Effects of des-acyl ghrelin on insulin sensitivity and macrophage polarization in adipose tissue

Abstract

Background and Objectives Obesity is the accumulation of adipose tissue caused by excess energy in the body, accompanied by long-term chronic low-grade inflammation of adipose tissue. More than 50% of interstitial cells in adipose tissue are macrophages, which produce cytokines closely related to insulin resistance. Macrophage biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2 (anti-inflammatory). This study aimed to investigate the effect of gastric hormone des-acyl ghrelin (DAG) on the polarization phenotype of macrophages and elucidate the role of macrophages in adipose tissue inflammation and insulin sensitivity and its molecular mechanism. Methods Mice were subcutaneously administrated with DAG in osmotic minipumps. The mice were fed a normal diet or a high-fat diet (HFD). Different macrophage markers were detected by real-time revere transcription polymerase chain reaction. Results Exogenous administration of DAG significantly inhibited the increase of adipocyte volume caused by HFD and reduced the number of rosette-like structures in adipose tissue. HFD in the control group significantly increased M1 macrophage markers, tumor necrosis factor α (TNFα), and inducible NO synthase (iNOS). However, these increases were reduced or even reversed after DAG administration in vitro. The M2 markers, macrophage galactose type C-type Lectin-1 (MGL1), arginase 1 (Arg1), and macrophage mannose receptor 1 (MRC1) were decreased by HFD, and the downward trend was inhibited or reversed after DAG administration. Although Arg1 was elevated after HFD, the fold increase after DAG administration in vitro was much greater than that in the control group. Conclusion DAG inhibits adipose tissue inflammation caused by HFD, reduces infiltration of macrophages in adipose tissue, and promotes polarization of macrophages to M2, thus alleviating obesity and improving insulin sensitivity.

Relationship Between Acyl and Desacyl Ghrelin Levels with Insulin Resistance and Body Fat Mass in Type 2 Diabetes Mellitus

“…Previous observations have shown that obese mice and humans have lower DAG levels than their normal-weight counterparts where AG levels are similar, suggesting that obesity may reflect a relative DAG deficiency 8 , 35 , 36 Our study found that compared with VFA normal group, VFA obese individuals with high or normal BMI have lower DAG levels and higher HOMA-IR. VFA was significantly negatively correlated with DAG levels.…”

“… 37 Besides, DAG can inhibit inflammation of adipose tissue caused by HFD and decrease macrophage infiltration of adipose tissue, thus alleviating obesity and improving insulin sensitivity in rodents. 36 In contrast, administering AG reduces energy expenditure, enhances gene expression of fat storage-promoting enzymes in adipose tissue, and consequently promotes adipose tissue deposition in animal models. 38 No correlation between AG concentrations and body fat mass was found in the study.…”

Single-cell transcriptome landscape of zebrafish liver reveals hepatocytes and immune cell interactions in understanding nonalcoholic fatty liver disease

“…Studies in humans have shown that there are two subtypes of human liver macrophages, which segregate into proinflammatory and immunoregulatory phenotypes( 23 ). In our study, m rc1b ( 95 ), hmoxla ( 96 ), marco and cd63 ( 97 ) were placed in non-inflammatory macrophages in zebrafish liver, and these genes are known marker genes for immunoregulatory macrophages. It has been suggested that zebrafish liver non-inflammatory macrophages are similar to the profiles of CD68 + MARCO + cells in the human liver and that of resident Kupffer cells (KCs) in the rodent liver.…”

lncRNA ZFAS1 Positively Facilitates Endothelial Ferroptosis via miR-7-5p/ACSL4 Axis in Diabetic Retinopathy

“…Among the current treatments of DR, the first and foremost is controlling blood sugar. Multiple evidence has pointed out that changing lifestyle, ameliorating insulin resistance, and repairing damaged β islet cell function can effectively delay the occurrence of DR [57][58][59]. DR is now recognized as a neuro-and vaso-degenerative rather than a microvascular disease, even in early stage when neuron loss is not evident [60,61].…”