in part by Georgia Research Alliance Eminent Scholar endowment held by CAB.