Prdm16-Mediated Browning is Involved in Resistance to Diet-Induced and Monosodium Glutamate-Induced Obesity

Jia Liang,1 Ying Jia,1 Haijing Yan,1 Qingyu Shen,1 Weihua Bian,2 Dongmei Zhao,3 Yong Xu,1 Yongjun Jin,4 Meizi Yang1 1Department of Pharmacology, Binzhou Medical University, Yantai, People’s Republic of China; 2Department of Cell Biology, Binzhou Medical University, Yantai, People’s Republic of China; 3Department of Anatomy, Binzhou Medical University, Yantai, People’s Republic of China; 4Department of Endocrinology, Binzhou Medical University, Yantai, People’s Republic of ChinaCorrespondence: Meizi Yang; Yongjun JinDepartment of Pharmacology, Binzhou Medical University, Yantai, 264003, People’s Republic of ChinaTel +86 535 691 9507Fax +86 535 691 3163Email meizyang@126.com; endojin@126.comPurpose: To investigate resistance to diet-induced obesity (DIO) and monosodium glutamate (MSG)-induced obesity as well as the underlying mechanisms.Methods: Newborn mice were used to construct DIO and MSG-induced obesity models. Obesity indices, such as body weight, body length, Lee index, body temperature, food intake, fat weight, and leptin level, were examined. Mice that did not exhibit obesity were defined as the obesity-resistant group. The morphological changes of white adipose tissue were observed by hematoxylin and eosin staining, and expression levels of PR domain containing 16 (Prdm16) and uncoupling protein-1 (Ucp-1) in white adipose tissue were measured by Western blot.Results: Obesity-resistant mice fed a high-fat diet showed resistance beginning at week 5 along with lower weights and lengths than those in the obesity group from weeks 5 to 12. MSG-induced obesity-resistant mice showed features consistent with resistance to obesity from week 1 along with higher body lengths relative to the obesity group; however, the weight difference was not significant until week 10, when body weights decreased significantly in obesity-resistant mice. The Lee index was lower in obesity-resistant mice than in the obesity group and the normal group, further suggesting obesity resistance. Additionally, obesity-resistant mice showed higher levels of leptin, whereas obese mice induced by a high-fat diet showed leptin resistance. Furthermore, Prdm16 and Ucp-1 levels were both downregulated in the obesity group and upregulated in obesity-resistant mice, showing that white fat browning was highest in obesity-resistant mice.Conclusion: The phenotypes of mice with DIO and MSG-induced obesity differed. Obesity resistance might be related to Prdm16 and Ucp-1-mediated white adipocyte browning.Keywords: obesity resistance, brown adipose tissue, Ucp-1, adipocyte browning