Hypertriglyceridemia in female rats during pregnancy induces obesity in male offspring via altering hypothalamic leptin signaling

// Tanzil Ur Rahman 1, 2, * , Kamran Ullah 1, 2, * , Zhang-Hong Ke 4 , Meng-Xi Guo 1, 2 , Lu-Yang Jin 1, 2 , Jun Ren 1, 2 , Yu-Zhong Zhou 1, 2 , Yi Cheng 1, 2 , Xin-Yan Dong 1, 2 , Hai-Yan Pang 1, 2 , Ting-Ting Wang 1 , Jian-Zhong Sheng 1, 2, 3 and He-Feng Huang 1, 3 1 The Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China 2 Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China 3 The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 4 Center of Reproductive Medicine, Fujian Maternity and Children Health Hospital, Fujian Medical University, Fuzhou, China * These authors have contributed equally to this work Correspondence to: Jian-Zhong Sheng, email: shengjz@zju.edu.cn He-Feng Huang, email: huanghefg@hotmail.com Keywords: triglyceridemia, leptin, hypothalamus, neuropeptide Y, pSTAT3 Received: February 08, 2017 Accepted: May 10, 2017 Published: June 16, 2017 ABSTRACT Maternal obesity influence the child’s long-term development and health. Though, the mechanism concerned in this process is still uncertain. In the present study, we explored whether overfeeding of a high-fat diet during pregnancy in female rats altered metabolic phenotypes in an F1 generation and authenticated the contribution of hypothalamic leptin signaling. Leptin responsiveness and the number of immunopositive neurons for phosphorylated signal transducer and activator transcription 3 (pSTAT3) were analyzed. Neuropeptide Y in the arcuate nucleus of the hypothalamus and in nucleus tractus solitaries was examined. Triglycerides and leptin levels were increased in the high-fat diet mother. The number of neuropeptide Y positive cell bodies and neurons was significantly increased in the high-fat diet-F1 offspring (HDF-F1) as compared to Chow-F1. Leptin administration significantly decreased the food intake and increased the pSTAT3 expression levels in neurons in the arcuate nucleus of Chow-F1. However, leptin did not show any effect on food intake and had a reduced effect on pSTAT3 expression levels in neurons in the arcuate nucleus of HDF-F1. From the present domino effect, we conclude that mothers exposed to high-fat diet during pregnancy may pass the obese phenotype to the succeeding generation via altering hypothalamic leptin signaling.