Membranes, actin and morphogenesis
WAT and BAT
Energy homeostasis is crucial since excess fat storage leads to obesity and negatively impacts the body’s metabolic health with associated predisposition to diseases including diabetes. There are two distinct types of adipose tissue:
1) White adipose tissue (WAT), when in excess, is considered to negatively impact on health due to its role in triglyceride storage and associated obesity.
2) Brown adipose tissue (BAT), in contrast, is considered to be favourable to health. Exposure to the cold rapidly activates signalling pathways in BAT which modulate gene expression and promote the capacity for thermogenesis and consumption of fat stores. Remarkably, WAT depots can also respond to a long term cold stimulus by specific genetic and morphological changes that result in a more BAT-like appearance. We are investigating the factors and signalling pathways that control the function of brown adipocytes.
CIDEA and Lipid Droplets
The study of factors that regulate lipid storage in different tissues is essential for understanding and controlling metabolic disorders. Cellular lipid storage is determined by a group of proteins that coat lipid droplets and facilitate storage or utilisation by regulation of metabolic processes. The brown fat protein CIDEA has important roles in lipid droplet formation and function. We have defined the molecular mechanism of CIDEA-dependent lipid droplet enlargement through binding of phosphatidic acid. By studying the function and regulation of CIDEA, we are determining the impact of this protein on lipid storage in different metabolic tissues, the importance of controlling the expression of metabolic regulatory systems in response to environmental stimuli, and the impact of tissue-specific gene expression on cellular bioenergetics.
MicroRNA Signalling in brown and white adipocytes
MicroRNAs are small non coding RNAs that are important regulators of gene expression and essential for cell differentiation. They can be secreted through incorporation into vesicles and their presence in several body fluids suggests involvement in cell to cell communication. We are investigating the roles that microRNAs play in determining the key differences between brown and white adipocytes and the mechanism of their secretion and systemic effects on other tissues.
- Barneda D, Planas-Iglesias J, Gaspar ML, Mohammadyani D, Prasannan S, Dormann D, Han GS, Jesch SA, Carman GM, Kagan V, Parker MG, Ktistakis NT, Dixon AM, Klein-Seetharaman J, Henry S, Christian M. The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix. Elife. 2015. doi: 10.7554/eLife.07485. PMID: 26609809
- Nikolopoulou E, Papacleovoulou G, Jean-Alphonse F, Grimaldi G, Parker MG, Hanyaloglu AC, and Christian M. Arachidonic acid-dependent gene regulation during preadipocyte differentiation controls adipocyte potential. J. Lipid Res. 2014 55(12):2479-2490. PMID: 25325755.
- Rosell M, Kaforou M, Frontini A, Okolo A, Chan YW, Nikolopoulou E, Millership S, Fenech ME, MacIntyre D, Turner JO, Moore JD, Blackburn E, Gullick WJ, Cinti S, Montana G, Parker MG, Christian M. Brown and white adipose tissues. Intrinsic differences in gene expression and response to cold exposure in mice. Am J Physiol Endocrinol Metab. 2014. 306(8):E945-964. PMID: 24549398.
- Kiskinis E, Chatzeli L, Curry E, Kaforou M, Frontini A, Cinti S, Montana G, Parker MG, Christian M. RIP140 represses the “brown-in-white” adipocyte program including a futile cycle of triacyclglyerol breakdown and synthesis. Mol Endocrinol. 2014. 28(3):344-356. PMID: 24479876.