Research: Studies over recent years revealed that an enhancement of brown adipose tissue activity can correct hyperlipidemia and prevent diet induced obesity and its harmful metabolic consequences. It has widely been assumed that all classical brown adipocytes in brown fat were functionally similar. This application is based on a recent unpublished discovery by Dr. Wang that there are two new, distinct, populations of classical brown adipocytes co-existing in normal brown fat that display distinct transcriptional fingerprints and morphology. The hypothesis is that they are active highly thermogenic and the resting low thermogenic brown adipocytes. This project will explore the function, dynamic and regulation of this two brown adipocyte subpopulations during development and under environmental and physiology challenges such as cold exposure and high fat diet feeding. By figuring out the key regulatory pathways leading to the diversity between the two subpopulations of brown adipocytes, we can identify the potential pharmaceutical targets to induce inter-conversion of brown adipocytes from low thermogenic capability to high thermogenic capability. Meanwhile, the proposed research will also investigate when the two subpopulations diverse during maturation; as well as how high fat diet challenge impairs the inter-conversion of the two subpopulations. In summary, the proposed research will unmask the complex physiology of brown adipose tissue, which is essential to improve our ability to identify the potential most effective therapeutic approaches against obesity and type II diabetes. Career goals: Dr. Wang's ultimate career goal as a biological scientist is to have her own productive academic lab devoted to metabolism research focusing on the pathogenesis and treatment of obesity, type 2 diabetes and the related metabolic syndromes. To be able to establish her independent research program, her immediate career objectives in the reward period are to: 1) Learn new techniques and knowledge in the field of developmental and cell biology. 2) Acquire new knowledge and expertise in developmental and cell biology, a direction different from her current mentor. 3) Further practice the skills for writing and publishing manuscripts by publishing more research articles. 4) Expand her network of colleagues for potential well-suited job offers and future collaborations. 5) Establish an independent funding record for my future funding applications. Career development plan: During the award period, Wang will strengthen her effectiveness in the above key career objectives through constant interactions with her mentor Dr. Philipp Scherer and collaborators Drs. Sean Morrison, Ralph DeBerardinis and Rana Gupta. She will also complete several courses provided by UTSW to prepare her for the independence.

Public Health Relevance

Enhancing brown adipose tissue energy burning activity can correct hyperlipidemia, insulin resistance and prevent diet induced obesity. This project will explore the function, dynamic and regulation of two brown adipocyte subpopulations, the 'active' highly thermogenic and the 'resting' low thermogenic brown adipocytes, during development and under environmental and physiology challenges such as cold exposure and high fat diet feeding. The proposed research will unmask the complex physiology of brown fat, which may improve our ability to develop strategies and novel targets to enhance thermogenesis in BAT for the treatment of obesity and type II diabetes without necessarily imposing life style and environmental changes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01DK107788-01
Application #
9014023
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2015-09-15
Project End
2018-07-31
Budget Start
2015-09-15
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
$111,963
Indirect Cost
$8,294
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Tao, Caroline; Holland, William L; Wang, Qiong A et al. (2017) Short-Term Versus Long-Term Effects of Adipocyte Toll-Like Receptor 4 Activation on Insulin Resistance in Male Mice. Endocrinology 158:1260-1270
Wang, Qiong A; Scherer, Philipp E (2016) Human Beige Adipocytes: Epiphenomenon or Drivers of Metabolic Improvements? Trends Endocrinol Metab 27:244-6
Shao, Mengle; Ishibashi, Jeff; Kusminski, Christine M et al. (2016) Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program. Cell Metab 23:1167-1184