According to the World Health Organization (WHO), overweight and obesity are global problems whose rates are continually increasing. In 2014, more than 1.9 billion adults (18 years and older) were overweight. Of these, 600 million were obese. Obesity and overweight are major issues in the United States as well. The CDC reports that more than one-third or 36.5% adults in this country are obese. Factors that lead to overweight or obesity are numerous starting with a sedentary lifestyle and unhealthy diet. The latest study made a groundbreaking discovery regarding the mechanism that leads to fat formation and obesity.
Fat Formation Mechanism
Obesity is primarily influenced by excessive calorie intake which results in expansion of adipose tissue by hypertrophy and hyperplasia. The later results from the differentiation of adipocyte precursor cells (APCs) that reside in adipose depots. Dr. Brian Feldman and a team of researchers at the Stanford University School of Medicine carried out the study to identify genes that change activity in response to glucocorticoid medications, which are associated with side effects such as obesity and Type 2 diabetes. However, they discovered more than they expected after their study also led to the revelation of the underlying mechanisms which could lead to the fat formation and obesity. They used fat cells and fat stem cells in a laboratory, followed by human and mice studies.
Analysis of this process has elucidated a network of mainly transcription factors that drive APCs through the process of differentiation. Researchers used in vitro and in vivo approaches in a bid to reveal a signaling pathway that inhibits the initiation of the adipocyte differentiation program. They found that stored mature fat cells secrete the hormone ADAMTS1 which toggles a “switch” that regulates whether the surrounding stem cells differentiate into more fat cells which are also ready to store fat.
Findings, published in the journal Science Signaling, indicate that the production of ADAMTS1 hormone elevates fat formation as a consequence of intake of glucocorticoid medications and high-fat diet. Dr. Feldman explains, while people are aware that eating more leads to weight gain, the study goes a long way to provide a detailed insight into the process. Although it was perfectly clear that food ingestion was associated with the signal that tells the organism to store fat, the factor that gates or triggers the process in vivo was unknown.
High-Fat Diet and ADAMTS1 Hormone
Mouse adipocytes secreted the extracellular protease ADAMTS1, which triggered the production of the cytokine pleiotrophin (PTN) and promoted proliferation rather than differentiation of APCs. To simplify, mice that were given glucocorticoids had a reduction of the ADAMTS1 hormone. On the other hand, when mice were genetically engineered to produce higher amounts of this hormone, they had fewer mature fat cells and smaller fat depots.
When purified ADAMTS1 hormone was added to fat stem cells, the hormone blocked the glucocorticoid-induced inflammation from fat stem cells to mature fat cells, which means the hormone acts as a signal outside of fat cells. Mice were fed a high-fat diet which made them fatter. New fat cells matured in visceral fat tissue with reduced levels of this hormone. That said, higher aDAMTS1 levels and less fat cell maturation were spotted in subcutaneous fat tissue.
Based on these findings, it is safe to conclude that this particular hormone is an important regulator of the difference in mature fat cells between two types of fat. It’s also crucial to bear in mind that same results were found in humans, as well.
The research also showed that stress hormones transmit a message via ADAMTS1 to mature more fat cells, thus explaining why stress is also linked to obesity.
Stanford University scientists made a groundbreaking discovery after they identified the mechanism that leads to fat formation. This important research explains how high-fat diets, stress, and even some medications lead to obesity. Scientists hope their findings will lead to new treatments that could prevent obesity or help overweight/obese individuals to lose weight.