Dr. Shapiro: Aaron, thank you for meeting with me today to discuss the development of human white (WAT) and brown (BAT) adipose tissue models for studying metabolic diseases. To start out, can you tell me a bit about WAT and BAT and their functional and physiological roles in humans?
Dr. Cypess: Human adipose tissue is polychromatic and found throughout the body with functional diversity. Brown adipocytes, which make up brown adipose tissue (BAT), can be found in certain regions of the body in the cervical, supraclavicular, and axillary regions; along the spine in the paravertebral region; and distinct locations within the abdomen. BAT plays an important role in adaptive thermogenesis during periods of cold stress; in humans, this tissue is particularly abundant in infants. White adipocytes, which make up the white adipose tissue (WAT), are found in subcutaneous depots under the skin or in visceral depots in the epicardial, omental, mesenteric, perirenal, and gonadal regions. These two types of WAT differ in their metabolic impact; subcutaneous WAT is supposed to be metabolically neutral or possibly even beneficial, while the visceral WAT is what is associated with cardiometabolic disease.
It is important to remember that adipose tissues, like every tissue of in the body, are made up of a diversity of cell types. For example, human WATs show many cell types—besides adipocytes, there are stem cells, several types of immune cells, endothelial cells, and others, each with distinct marker genes. Each of these cell types can act locally but can also impact organs throughout the body, and the roles of adipose tissues are only beginning to be discovered. This is something that I as an endocrinologist am particularly interested in.
Dr. Shapiro: What types of cell models are typically used to study the transcriptional, functional, and metabolic regulation and dysregulation of white and brown adipocytes?
Dr. Cypess: Human adipose tissue is a complex organ with numerous functional and endocrine roles. To understand the physiology and disfunction of this tissue, models such as primary cells, human induced pluripotent stem cells, adipose-derived stem cells originating from the stromal vascular fraction, and Simpson-Golabi-Behmel syndrome cells have been used. A common issue with these cell lines, however, is the limited information regarding functional, structural, and genetic characteristics as well as possible inconsistencies after numerous population doublings. Because of these limitations, we worked in collaboration with ATCC to generate immortalized clonal human brown and white preadipocytes cell lines that can be used as standardized in vitro models.
Dr. Shapiro: Can you tell me a bit about the development of these new immortalized preadipocyte models?
Dr. Cypess: In our collaborative study with ATCC, our team—led by Dr. Cheryl Cero and me—generated the immortalized, clonal human white (ATCC CRL-4063) and brown (ATCC CRL-4062) preadipocyte models from the abdominal subcutaneous and perirenal depots, respectively, of a male patient. These cells were immortalized with hTERT and were extensively characterized via genotypic, phenotypic, and functional testing. Through these analyses, we confirmed that the differentiated white and brown immortalized adipocytes phenocopied primary adipocytes in terms of adrenergic signaling, lipolysis, and thermogenesis. Further, our transcriptomics analysis via RNA-seq were consistent with our functional studies and established a molecular signature for each cell type.
These models were developed following the FDA requirements of reported manufacturing processes, testing methodology, and technical characteristics. You can see our data and in-depth description of these cell models in our recent publication in the journal Endocrinology entitled “Standardized In Vitro Models of Human Adipose Tissue Reveal Metabolic Flexibility in Brown Adipocyte Thermogenesis.”
Did you know?
These novel brown and white preadipocyte models provide powerful tools for understanding brown and white fat physiology and for developing new diagnostics and treatments for metabolic diseases. If you are interested in learning more about these models, please read the recent publication or watch our on-demand webinar.
Meet the scientists
Aaron M. Cypess, MD, PhD, MMSc
Senior Investigator and Chief, Translational Physiology Section, DEOB, NIDDK, NIH
Dr. Aaron Cypess is a senior investigator at the National Institutes of Health, where his research group uses a combination of clinical trials and basic science to help understand how brown fat works at the levels of the cells and then to translate the information into practical ways to treat people with obesity, diabetes, and other chronic illnesses. Previously, Dr. Cypess was an assistant professor at Harvard Medical School, where he investigated the pathogenesis of metabolic diseases. He received his MD from the Joan & Sanford I. Weill Medical College of Cornell University and his MMSc from Harvard Medical School. Dr. Cypess earned his PhD from Rockefeller University where he studied Signal Transduction by the Glucagon Receptor.
Brian Shapiro, PhD
Marketing Segment Manager, Oncology, ATCC
Brian A Shapiro, PhD, works to communicate the scientific breakthroughs of ATCC’s product development laboratories to the biomedical research community. Brian is the Executive Producer of ATCC's Podcast, Behind the Biology. Previously, he worked at Virginia Commonwealth University, where he investigated the role of pre-mRNA splicing in the multi-drug resistance of lung cancer. Dr. Shapiro attended the Medical College of Georgia, where his research focused on adrenal physiology as well as diseases of the epidermis.
