In 1954 Vague identified central adiposity as a key determinant of several common chronic diseases including diabetes, myocardial infarction, hypertension and stroke. Vague contrasted the 'apple' pattern with metabolically beneficial gluteal - femoral adipose tissue (pears). This observation spawned more than a half century of clinical and laboratory investigation yet, there is still a major gap in our knowledge regarding th molecular underpinnings of adipose tissue patterning. It is clear that the relationship between adiposity and cardiovascular and diabetes disease risk is tightly related to fat patterning (apple vs. pear). In this regard, obese women who have a preponderance of abdominal subcutaneous fat (apple-shaped) have a higher risk of developing insulin resistance, diabetes and CVD relative to women who carry their excess weight in gluteal/thigh adipose tissue (pear-shaped). This proposal addresses the fundamental mechanisms associated with depot specific adipose function directly in humans. Our preliminary published and new unpublished studies support the hypothesis that fat depot specific gene expression and associated epigenetic signatures are maintained when abdominal vs. gluteal pre-adipocytes are cultured in vitro. The proposed new experiments will extend these studies to reveal genome-wide differences in epigenetic marks in adipose tissue and adipocytes from both men and women. We will also investigate the different gene expression patterns and associated epigenetic marks that define the pear vs. apple body type of the American adult female. We will uncover new fundamental molecular signatures and processes that are relevant to development of insulin resistance, diabetes and cardiovascular disease.

Public Health Relevance

Our preliminary published and new unpublished studies support the hypothesis that fat depot specific gene expression and associated epigenetic signatures are maintained when abdominal vs. gluteal pre-adipocytes are cultured in vitro. The proposed new experiments will extend these studies to reveal genome-wide differences in epigenetic marks in adipose tissue and adipocytes. We hypothesize that these epigenetic marks are important to understanding several common chronic diseases such as diabetes and cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK107009-04
Application #
9723084
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Blondel, Olivier
Project Start
2016-06-28
Project End
2021-05-31
Budget Start
2019-06-01
Budget End
2021-05-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Adventhealth Orlando
Department
Type
DUNS #
824843312
City
Orlando
State
FL
Country
United States
Zip Code
32803
Hsu, Ya-Ling; Hung, Jen-Yu; Chang, Wei-An et al. (2018) Hypoxic Lung-Cancer-Derived Extracellular Vesicle MicroRNA-103a Increases the Oncogenic Effects of Macrophages by Targeting PTEN. Mol Ther 26:568-581
Chang, Wei-An; Tsai, Ming-Ju; Jian, Shu-Fang et al. (2018) Systematic analysis of transcriptomic profiles of COPD airway epithelium using next-generation sequencing and bioinformatics. Int J Chron Obstruct Pulmon Dis 13:2387-2398
Divoux, Adeline; Sandor, Katalin; Bojcsuk, Dora et al. (2018) Differential open chromatin profile and transcriptomic signature define depot-specific human subcutaneous preadipocytes: primary outcomes. Clin Epigenetics 10:148
Chen, Yi-Jen; Chang, Wei-An; Wu, Ling-Yu et al. (2018) Systematic Analysis of Differential Expression Profile in Rheumatoid Arthritis Chondrocytes Using Next-Generation Sequencing and Bioinformatics Approaches. Int J Med Sci 15:1129-1142
Chen, Szu-Chia; Chen, Feng-Wei; Hsu, Ya-Ling et al. (2017) Systematic Analysis of Transcriptomic Profile of Renal Cell Carcinoma under Long-Term Hypoxia Using Next-Generation Sequencing and Bioinformatics. Int J Mol Sci 18:
Chen, Yi-Jen; Chang, Wei-An; Hsu, Ya-Ling et al. (2017) Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches. Int J Mol Sci 18:
Divoux, Adeline; Xie, Hui; Li, Jian-Liang et al. (2017) MicroRNA-196 Regulates HOX Gene Expression in Human Gluteal Adipose Tissue. Obesity (Silver Spring) 25:1375-1383
Chen, Yi-Jen; Chang, Wei-An; Huang, Ming-Shyan et al. (2017) Identification of novel genes in aging osteoblasts using next-generation sequencing and bioinformatics. Oncotarget 8:113598-113613