Research
The primary aim of the Nielsen Lab is to investigate the acute metabolic functions of long, non-coding RNA in human brown and white adipose tissue. While the human genome consists of ~98% non-protein coding sequences, previously considered to be ‘junk DNA’ without biological relevance, it is currently understood that around 80% of the non-protein coding regions indeed do have a function. The importance of these non-protein coding regions is supported by the finding that organismal complexity correlates with the non-protein coding proportion of the genome, rather than the number of protein-coding genes.
One class of non-coding RNA is long, non-coding RNA (lncRNA), which are RNA transcripts of >200 nucleotides length. LncRNAs are regulatory RNAs commonly described as recruitment molecules at the DNA level, however, LncRNAs have diverse cellular roles not limited to the nucleus. In the Nielsen group, we are investigating the acute metabolic functions of these lncRNA in both human white and brown adipocytes and whether these can act acute modulators of metabolism.
To study lncRNA functions, we use preadipocytes isolated from fat biopsies from various fat depots of adult humans, including the supraclavicular brown fat and subcutaneous abdominal white fat depots.
Brown adipose tissue is of particular interest to us as it is not only stored in the same way as "normal" white adipose tissue, but is also capable of consuming lipids as energy by producing heat as a physiological reaction to cold. Several studies have shown a brown fat-like white fat phenotype in mice that is induced through a process called "browning." Certain disease states imply that "white fat" browning can also occur in humans and "browning" of white fat deposits in obese people can counteract obesity and type 2 diabetes.
In addition to brown fat, we isolate muscle stem cells (satellite cells) from skeletal muscle in humans and grow them in culture. The purpose is to investigate whether this early muscle cell stage is influenced by lifestyle-related factors such as physical inactivity, obesity and type 2 diabetes.
In our biobank we have cells from approximately 1.000 individuals including muscle stem cells and preadipocytes from various adipose tissue depots. These human primary cell cultures are isolated from exceptionally well-phenotyped individuals, thus representing a wide range of disease status, body mass, physical activity level, sex and age, giving us a unique opportunity to translate the results from our molecular studies back to the cell donors.
Conferences
CPHBAT
Brown and white adipose in metabolism, plasticity and metabolic cross talk. June 3-4, 2019, Copenhagen
NON-CODING RNAs IN METABOLIC DISEASE
May 6-8 2019, Copenhagen
CPHBAT
May 3-4 2017, Copenhagen