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ZOU Zhihua

 

 

Professor, College of Life Sciences, Jilin University

email: zouzh@jlu.edu.cn

Tel: +86-0431-85155349

Fax: +86-0431-85155349

Life Science Building, Jilin University, 2699 Qianjin Street, Changchun, China

Postal Code: 130012

Research Interests

We study how various signals are integrated in gastrointestinal endocrine cells in order to dictate their functions and ultimately influence whole-body metabolism and energy intake.  In addition, we are also interested in the molecular mechanisms underlying cellular reprogramming, using adipocyte trans-differentiation as a model system.

 

Nutrient Sensing in the Gut

The detection of nutrients in the gastrointestinal (GI) tract is of fundamental significance to the control of energy intake, glycemia, and whole-body metabolism, yet little is known about even the basic aspects of this process. The presence of nutrients in the gut results in the secretion of regulatory peptide hormones (incretins, etc.), which act either locally in a paracrine fashion to activate afferent nerve terminals or adjacent cells, or in an endocrine fashion via intestinal capillaries and the lymphatic system to bind to specific receptors on cells in the pancreas, fat tissues, muscle and liver, etc. Entero-endocrine cells are able to 'taste' the luminal content and function as chemosensory transducers to link chemosignals in nutrients to the secretion of peptide hormones. The chemosensory mechanisms by which entero-endocrine cells detect nutritional chemosignals remain poorly understood. We focus on the roles of G-protein coupled receptors (GPCRs), transient receptor potential channels (TRP channels), and nuclear receptors in the control of entero-peptide hormone release.

 

White-brown adipocyte trans-differentiation

Mammals including humans have two major types of adipose tissue. White adipose tissue (WAT) accumulates and stores energy in the form of triacylglycerols and secretes adipokines and cytokines to influence food intake and whole-body metabolism, and it is well known that excess WAT may lead to insulin resistance and hyperlipidemia; on the other hand, brown adipose tissue (BAT), with its unusually high content of mitochondria and uncoupling protein-1 (UCP1), is specialized to dissipate energy as heat through UCP1 in a process called nonshivering thermogenesis, thus causing depletion of excess calories and protecting against obesity and diabetes. Besides these two types of classic adipose tissue, numerous studies have reported a "browning process", i.e., the appearance of brown-like adipocytes, called beige cells, in WAT depots in response to specific stimuli such as chronic cold exposure or beta-adrenergic stimulation. Basal levels of mitochondria and UCP1 in beige cells are low in comparison to classic brown adipocytes, but a robust program of mitochondrial biogenesis and respiration, as well as UCP1 expression, could be turned on by appropriate stimuli. Together, current evidence strongly supports that, stimulation of pre-existing brown adipocytes or induction of white adipocyte "browning" represents an attractive strategy to combat obesity and related complications. Some nuclear receptors including PPARs, thyroid receptor (TR), retinoic acid receptor (RAR), estrogen-related receptors (ERRs), and cellular enzymes including cyclooxygenase-2 (COX2) and deiodinase 2 (DIO2) are key cellular factors that promote adipocyte mitochondrial biogenesis and expression of UCP1. Agents that can stimulate the function of these cellular proteins have been shown to potently stimulate BAT activity and induce adipocyte browning, however, they all show some non-specific activities, which prevent their clinical use. Using computer-assisted design and virtual screening technology, combined with high-throughput quantitative RT-PCR detection of UCP1 induction, we are trying to identify agonists of above nuclear receptors and enzymes that can specifically stimulate "browning" without unwanted side effects. The results will provide valuable information for developing novel drugs for the treatment of obesity and related disorders, as well as new avenues to further understand molecular mechanisms underlying brown and beige adipocyte physiology.

Representative papers

1. Cummins SF, Erpenbeck D, Zou Z, Claudianos C, Moroz LL, Nagle GT, Degnan BM.  Candidate chemoreceptor subfamilies differentially expressed in the chemosensory organs of the mollusk Aplysia. BMC Biol 7:28, 2009

2. 吴仲南,邹志华,杜永均:果蝇嗅觉分子机理研究进展。昆虫学报,2009年07期

3.Boehm, U., Zou, Z., and Buck, L.  Feedback loops link odor and pheromone signaling with reproduction. Cell 123(4): 683-695, 2005

4. Ohta H., Tokimasa S., Zou Z., Funaki S., Kurahashi H., Takahashi Y., Kimura M., Matsuoka R., Horie M., Hara J., Shimada K., Takihara Y.  Structure and chromosomal localization of the RAE28/HPH1 gene, a human homologue of the polyhomeotic gene. DNA seq. 11(1-2), 61-73, 2000

5. Nomura, M., Zou, Z., Takihara, Y., Joh, T., Matsuda, Y., and Shimada, K. Genomic structures and characterization of the Rae1 family members encoding GPI-anchored cell surface proteins in embryonic mouse brain. J Biochem 120(5), 987-995, 1996

6. Zou, Z., Nomura, M., Takihara, Y., Yasunaga, T., and Shimada, K. Isolation and characterization of retinoic acid-inducible cDNA clones in F9 cells: a novel cDNA family encodes cell surface proteins sharing partial homology with MHC class I molecules. J Biochem 119(2), 319-328, 1996

7. Nishiguchi, S., Sakuma, R., Nomura, M., Zou, Z., Jearanaisilavong, J., Joh, T., Yasunaga, T., and Shimada, K. A catalogue of genes in mouse embryonic carcinoma F9 cells identified with expression sequenced tags. J Biochem 119(4), 749-767, 1996

8. Nishiguchi, S., Joh, T., Horie, K., Zou, Z., Yasunaga, T., and Shimada, K. A survey of genes in undifferentiated mouse embryonic carcinoma F9 cells: characterization of low-abundance mRNAs.  J Biochem 116(1), 128-139, 1994

 

 

 

College of Life Sciences, Jilin University,Changchun,China,130012

Tel:+86-431-81969061  Email: smxyld@jlu.edu.cn