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Int J Clin Exp Pathol 2013;6(8):1574-1584

Original Article
Butyrate alleviates metabolic impairments and protects pancreatic β cell function in
pregnant mice with obesity

Hua-Ping Li, Xuan Chen, Ming-Qing Li

Department of Gynecology & Obstetrics, the 6th People’s Hospital affiliated to Shanghai Jiaotong University, Shanghai 6th People’s Hospital,
Shanghai 200233, China; Department of Gynecology & Obstetrics, the first people’s Hospital of Wujiang District of Suzhou City, Suzhou
215200, China; Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai
Medical College, Shanghai, 200011, China. These authors contribute equally to this work.

Received June 18, 2013; Accepted July 8, 2013; Epub July 15, 2013; Published August 1, 2013

Abstract: The relative or absolute deficiency of pancreatic β-cell mass function underlies the pathogenesis of diabetes. It is necessary to
alleviate the metabolic stress and reduce the demand for insulin to decrease the effects of mutations affecting β-cell expansion. Butyrate is a
natural nutrient existed in food and can also be produced physiologically through the intestinal fermentation of fiber. Pregnancy and obesity
model would be helpful for understanding how β-cell adapt to insulin resistance and how butyrate alleviate the metabolic impairment and
protect pancreatic β cell function in pregnant mice with obesity. C57BL/6J female mice were divided into three groups and fed with high fat food
(HF group, 40% energy from fat), high fat with sodium butyrate food (HSF group, 95% HF with 5% butyrate), or control food (CF group, 14%
energy from fat), respectively. The feeding would last for 14 weeks before mating and throughout the gestation period. A subset of dams were
sacrificed at gestational day (GD) 14.5 to evaluate the changes of metabolism and β-cell function, mass, proliferation and apoptosis,
inflammatory reaction of islet from different diet. Pancreases were double immuno-labeled to assess the islet morphology, insulin expression,
expression of proliferation gene PCNA and anti-apoptosis gene bcl-2. Moreover, we detected the expression of NF-κB, phosphorylated NF-κB
(pNF-κB) to evaluate the islet inflammatory response with immunohistochemistry. Mice fed with HSF showed obviously changes including the
decreased values of weight gain, glucose, insulin, triglyceride and total cholesterol level of blood compared with high fat diet group, and the
reduced circulating maternal pro-inflammation factors at GD14.5. Mice fed with HF displayed β-cell hyperplasia with a greater β-cell size and β-
cell area in pancreas. Furthermore, the higher ratio of apoptosis and inflammatory response were found in HF group compared with HSF and
CF group, while the proliferation rates of β-cell increased in HF group, but not in HSF or CF. Butyrate shows an obvious function of anti-obesity,
and can alleviate the metabolic stress, maintain the β-cell function and protect them from inflammatory response in pregnant obese mouse
without obvious fetus toxicity. (IJCEP1306012).

Keywords: Sodium butyrate, β-cell, pancreatic islet, diabetes, GDM

Address correspondence to: Dr. Hua-Ping Li, Department of Gynecology & Obstetrics, the 6th People’s Hospital affiliated to Shanghai
Jiaotong University, Shanghai 6th People’s Hospital, No.600, Yishan Road, Shanghai 200233, China. Tel: 86-21-64369181; E-mail:
hpli819@sohu.com Or Dr. Ming-Qing Li, Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan
University Shanghai Medical College, No.413, Zhaozhou Road, Shanghai 200011, China. Phone: 86-21-63457331; E-mail: mqli1311@yahoo.
com.cn