A study shows that obese mice is been treated with catestatin (CST), a peptide naturally occurring in the body, showed significant improvement in glucose and insulin tolerance and reduced body weight. Researchers identified CST's role in the recruitment and function of macrophages in the liver as well as regulation of obesity-induced liver inflammation and insulin resistance. The study published in Diabetes.
In a normal human body, the liver helps regulate blood sugar by stimulating the body to absorb glucose as glycogen (for future use as energy). When sugar levels increase in the blood, the pancreas secretes insulin to decrease glucose production from the liver to maintain balance.
"We have shown that an endogenous peptide, catestatin, can directly suppress glucose production from hepatocytes and can indirectly suppress lipid accumulation in liver as well as macrophage-mediated inflammation in obese mice," said Sushil K. Mahata. "The net results are improved glucose tolerance and insulin sensitivity.
Therefore, this peptide has immense potential for an anti-obesity reagent as well as a novel drug to treat type 2 diabetes." When the liver stops responding to insulin, blood glucose levels rise, causing insulin production to go into overtime. If the body cannot maintain this heightened insulin production, the excess glucose leads to diabetes and other health disorders.
The liver also controls lipid production and metabolism. But in obesity, accumulation of lipids can cause fatty liver, resulting in cellular damage to the organ. In response to this damage, immune cells residing in the liver are activated, especially macrophages, and additional immune cells are recruited from the circulating blood.
Macrophages are specialized immune cells that promote tissue inflammation by secreting inflammatory molecules, which can lead to insulin resistance and metabolic disease. Treating obese mice with CST inhibited the recruitment of monocyte-derived macrophages to the liver and decreased inflammation, suggesting CST is an anti-inflammatory peptide.
CST treatment also lowered blood sugar and insulin levels to normal, and reduced fatty liver. To confirm the importance of naturally occurring CST, the authors studied mice that lacked CST. These mice ate more and were heavier but lost weight when treated with CST. The researchers theorize that naturally occurring CST may help maintain body weight by suppressing hunger and enhancing glucose tolerance.
In conclusion, author shows the improved glucose and insulin sensitivity with CST treatment may be partly explained by the anti-inflammatory effects of catestatin on the liver. They have identified a novel pathway for suppression of liver glucose production.
It could be used to compensate for the loss of naturally occurring CST or to bolster its impact. But further studies are needed to uncover how CST suppresses liver inflammation to improve metabolism.