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7336662 
Journal Article 
Catestatin inhibits obesity-induced macrophage infiltration and inflammation in the liver and suppresses hepatic glucose production, leading to improved insulin sensitivity 
Ying, W; Mahata, S; Bandyopadhyay, GK; Zhou, Z; Wollam, J; Vu, J; Mayoral, R; Chi, NW; Webster, NJG; Corti, A; Mahata, SK 
2018 
Yes 
Diabetes
ISSN: 0012-1797
EISSN: 1939-327X 
American Diabetes Association Inc. 
67 
5 
841-848 
English 
The activation of Kupffer cells (KCs) and monocyte-derived recruited macrophages (McMΦs) in the liver contributes to obesity-induced insulin resistance and type 2 diabetes. Mice with diet-induced obesity (DIO mice) treated with chromogranin A peptide catestatin (CST) showed several positive results. These included decreased hepatic/plasma lipids and plasma insulin, diminished expression of gluconeogenic genes, attenuated expression of proinflammatory 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 proinflammatory in CST-KO NCD mice and produced glucose intolerance, we tested the effects of (sorted with FACS) F4/80+Ly6C- cells (representing KCs) and F4/80-Ly6C+ cells (representing McMΦs) on hepatic glucose production (HGP). Both basal HGP and glucagon-induced HGP were markedly increased in hepatocytes cocultured with KCs and McMΦs from NCD-fed CST-KO mice, and the effect was abrogated upon pretreatment of CST-KO macrophages with CST. Thus, we provide a novel mechanism of HGP suppression through CST-mediated inhibition of macrophage infiltration and function. © 2018 by the American Diabetes Association. 
catestatin; fat droplet; fatty acid; gamma interferon; glucose 6 phosphatase; insulin; interleukin 1beta; interleukin 6; monocyte chemotactic protein 1; phosphoenolpyruvate carboxykinase (GTP); triacylglycerol; chromogranin A; chromogranin A (344-364); glucagon; glucose; hormone; insulin; peptide fragment; animal; animal cell; animal experiment; animal model; antigen presenting cell; Article; body weight; cell infiltration; cell vacuole; chemotaxis assay; coculture; diet induced obesity; epididymis fat; fluorescence activated cell sorting; food intake; gene expression; gluconeogenesis; glucose assay; glucose intolerance; glucose tolerance; hepatic glucose production; immunoassay; in vitro study; insulin blood level; insulin sensitivity; insulin tolerance test; Kupffer cell; lipid diet; lipid liver level; lipid storage; liver; liver cell; liver weight; macrophage; monocyte; monocyte derived recruited macrophage; mouse; nonhuman; priority journal; real time polymerase chain reaction; transmission electron microscopy; drug effect; gene expression regulation; genetics; gluconeogenesis; immunology; inflammation; insulin resistance; knockout mouse; lipid metabolism; liver; macrophage; male; metabolism; obesity; Animals; Chromogranin A; Gene Expression Regulation; Glucagon; Gluconeogenesis; Glucose; Hormones; Inflammation; Insulin; Insulin Resistance; Kupffer Cells; Lipid Metabolism; Liver; Macrophages; Male; Mice; Mice, Knockout; Obesity; Peptide Fragments