Cilia and Metabolic Disorders
Obesity and the associated type 2 diabetes mellitus represent a major public health issue. It is accepted that the development of obesity stems from the interaction of environmental factors with genetic factors. Although monogenic genetic obesities are rare, the elucidation of the physiological function of causal genes, such as the identification of leptin in ob/ob mutant mice, was transformative in understanding obesity physiopathology. Cilia-related disorders (ciliopathies) are a significant part of genetic obesities, such as Bardet-Biedel syndrome and Alstrom syndrome, highlighting the important role of ciliary signaling in the pathogenesis of obesity.
Primary cilia present on most cell surfaces in the human body and are like cellular "antennas" used by cells to sense the environment ranging from mechanical and chemical cues to temperature or osmolarity. Cilia dysfunctions contribute to a wide spectrum of human syndromic diseases. However, major gaps exist in understanding the molecular mechanism behind cilia dysfunction-associated manifestations.
Based on initial discoveries made in unique ciliopathy rodent models, Dr. Hu is collaborating with a highly complementary team to investigate the unexpected but central role primary cilia play in adipogenesis of both white and brown fat tissues, and the implications for human metabolic disorders.