Highlights
- Fat-specific protein 27 (Fsp27), is a lipid droplet-associated protein that prevents lipid mobilization and promotes lipid storage in cells.
- Silencing FSP27 reduced levels //of visceral fat, increased insulin sensitivity in both adipose tissue and liver.
Fatty liver, marked by high triglyceride levels in the liver, is the most frequent cause of chronic liver disease and contributes to metabolic syndrome, the cluster of factors that raise the risk of heart disease, diabetes and other health conditions.
"Obesity and fatty liver disease are intimately connected and pose a severe public health burden, given their high and growing prevalence in both adults and children," Baldan said.
In search of better options to treat fatty liver, Baldan looked to one of the proteins that regulate the metabolic fate of lipid droplets.
"When I think of fatty liver disease, I think of fatty hepatocytes -- liver cells. Each cell has many lipid droplets, and those droplets contain triglycerides. The lipid droplets aren't skinny-dipping in the cells, though. They are coated by proteins. One such proteins is called 'fat-specific protein 27', or FSP27," Baldan said.
Fasting generates a physiological response in which the body turns to stored fat for energy, and as that fat is mobilized from the adipose tissue, it reaches the liver, causing triglycerides to accumulate there.
Baldan and his team studied two groups of mice with obesity, high blood sugar and fatty liver disease: one that consumed a high-fat diet (the dietary model) and another that was genetically modified to have this trait (the genetic model). Both groups of mice then were treated with or without antisense oligonucleotides to silence Fsp27.
Silencing FSP27 resulted in a robust decrease in visceral fat, increased insulin sensitivity in both adipose tissue and liver, and improved whole-body glycemic control in both models. However, despite the improved function of the liver the researchers did not see decreased triglyceride accumulation in the liver. Baldan and his team are currently exploring ways to potentiate the anti-FSP27 treatment to also reduce fatty liver.
Overall, the team found that reducing the levels and activity of FSP27 may be beneficial in treating those who are obese or overweight and insulin-resistant, and that the therapeutic silencing of FSP27 in the mice fed a high-fat diet reduces body fat without worsening fatty liver disease.
"This study suggests that turning FSP27 down has potential as a therapy for insulin-resistant obese or overweight patients," Baldan said.
Reference
- Angel Baldan et al., Therapeutic silencing of Fat Specific Protein 27 improves glycemic control in mouse models of obesity and insulin resistance, Journal of Lipid Research(2016), http://www.jlr.org/content/early/2016/11/24/jlr.M069799.
Source-Medindia