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Linking cellular zinc status to body weight and fat mass: mapping quantitative trait loci in Znt7 knockout mice

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Abstract

Zinc transporter 7 (Znt7, Slc30a7) knockout (KO) mice display abnormalities in body weight gain and body adiposity. Regulation of body weight and body fat accumulation is complex, involving multiple genetic and environmental factors. To understand how zinc homeostasis influences body weight and fat deposit and to identify quantitative trait loci (QTLs) that link zinc metabolism to growth and adiposity, we conducted a genome-wide mapping study using male F2 Znt7 KO mice and wild-type (WT) littermates with a mixed 129P1/ReJ and C57BL/6J genetic background. The mice were fed a semi-purified diet containing 30-mg Zn/kg diet at weaning. Body weights and fat pad weights including epididymal, retroperitoneal, and femoral subcutaneous fat pads were measured at 16 weeks of age. We detected two significant QTLs (p < 0.05) for body weight and fat deposit. One was in the F2 Znt7 KO population and the other in the F2 WT population. In Znt7 KO mice, the body weight and fat deposit was significantly linked to a locus on chromosome 7 ranging from 64.3 to 78.3 Mb. In WT mice, a significant linkage of retroperitoneal fat mass was found on chromosome 8 between 14.5 and 63.5 Mb. In addition, several other suggestive QTLs (p < 0.63) for body weight and fat accumulation were detected in Znt7 KO and WT mice. In conclusion, the QTLs identified in this study may provide new hints to uncover the genes linking cellular zinc status to growth and body fat accumulation.

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Acknowledgments

We thank Dr. Craig H. Warden, Department of Pediatrics at UC Davis, for helpful comments and suggestions during the study. We thank the research scientists in the Obesity and Metabolism Research Unit, Western Human Nutrition Research Center, for the helpful discussion and support. This work was supported by the United States Department of Agriculture, ARS intramural projects 5306-515-30-014-00D and 5306-515-20-007-00D. USDA is an equal opportunity provider and employer.

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Authors and Affiliations

  1. Integrative Genetics and Genomics Graduate Group, University of California Davis, One Shields Avenue, Davis, CA, 95616, USA

    Surapun Tepaamorndech

  2. Obesity and Metabolism Research Unit, USDA/ARS/Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA, 95616, USA

    Catherine P. Kirschke & Liping Huang

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  1. Surapun Tepaamorndech
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Correspondence to Liping Huang.

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Supplemental Fig. 1

Linear regression of age on body weight. Mice including Znt7 KO and WT were fasted at ~07:00 for 4 h. Body weights (fasted) were recorded. Linear regression of age on body weight was performed using GraphPad Prism (GraphPad Software, Inc., La Jolla, CA). R 2 is the coefficient of determination which indicates that age variants (in the number of days) at the necropsying time around 16 weeks of age were not associated with the difference in body weights observed in both Znt7 KO and WT groups (p > 0.05)

Supplemental Fig. 2

Amino acid sequence alignment of the orthologues of Mboat4. The Mboat4 amino acid sequences from the mouse and human proteins are boxed. The protein alignment was obtained by BLAST hits with the mouse Mboat4 protein sequence using SIFT Blink (http://sift.jcvi.org/) (Ng and Henikoff 2003). The isoleucine residues (P) in the orthologues that align with the amino acids at position 31 in the mouse Mboat4 protein (B6) are shaded in gray. The phenylalanine residue (F) at the position 53 in the mouse Mboat4 protein (B6) was also shaded in gray. The leucine residues (L) that are conserved between 129P1 and other Mboat 4 orthologues are circled

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Tepaamorndech, S., Kirschke, C.P. & Huang, L. Linking cellular zinc status to body weight and fat mass: mapping quantitative trait loci in Znt7 knockout mice. Mamm Genome 25, 335–353 (2014). https://doi.org/10.1007/s00335-014-9512-4

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