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Animal Models

Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery

International Journal of Obesity volume 39, pages 798–805 (2015)Cite this article

Subjects

Abstract

Objective:

Weight regain contributes to the therapeutic failure in 15–20% of type 2 diabetic patients after Roux-en-Y gastric bypass surgery (RYGB), and the mechanism remains largely unknown. This study was conducted to explore the mechanism of weight regain.

Research design:

Wild-type (WT) diet-induced obese (DIO) mice were used to mimic human obesity, and ob/ob mice were used for leptin deficiency-induced obesity. Two groups of mice were compared in weight regain for 10 months after RYGB. Weight loss, food intake, fecal energy loss and energy expenditure were monitored in the study of weight regain. Fasting insulin, insulin tolerance and homeostatic model assessment-insulin resistance were tested for insulin sensitivity under the weight regain. Weight loss from RYGB and calorie restriction was compared for the impact in insulin sensitivity.

Results:

In WT mice, RYGB induced a sustained weight loss and insulin sensitization over the sham operation in this 10-month study. However, RYGB failed to generate the same effects in leptin-deficient ob/ob mice, which suffered a weight regain over the pre-surgery level. In ob/ob mice, body weight was reduced by RYGB transiently in the first week, recovered in the second week and increased over the baseline thereafter. Weight loss was induced by RYGB relative to that of sham mice, but the loss was not sufficient to keep body weight below the pre-surgery levels. In addition, insulin sensitivity was not improved by the weight loss. The response to RYGB was improved in ob/ob mice by 2 weeks of leptin treatment. Weight loss from calorie restriction had an equivalent effect on insulin sensitization compared with that of RYGB.

Conclusion:

Those data demonstrate that ob/ob mice and DIO mice responded differently to RYGB surgery, suggesting that leptin may be one of the factors required for RYGB to prevent weight regain and diabetes recurrence.

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Acknowledgements

This study is supported by the National Institutes of Health research projects DK085495 and DK068036 (ZH and JY), DK047348 (HRB), DK072476 (HM), F32-DK097896 (KRZ), COBRE (NIH P20-RR021945) and CNRU (NIH 1P30-DK072476) center grants (Cell Biology and Bio-imaging Core facilities).

Author Contributions

ZH, KR-Z, CD, RAM and HL, performed the experiments. HM, MK, H-RB and JY designed the study and wrote the manuscript. JY is fully responsible for this article. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    Z Hao, H Münzberg, K Rezai-Zadeh, H-R Berthoud & J Ye

  2. Louisiana State University Agricultural Center, Baton Rouge, LA, USA

    M Keenan & D Coulon

  3. Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China

    H Lu

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  1. Z Hao
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Correspondence to J Ye.

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Hao, Z., Münzberg, H., Rezai-Zadeh, K. et al. Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery. Int J Obes 39, 798–805 (2015). https://doi.org/10.1038/ijo.2014.189

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