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Sex differences in the metabolic effects of diet-induced obesity vary by age of onset


Sex differences in the effect of diet-induced obesity (DIO) have been reported in juvenile mice. However, thorough side by side comparisons of the effects of DIO in males and females at different ages of onset have yet to be examined. We hypothesized that aged females would lose their protection, relative to males, from the effects of DIO. We examined the effect of DIO on body weight and glucose tolerance in juvenile, young adult, and middle-aged male and female mice. Our data show DIO in juvenile mice causes a greater increase in body weight and greater impairment in glucose tolerance in males than females. However, if the diet is initiated in young adult mice, these sex differences are absent. Further, if the diet is initiated in middle-aged mice, the sex difference is reversed, and females gain more weight and have greater impairment in glucose tolerance than males. Our data show that sex differences in the effect of DIO vary by age of onset; thus highlighting the importance of both age and sex as biological variables in DIO research.

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  1. Dakin RS, Walker BR, Seckl JR, Hadoke PW, Drake AJ. Estrogens protect male mice from obesity complications and influence glucocorticoid metabolism. Int J Obes. 2015;39:1539–47.

    Article  CAS  Google Scholar 

  2. Yang Y, Smith DL Jr., Keating KD, Allison DB, Nagy TR. Variations in body weight, food intake and body composition after long-term high-fat diet feeding in C57BL/6J mice. Obesity. 2014;22:2147–55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Atamni HJ, Mott R, Soller M, Iraqi FA. High-fat-diet induced development of increased fasting glucose levels and impaired response to intraperitoneal glucose challenge in the collaborative cross mouse genetic reference population. BMC Genet. 2016;17:10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Tester J, Sharma S, Jasik CB, Mietus-Snyder M, Tinajero-Deck L. Gender differences in prediabetes and insulin resistance among 1356 obese children in Northern California. Diabetes Metab Syndr. 2013;7:161–5.

    Article  PubMed  Google Scholar 

  5. Nishikawa S, Yasoshima A, Doi K, Nakayama H, Uetsuka K. Involvement of sex, strain and age factors in high fat diet-induced obesity in C57BL/6J and BALB/cA mice. Exp Anim. 2007;56:263–72.

    Article  PubMed  CAS  Google Scholar 

  6. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32:1431–7.

    Article  CAS  Google Scholar 

  7. Saltevo J, Kautiainen H, Vanhala M. Gender differences in adiponectin and low-grade inflammation among individuals with normal glucose tolerance, prediabetes, and type 2 diabetes. Gend Med. 2009;6:463–70.

    Article  PubMed  Google Scholar 

  8. Hong J, Stubbins RE, Smith RR, Harvey AE, Nunez NP. Differential susceptibility to obesity between male, female and ovariectomized female mice. Nutr J. 2009;8:11.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Grove KL, Fried SK, Greenberg AS, Xiao XQ, Clegg DJ. A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice. Int J Obes. 2010;34:989–1000.

    Article  CAS  Google Scholar 

  10. Johnson LA, Zuloaga KL, Kugelman TL, Mader KS, Morre JT, Zuloaga DG, et al. Amelioration of metabolic syndrome-associated cognitive impairments in mice via a reduction in dietary fat content or infusion of non-diabetic plasma. EBioMedicine. 2016;3:26–42.

    Article  PubMed  Google Scholar 

  11. Zuloaga KL, Johnson LA, Roese NE, Marzulla T, Zhang W, Nie X, et al. High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion. J Cereb Blood Flow Metab. 2016;36:1257–70.

    Article  PubMed  CAS  Google Scholar 

  12. Hwang L-L, Wang C-H, Li T-L, Chang S-D, Lin L-C, Chen C-P, et al. Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice. Obesity. 2010;18:463–9.

    Article  PubMed  CAS  Google Scholar 

  13. Knight EM, Martins IVA, Gümüsgöz S, Allan SM, Lawrence CB. High-fat diet-induced memory impairment in triple-transgenic Alzheimer’s disease (3xTgAD) mice is independent of changes in amyloid and tau pathology(). Neurobiol Aging. 2014;35:1821–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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The authors thank Dr. Yue Wang and David Riccio for their technical assistance and Dr. Lisa Robison for editing the manuscript.


This work was supported by American Heart Association Scientist Development Grant 12SDG2719002 (KLZ) and Albany Medical College start up funds (KLZ).

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Correspondence to Kristen L. Zuloaga.

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Salinero, A.E., Anderson, B.M. & Zuloaga, K.L. Sex differences in the metabolic effects of diet-induced obesity vary by age of onset. Int J Obes 42, 1088–1091 (2018).

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