Thursday, February 8, 2018

Animal studies show that naturally occurring peptide catestatin has potential as anti-obesity and type 2 diabetes treatment

Research by team from University of California San Diego School of Medicine shows that treating obese mice with catestatin (CST), a peptide naturally occurring in the body, showed significant improvement in glucose and insulin tolerance and reduced body weight.

In a study published in journal Diabetes, researchers identified catestatins's role in the recruitment and function of macrophages in the liver as well as regulation of obesity-induced liver inflammation and insulin resistance.

"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, PhD, professor of medicine at UC San Diego School of Medicine. "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."

Treating obese mice with catestatin inhibited the recruitment of monocyte-derived macrophages to the liver and decreased inflammation, suggesting catestatin is an anti-inflammatory peptide. Catestatin treatment also lowered blood sugar and insulin levels to normal, and reduced fatty liver. Administering catestatin had no effect on insulin or glucose tolerance in control lean mice, showing that the effect of catestatin is restricted to obese animals. This difference may be explained by the reduced levels of normal catestatin in obese mice compared to the lean control animals. To confirm the importance of naturally occurring catestatin, the authors studied mice that lacked catestatin. These mice ate more and were heavier but lost weight when treated with catestatin. The researchers theorize that naturally occurring catestatin may help maintain body weight by suppressing hunger and enhancing glucose tolerance.

"The improved glucose and insulin sensitivity with catestatin treatment may be partly explained by the anti-inflammatory effects of catestatin on the liver," said Mahata. "We have identified a novel pathway for suppression of liver glucose production that could be used to compensate for the loss of naturally occurring catestatin or to bolster its impact. But further studies are needed to uncover how catestatin suppresses liver inflammation to improve metabolism."

Citation: Ying, Wei, Sumana Mahata, Gautam K. Bandyopadhyay, Zhenqi Zhou, Joshua Wollam, Jessica Vu, Rafael Mayoral, Nai-Wen Chi, Nicholas J.g. Webster, Angelo Corti, and Sushil K. Mahata. "Catestatin Inhibits Obesity-Induced Macrophage Infiltration and Inflammation in the Liver and Suppresses Hepatic Glucose Production Leading to Improved Insulin Sensitivity." Diabetes, 2018. doi: 10.2337/db17-0788.

Funding:  Department of Veterans Affairs, American Heart Association, National Natural Science Foundation of China, Noland Scholarship.

Adapted from press release by University of California San Diego School of Medicine.

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