Low temperature exposure induces the formation of adipocytes in vitro

A research paper, published in the journal Scientific Reports, reports an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC), which relies on differentiation at 32 °C instead of 37 °C. Results indicate that BM-MSC can be driven to forming beige-like adipocytes in vitro by exposure to a reduced temperature.

This study shows for the first time that the way in which fat is made within the body is not 'pre-programmed' during the early years of development as previously thought but even in adulthood cells can be influenced by our environment to change the type of fat that is formed. The work could help us to better understand and tackle issues related to obesity and metabolism and develop new ways of controlling diseases such as diabetes.

Key points of this article are as follows.
a. Mouse Mesenchymal stem cells (mMSCs) achieve an adipogenic phenotype and express both UCP1 and leptin
b. Enhanced adipogenesis and morphological changes show signs of browning in hypothermic conditions
c. Temperature-related changes in differentiated mMSC-derived adipocytes: increased UCP1 protein expression and leptin translocation to the nucleus
d. Lower temperature conditions affect PGC-1α expression, the bioenergetic status and reduce coupling efficiency of MSC-derived adipocytes
e. Mouse MSC-derived adipocytes exhibit characteristics of white, beige and brown adipocytes at protein and mRNA level

The two-year study was led by Dr Virginie Sottile, Associate Professor in Stem Cell Biology & Cell Differentiation, and Professor Michael Symonds in the University's School of Medicine.

It focused on how the body decides whether to form 'good' brown adipose tissue (BAT) or white adipose tissue, the 'bad' type of fat. BAT could heat by burning fat, sugar and excess calories and helps to regulate blood sugar, while
white adipose tissue stores energy and accumulates, causing weight gain over time.

Most commonly, brown fat is found in babies and hibernating animals as nature's way of keeping them warm while at their most vulnerable. However, in recent years scientists have discovered that a small amount of brown fat is found in adults, and that the body retains the ability to form more under certain conditions.

"As we all know, exposure to lower temperatures can promote the formation of brown fat but the mechanism of this has not yet been discovered. The trigger was believed to be the body's nervous system and changes in the way we eat when we are cold. " said Dr Sottile.

In the study, even by making modest changes in temperature, stem cells can be activated to form brown fat at a cellular level. The cells are not pre-programmed to form bad fat and stem cells can respond if we apply the right change in lifestyle.

The study developed a new in vitro system made from bone marrow stem cells, which gave us an advantage over previous rodent models as we could study more accurately how specifically human cells would be affected by a decrease in temperature.

In the future, it could be used as a testing ground to rapidly screen potential treatments by looking at how specific molecules interact with the cells. We could even use patients' own cells to develop a tailored approach to finding out how we can more effectively treat them for diseases such as diabetes.

But people who are keen to make a positive impact on their weight by reducing their white fat stores and increasing their percentage of calorie-burning brown fat may not even have to brave lower temperatures to achieve this.

Dr Sottile said that "The next step in our research is to find the actual switch in the cell that makes it respond to the change of temperature in its environment," "That way, we may be able to identify drugs or molecules that people could swallow that may artificially activate the same gene and trick the body into producing more of this good fat."

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