University of Tennessee at Knoxville, 2000
Regulation of energy Homeostasis
- Brown adipocyte biology
- Central regulation of energy homeostasis
- Macrophage inflammation, insulin resistance and athersclerosis
My research focuses on the molecular basis of energy homeostasis, including both central and peripheral regulation of energy balance, insulin sensitivity, lipid and cholesterol metabolism, and brown and white adipocyte biology, by using transgenic/knockout models, molecular biology techniques and physiological approaches.
One of my research interests is to understand the mechanisms mediating the induction of brown adipocytes in white fat depot. Unlike white fat, which serves as energy storage depot, the function of brown fat is to maintain body temperature during cold stress by generating heat through the uncoupling of oxidative phosphorylation via the uncoupling protein 1 (UCP1). Cold exposure or adrenergic stimulation induces the appearance of brown adipocytes in traditional white fat depots in rodents and other small animals, as demonstrated by their multilocular morphology, abundant mitochondria and the expression of the brown fat-specific UCP1. This inducible brown adipocyte phenotype is significant since it reverses both diet-induced and genetic obesity. Importantly, recent data demonstrate that metabolically active brown adipose tissue also exists in adult humans. Therefore, inducing brown adipocytes in white fat may represent a novel approach in the prevention and treatment of obesity. Currently, we are studying the mechanisms by which brown adipocytes can be induced in white fat depots using cellular and molecular biology techniques, whole genome profiling approaches and genetically engineered mouse models.
Another part of my research is to understand how energy homeostasis is regulated through hypothalamic neuronal network. Obesity results from imbalance between energy intake and energy expenditure. Hypothalamus is the center in the regulation of energy homeostasis. The different neurons in the hypothalamus receive and integrate signals from the periphery and send signals to higher brain centers, which corporately regulate food intake and energy expenditure, thereby maintaining energy homeostasis. We are currently interested in how hypothalamic neuronal network adapts and being re-programmed in obesity, which may be an underlying mechanism in the development of the metabolic syndrome.
Last but not least, I am studying the role of macrophage AMPK in the protection against insulin resistance and atherosclerosis. Macrophage inflammation plays a key role in the development of metabolic disorders including insulin resistance and atherosclerosis. Inflammatory responses in obesity can be activated by altered nutrient metabolism (e.g. excess lipids and modified lipoprotein particles). High levels of cholesterol and saturated fatty acids (SFAs) alter macrophage function and result in macrophage abnormalities by inducing macrophage endoplasmic reticulum (ER) stress. ER stress has been linked to a wide range of complex diseases, including obesity, diabetes and atherosclerosis.
AMP-activated protein kinase (AMPK) is an evolutionally conserved cellular energy sensor that regulates metabolic pathways in lipid, cholesterol and glucose metabolism. We have previously reported that macrophage AMPK protects against lipid-induced inflammation and insulin resistance in vitro. Therefore, we are currently studying whether macrophage AMPK protects against obesity-associated insulin resistance and atherosclerosis in animal models and whether this is mediated through AMPK’s regulation of macrophage lipid and cholesterol homeostasis, which leads to the protection against lipid- and cholesterol-induced ER stress.
First Name Surname Position Emily Bruggeman PhD Student firstname.lastname@example.org Qiang Cao Post-doc email@example.com Xin (Cindy) Cui Post-doc firstname.lastname@example.org Shuping Kou Masters email@example.com Fenfen Li PhD Student firstname.lastname@example.org