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Catestatin Inhibits Obesity-Induced Macrophage Infiltration and Inflammation in the Liver and Suppresses Hepatic Glucose Production Leading to Improved Insulin Sensitivity

Ying, Wei and Mahata, Sumana and Bandyopadhyay, Gautam K. and Zhou, Zhenqi and Wollam, Joshua and Vu, Jessica and Mayoral, Rafael and Chi, Nai-Wen and Webster, Nicholas J. G. and Corti, Angelo and Mahata, Sushil K. (2018) Catestatin Inhibits Obesity-Induced Macrophage Infiltration and Inflammation in the Liver and Suppresses Hepatic Glucose Production Leading to Improved Insulin Sensitivity. Diabetes, 67 (5). pp. 841-848. ISSN 0012-1797 . https://resolver.caltech.edu/CaltechAUTHORS:20180220-082141564

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Abstract

The activation of Kupffer cells (KCs) and monocyte (Mc)-derived recruited macrophages (McMΦs) in the liver contributes to obesity-induced insulin resistance and type 2 diabetes. Diet-induced obese (DIO) mice treated with Chromogranin A (CgA) peptide catestatin (CST) showed several positive results. These included decreased hepatic/plasma lipids and plasma insulin, diminished expression of gluconeogenic genes, attenuated expression of pro-inflammatory genes, increased expression of anti-inflammatory genes in McMΦs, and inhibition of the infiltration of McMΦs resulting in improvement of insulin sensitivity. Systemic CST knockout (CST-KO) mice on normal chow diet (NCD) ate more food, gained weight, and displayed elevated blood glucose and insulin levels. Supplementation of CST normalized glucose and insulin levels. To verify that the CST deficiency caused macrophages to be very pro-inflammatory in CST-KO-NCD mice and produced glucose intolerance, we tested the effects of FACS-sorted F4/80+Ly6C- cells (representing KCs) and F4/80-Ly6C+ cells (representing McMΦs) on hepatic glucose production (HGP). Both basal and glucagon-induced HGP was markedly increased in hepatocytes co-cultured with KCs and McMΦs from NCD-fed CST-KO mice, and the effect was abrogated upon pre-treatment of CST-KO-MΦs with CST. Thus, we provide a novel mechanism of HGP suppression through CST-mediated inhibition of macrophage infiltration and function.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.2337/db17-0788DOIArticle
http://diabetes.diabetesjournals.org/content/suppl/2018/02/05/db17-0788.DC1PublisherSupplementary Data
Additional Information:© 2018 by the American Diabetes Association. Received July 5, 2017. Accepted January 28, 2018.
Issue or Number:5
Record Number:CaltechAUTHORS:20180220-082141564
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180220-082141564
Official Citation:Catestatin Inhibits Obesity-Induced Macrophage Infiltration and Inflammation in the Liver and Suppresses Hepatic Glucose Production, Leading to Improved Insulin Sensitivity. Wei Ying, Sumana Mahata, Gautam K. Bandyopadhyay, Zhenqi Zhou, Joshua Wollam, Jessica Vu, Rafael Mayoral, Nai-Wen Chi, Nicholas J.G. Webster, Angelo Corti, Sushil K. Mahata. Diabetes May 2018, 67(5) 841-848; DOI: 10.2337/db17-0788
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84884
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:22 Feb 2018 04:44
Last Modified:03 Oct 2019 19:23

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