Reciprocal hemizygosity analysis of mouse hepatic lipase reveals influence on obesity

Poupak Farahani, Janis S. Fisler, Howard Wong, Adam L. Diament, Nengjun Yi, Craig H Warden

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Objectives: We previously demonstrated coincident quantitative trait loci (QTLs) for percentage body fat, plasma hepatic lipase (HL) activity, and plasma cholesterol on mouse chromosome 7. In the present study, we investigated whether hepatic lipase (Lipc) is an obesity gene, whether Lipc interacts with an unknown gene on chromosome 7, and how HL activity is linked to the chromosome 7 locus. Research Methods and Procedures: BSB mice are a model of complex obesity due to interactions among genes from C57BL/6J and Mus spretus (SPRET) in (C57BL/6J X SPRET) X C57BL/6J backcross mice. Five crosses tested the impact on obesity of combinations of inactive (knockout) and wild-type Lipc alleles from C57BL/6J or SPRET in a reciprocal hemizygosity analysis. Results: The combined data from this allelic series suggest that Lipc alleles, and not alleles from a gene linked to Lipc, influence obesity. No interaction between Lipc and chromosome 7 was demonstrated. We confirmed the chromosome 7 QTLs for obesity, HL activity, and cholesterol. Because obesity and HL activity are not consistently associated in the BSB model, linkage of HL activity to chromosome 7 is not secondary to obesity per se. We also report, for the first time to our knowledge, a QTL in mammals for food intake. Discussion: This use of reciprocal hemizygosity analysis in mammals, which, to our knowledge, is the first reported, reveals its power to detect previously unknown effects of Lipc on obesity.

Original languageEnglish (US)
Pages (from-to)292-305
Number of pages14
JournalObesity Research
Volume12
Issue number2
StatePublished - 2004

Keywords

  • Cholesterol
  • Food intake
  • Genetics
  • Hepatic lipase activity
  • Percentage body fat

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

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    Farahani, P., Fisler, J. S., Wong, H., Diament, A. L., Yi, N., & Warden, C. H. (2004). Reciprocal hemizygosity analysis of mouse hepatic lipase reveals influence on obesity. Obesity Research, 12(2), 292-305.