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Genetics of leptin expression in baboons

Abstract

OBJECTIVE: Leptin gene expression is higher in females than in males, and is regulated by many factors including energy intake and insulin, but little is known about the inheritance of leptin gene expression. We have investigated leptin (LEP) gene express-ion, to determine whether it is heritable, and whether the difference in LEP expression between males and females has a genetic component.

STUDY POPULATION: A total of 319 baboons (Papio hamadryas) (220 females, 99 males) from a captive, pedigreed colony.

MEASUREMENTS AND METHODS: We cloned a baboon LEP cDNA, and quantified LEP mRNA expression in baboon omental adipose tissue using a ribonuclease protection assay. In addition, we assayed circulating leptin levels, adipocyte cell volume, and weight. We used maximum likelihood-based variance decomposition methods to determine the genetic architecture of LEP levels, including testing for genotype-by-sex interaction.

RESULTS: Omental LEP mRNA expression was significantly and positively correlated with weight and adipocyte cell volume in baboons. Both mRNA and plasma levels of leptin were higher in females than in males, and both measures were heritable. The results of our genetic analysis show that there was a genotype-by-sex interaction in the levels of plasma leptin, but not in omental LEP mRNA.

CONCLUSIONS: As in humans, baboon leptin mRNA and protein levels are expressed at a higher level in females than in males. We detected evidence that the plasma levels were affected by genes that are differentially expressed in males and females, while the omental mRNA levels were not. This finding suggests that the genes that differentially regulate plasma leptin levels between males and females may exert their effects on post-transcriptional processes.

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References

  1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–432.

    Article  CAS  Google Scholar 

  2. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O'Rahilly S . Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903–908.

    Article  CAS  Google Scholar 

  3. Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD . A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998; 18: 213–215.

    Article  CAS  Google Scholar 

  4. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, Kern PA, Friedman JM . Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995; 1: 1155–1161.

    Article  CAS  Google Scholar 

  5. Frederich RC, Lollmann B, Hamann A, Napolitano-Rosen A, Kahn BB, Lowell BB, Flier JS . Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. J Clin Invest 1995; 96: 1658–1663.

    Article  CAS  Google Scholar 

  6. Frühbeck G, Jebb SA, Prentice AM . Leptin: physiology and pathophysiology. Clin Physiol 1998; 18: 399–419.

    Article  Google Scholar 

  7. Havel PJ, Townsend R, Chaump L, Teff K . High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes 1999; 48: 334–341.

    Article  CAS  Google Scholar 

  8. Sinha MK . Human leptin: the hormone of adipose tissue. Eur J Endocrinol 1997; 136: 461–464.

    Article  CAS  Google Scholar 

  9. Havel PJ . Mechanisms regulating leptin production: implications for control of energy balance. Am J Clin Nutr 1999; 70: 305–306.

    Article  CAS  Google Scholar 

  10. Rosenbaum M, Nicolson M, Hirsch J, Heymsfield SB, Gallagher D, Chu F, Leibel RL . Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab 1996; 81: 3424–3427.

    CAS  Google Scholar 

  11. Havel PJ, Kasim-Karakas S, Dubuc GR, Mueller W, Phinney SD . Gender differences in plasma leptin concentrations. Nat Med 1996; 2: 949–950.

    Article  CAS  Google Scholar 

  12. Montague CT, Prins JB, Sanders L, Digby JE, O'Rahilly S . Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. Diabetes 1997; 46: 342–347.

    Article  CAS  Google Scholar 

  13. Martin LJ, Mahaney MC, Almasy L, MacCluer JW, Blangero J, Jaquish CE, Comuzzie AG . Leptin's sexual dimorphism results from genotype by sex interactions mediated by testosterone. Obes Res 2002; 10: 14–21.

    Article  CAS  Google Scholar 

  14. Comuzzie AG, Cole SA, Martin LJ, Carey KD, Mahaney MC, Blangero J, VandeBerg JL . The baboon as a non-human primate model for the study of the genetics of obesity. Obes Res 2003; 11: 75–80.

    Article  Google Scholar 

  15. Williams-Blangero S, VandeBerg JL, Blangero J, Konigsberg L, Dyke B . Genetic differentiation between baboon subspecies: relevance for biomedical research. Am J Primatol 1990; 20: 67–81.

    Article  Google Scholar 

  16. Lewis DS, Bertrand HA, McMahan CA, McGill Jr HC, Carey KD, Masoro EJ . Preweaning food intake influences the adiposity of young adult baboons. J Clin Invest 1986; 78: 899–905.

    Article  CAS  Google Scholar 

  17. Chomczynski P . A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 1993; 15: 532–535.

    CAS  PubMed  Google Scholar 

  18. Masuzaki H, Ogawa Y, Isse N, Satoh N, Okazaki T, Shigemoto M, Mori K, Tamura N, Hosoda K, Yoshimasa Y, Jingami H, Kawada T, Nakao K . Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes 1995; 44: 855–858.

    Article  CAS  Google Scholar 

  19. Cole SA, Hixson JE . Baboon lipoprotein lipase: cDNA sequence and variable tissue-specific expression of two transcripts. Gene 1995; 161: 265–269.

    Article  CAS  Google Scholar 

  20. Almasy L, Blangero J . Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 1998; 62: 1198–1211.

    Article  CAS  Google Scholar 

  21. Hopper JL, Mathews JD . Extensions to multivariate normal models for pedigree analysis. Ann Hum Genet 1982; 46: 373–383.

    Article  CAS  Google Scholar 

  22. Lange K, Boehnke M . Extensions to pedigree analysis. IV. Covariance components models for multivariate traits. Am J Med Genet 1983; 14: 513–524.

    Article  CAS  Google Scholar 

  23. Comuzzie AG, Blangero J, Mahaney MC, Mitchell BD, Stern MP, MacCluer JW . The quantitative genetics of sexual dimorphism in body fat measurements. Am J Hum Biol 1993; 5: 725–734.

    Article  Google Scholar 

  24. Self SG, Liang KY . Asymptotic properties of maximum likelihood ratio tests under nonstandard conditions. J Am Stat Assoc 1987; 82: 605–610.

    Article  Google Scholar 

  25. Hotta K, Gustafson TA, Ortmeyer HK, Bodkin NL, Nicolson MA, Hansen BC . Regulation of obese (ob) mRNA and plasma leptin levels in rhesus monkeys. Effects of insulin, body weight, and non-insulin-dependent diabetes mellitus. J Biol Chem 1996; 271: 25327–25331.

    Article  CAS  Google Scholar 

  26. Comuzzie AG, Hixson JE, Almasy L, Mitchell BD, Mahaney MC, Dyer TD, Stern MP, MacCluer JW, Blangero J . A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. Nat Genet 1997; 15: 273–276.

    Article  CAS  Google Scholar 

  27. Zhang Y, Guo KY, Diaz PA, Heo M, Leibel RL . Determinants of leptin gene expression in fat depots of lean mice. Am J Physiol Regul Integr Comp Physiol 2002; 282: R226–R234.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Mary Sparks and the support staff of the Department of Physiology and Medicine at the Southwest Foundation for Biomedical Research for their assistance with the fat biopsies. This research was supported by NIH Grants P01 HL28972, P51 RR13986, and a grant from the Kronkosky Charitable Foundation to SAC.

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Correspondence to S A Cole.

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Cole, S., Martin, L., Peebles, K. et al. Genetics of leptin expression in baboons. Int J Obes 27, 778–783 (2003). https://doi.org/10.1038/sj.ijo.0802310

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