Postnatal feeding with high-fat diet induces obesity and precocious puberty in C57BL/6J mouse pups: a novel model of obesity and puberty

doi:10.1007/s11684-017-0530-y

Front. Med.

2017, Vol. 11

Issue (2) : 266-276 https://doi.org/10.1007/s11684-017-0530-y

RESEARCH ARTICLE

Postnatal feeding with high-fat diet induces obesity and precocious puberty in C57BL/6J mouse pups: a novel model of obesity and puberty

Rahim Ullah^1,², Yan Su^1,², Yi Shen², Chunlu Li², Xiaoqin Xu¹, Jianwei Zhang¹, Ke Huang¹, Naveed Rauf^1,², Yang He², Jingjing Cheng², Huaping Qin², Yu-Dong Zhou²(

), Junfen Fu¹(

)

¹. Department of Endocrinology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310051, China
². Department of Neurobiology, Institute of Neuroscience, and the Collaborative Innovation Center for Brain Science, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of Medicine, Hangzhou 310058, China

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Abstract

Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current study, we provided high-fat diet (HFD) to dams during lactation and to pups after weaning. We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity. Results showed that feeding with HFD induces fat deposition and obesity in pups. Furthermore, HFD more potently increased the body weight (BW) of male than female pups. HFD-fed female pups were obese, underwent precocious puberty, and showed increased kisspeptin expression in the hypothalamus. However, parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed litters with normal BW also exhibited precocious puberty. This finding suggested that diet composition but not BW triggers puberty onset. Our model suggests good construction validity of obesity and precocious puberty. Furthermore, our model can also be used to explore the mutual interactions between diet–induced postnatal childhood obesity and puberty.

Keywords postnatal HFD feeding obesity kisspeptin HPG axis precocious puberty

Corresponding Author(s): Yu-Dong Zhou,Junfen Fu

Just Accepted Date: 14 April 2017 Online First Date: 16 May 2017 Issue Date: 01 June 2017

Cite this article:

Rahim Ullah,Yan Su,Yi Shen, et al. Postnatal feeding with high-fat diet induces obesity and precocious puberty in C57BL/6J mouse pups: a novel model of obesity and puberty[J]. Front. Med., 2017, 11(2): 266-276.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0530-y
https://academic.hep.com.cn/fmd/EN/Y2017/V11/I2/266

Fig.1 Scheme for feeding of pups and dams.

Tab.1 Weight in grams of male and female pups at P-19 and P-24

Fig.2 Effects of HFD feeding on the mean±standard error of mean (SEM) weight gain in pups. HFD feeding significantly increased BW in P-19 (P<0.0001 for male and female) and P-24 (P<0.0001 for male and female) pups. Therefore, HFD feeding induces obesity in pups. C-C-C-C= control and C-C-H-H= HFD obese, M= male and F= female.

Tab.2 Weight in grams of male and female pups at P-40

Fig.3 Two-way ANOVA analysis revealed a significant interaction between diet (HFD vs. chow) (F= 134.5, P<0.001) and sex (male vs. female) (F= 165.1, P<0.001). HFD feeding significantly increased BW. Moreover, male pups were significantly heavier than female pups at P-40. In addition, as evident from the percent increase in BW, HFD more potently increases BW in male than female pups. C-C-H-H= HFD obese and C-C-C-C= control.

Fig.4 Effects of HFD feeding on mean±SEM increase in gonadal WAT in male pups (n = 4) at different time points. HFD feeding significantly increased (P = 0.0008 for P-19 and P = 0.0001 for P-24) WAT deposition in HFD-fed male pups. C-C-C-C= control, C-C-H-H= HFD obese, and M= male. HFD feeding increases WAT deposition.

Fig.5 Effects of HFD feeding on puberty onset (A) and weight gain (B). HFD feeding advances puberty onset (P<0.0001) and increases BW (P<0.0001) in female pups. C-C-C-C= control, C-C-H-H= HFD obese, and F= female.

Fig.6 Effect of HFD feeding on kisspeptin expression in the ARC of female pups at P-24. HFD significantly increases (P = 0.0005) kisspeptin expression in HFD-fed pups. C-C-C-C= control, C-C-H-H= HFD obese, and F= female. HFD feeding advances VC by increasing kisspeptin expression.

Fig.7 Difference between the BW (A) and age at puberty onset (B) of the H-H-H-H and C-C-H-H groups. H-H-H-H= HFD obese pups of parents that were already obese and underwent precocious puberty. C-C-H-H= HFD obese pups of normal parents. Parental obesity and precocious puberty show no synergistic effects on pups BW and puberty onset.

Tab.3 Weight in grams of female pups at the day of VC

Fig.8 BW of pups (n = 9 each group) at VC. C-C-H-H-L F has significantly lower BW (P<0.05) than C-C-H-H F and C-C-C-C F at the day of VC but still underwent precocious puberty at P-28. These results suggest that diet composition, not BW, affects puberty onset. C-C-H-H= obese fed on HFD; C-C-C-C= control; C-C-H-H-L= fed on HFD but with lower BW than obese and control groups.

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