Adipocytes do more than simply store fat. They also play a role in metabolic diseases. Through better understanding of how adipose cells function and interact, researchers can develop new, targeted therapies for treating adipositas and diabetes.


Adipose tissue: a multitasker organ
Acting as an energy bank, storing and releasing energy is just one role of the highly dynamic adipose tissue. Adipocytes, mature fat cells, also produce and secrete hormones, which influence energy intake. Moreover, some adipocytes can convert chemical energy in heat. Adipocytes are not the only components of adipose tissue, which is also made of connective tissue and other cells such as preadipocytes, macrophages, fibroblasts, endothelial cells and stem cells. These cells work together to maintain adipocyte integrity and hormonal balance.

Trying to identify the link between adipositas and insulin resistance
“Adipose tissue contains many molecules that are involved in processes necessary for maintaining metabolic balance. This is why it plays a crucial role in the onset of metabolic diseases,” explains Melissa Olekson, scientific support specialist at PromoCell. Today obesity presents a global health epidemic. It is linked to high-mortality diseases such as type 2 diabetes mellitus and cardiovascular pathologies. Every year, obesity becomes more widespread. Recent studies suggest that 18% of men and 21% of women globally will be classified as obese by 2025, with more than 300 million people suffering from obesity-associated type 2 diabetes (Noncommunicable Disease Risk Factor Collaboration, 2016). Based on this alarming forecast, researchers are striving to better characterize the molecular mechanisms that link adipose tissue with metabolic disorders. Obesity results when energy intake surpasses energy expenditure and also depends on the interaction of many factors including genetics, epigenetics, environment and lifestyle (Schwartz et al., 2017). This explains why, unlike most endocrine diseases, researchers still struggle to understand the underlying disease mechanisms. Despite decades of research and considerable investment, effective therapies are still lacking.
Brown and beige adipocytes: potential targets for therapy
Along with interventions targeted at improving adipose tissue health, brown adipose tissue and beige adipocytes show promise as therapeutic targets for adipositas. In fact, brown adipose tissue is central to energy homeostasis and to glucose homeostasis. Beige adipocytes reside among white adipocytes and can be activated in response to external stimuli such as cold temperatures, exercise and nutrition. During this “browning” process, beige adipocytes acquire brown adipose tissue characteristics, consuming energy by heat production. Alternatively, these stimuli could also induce transdifferentiation of white adipocytes into mature brown adipocytes. Hormones including prostaglandins, natriuretic peptide, BMP or VEGF regulate brown and beige adipocytes. These factors can increase energy expenditure and improve glucose homeostasis and insulin sensitivity. Emerging data support the creation of a “metabolic sink” for glucose and triglycerides, which would treat obesity by promoting the development of beige adipocytes (Sidossis and Kajimura, 2015). An alternative therapeutic approach could base on blocking regulators such as TGF-β, which hamper the function of brown and beige adipocytes in obese patients. In some studies, TGF-β neutralizing antibodies protect animals from obesity and insulin resistance (Yadav et al, 2011).Preadipocytes: peeking into the development of metabolic diseases

Melissa Olekson is a scientific support specialist, helping researchers to establish in vitro adipose-cell models for looking into molecular processes in metabolic diseases.
To characterize molecular pathways of metabolic diseases and identify new treatment modalities, relevant in vitro models are needed. “Preadipocytes offer a very useful cell model. They not only provide insights in key human signaling pathways, but also offer a platform to test possible treatments in vitro,” explains Olekson. Scientists can use preadipocytes to investigate physiological and pathological mechanisms controlling the function and differentiation of adipose tissue. “The techniques used in these studies include modification of gene expression and analysis of cell markers,” says Olekson. “Preadipocytes can also be used as a cell model for diabetes studies or for observing adipogenic differentiation of mesenchymal stem cells.” For example, researchers can compare preadipocytes from diabetic patients with preadipocytes from healthy donors to detect differences in intracellular processes, gene expression and cytokine release.
By investigating interactions between healthy and immune cells, scientists gain insights in the chronic inflammatory processes underlying adipositas-associated type 2 diabetes. In a recent study, Kongsuphol and colleagues co-cultured adipose tissue with immune cells in a microfluidic-based in vitro model. As this allows the measurement of cytokines and provides data on inflammatory reactions and insulin sensitivity, this model could be used for screening diabetic drugs.
Similar to these researchers, scientists around the globe are striving to understand the complexity of our “rechargeable batteries.” In their search for new methods to fight obesity, they seek insights in the extreme plasticity of adipose tissue.
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Preadipocytes: live cell imaging
This YouTube video from Nanolive shows label-free live cell imaging of a preadipocyte with their 3D Cell Explorer.