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Research Summary

Adipose tissue plays a central role in the development of insulin resistance and diabetes. Increasing fatty acid storage and utilization in adipose tissues in order to limit ectopic lipid accumulation into non adipose tissues, is essential to restore insulin sensitivity and treat type 2 diabetes. Mammals have two major types of adipose tissues, white and brown. White fat is essential for fatty acid storage, while brown fat is an essential component of non-shivering thermogenesis, and has the ability to utilize fatty acid and generate heat due to the unique presence of the protein UCP1. Under certain circumstances such as chronic cold exposure, white adipocytes can be converted into brown-like fat cells or beige cells with high oxidative and energy wasting capacity, a process called browning of white fat.

In humans, brown fat is inversely correlated with body mass index, and its activation is associated with metabolic improvements. In animal models, brown adipose tissue deficiency is associated with obesity and diabetes while increasing brown fat or browning of white fat has protective effects. Thus, activating brown fat or inducing browning of white adipose tissue has attractive potential for the treatment of obesity and diabetes.

Our lab investigates the molecular pathways that control the development, differentiation and function of white and beige/brown adipose cells. The ligand-gated transcription factor PPARg has been shown to play a major role in these processes. We have identified novel PPARg modulator small molecules that can convert human white adipocytes into UCP1-expressing brown-like adipocytes. Our lab aims at identifying the molecular mechanisms responsible for the white-to-brown adipocyte phenotypic switch, as well as identifying novel factors essential for brown adipocyte development and function. We are also investigating the roles that Bone Morphogenetic Proteins (BMPs) and the transcription factors PPARa play in those processes.

Senescence (aging of cells) is another area of research focus. Senescence of adipose tissue cells is closely associated with common cardiometabolic complications including type 2 diabetes and cardio-vascular disease. We are investigating the key drivers of senescence in the different adipose tissue cells (endothelial cells, mesenchymal stem cells, adipocytes) in metabolic diseases, how senescent cells communicate with other cells and tissues to impact metabolism, and how to inhibit senescence in adipose tissue.



Page Manager: Mattias Lindgren|Last update: 1/31/2019

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