Targeting "energy crisis" in fat cells could combat effects of obesity
The interplay between obesity and its many complications, such as type 2 diabetes, is complex and can involve factors such as inflammation and insulin resistance. Better understanding these relationships can reveal new ways to prevent adverse health effects faced by overweight subjects, and a new study has identified a new target that is likened to an "energy crisis" in fat cells.
The onset of obesity can negatively impact the body in many ways, such as increased risk of type 2 diabetes, cardiovascular disease and many cancers, with the way the condition directly affects cells thought to play an important intermediary role. This new study carried out by scientists at Sweden's Karolinska Institute sought to better understand what drives inflammation in fat tissue in people with obesity, the mechanisms of which have remained largely unclear until now.
They started by analyzing fat tissue from clinical cohorts and discovered that the way the cells metabolize phosphocreatine and creatine had been altered, seemingly as a result of weight gain. In human cells and in live mice, the team then showed that this has the effect of leading the fat cells into an "energy crisis," and causes them to draw on glucose instead.
"We believe that the impaired metabolism of creatine in the fat cells leads to an 'energy crisis' that causes the body to compensate by increasing glucose utilization," said Dr. Salwan Maqdasy, one of the study's first authors. "This stimulates the genes that lead to chronic inflammation in the body with an increased risk of insulin resistance."
Though the driving forces behind fat tissue inflammation and dysfunction more broadly have remained unknown, scientists have previously focused their attention on the role immune cells might play, however, potential treatments haven't produced any promising results in these experiments. The authors of this new study believe such efforts may be better targeted at fat cells instead.
Tempering inflammation in fat cells and minimizing the risk of insulin resistance could prove a valuable intervention in the way we treat obesity. Insulin resistance refers to an impaired ability of the body's cells to respond to insulin, which means they aren't easily able to absorb glucose from the blood. It is therefore a major risk factor for type 2 diabetes, which affects around 30 million people in the US alone, and other promising research has focused on targeting insulin resistance as a preventative measure.
For its authors, the findings of the new study present "unexpected" new pathways to target the dysfunction of fat tissue, and they've got a few ideas about where to look next.
"To determine the causes behind the development of adipose tissue inflammation, the next step is to investigate how the regulation of the enzymes that control the creatine metabolism in the body leads to altered glucose utilization," said Simon Lecoutre, the second lead author of the study.
The research was published in the journal Nature Metabolism.
Source: Karolinska Institute