Dataset Information

Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice.

ABSTRACT: The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and RHMs, or both, represent the major liver inflammatory cell type in obesity. We used a combination of in vivo macrophage tracking methodologies and adoptive transfer techniques in which KCs and RHMs are differentially labeled with fluorescent markers. With these approaches, the inflammatory phenotype of these distinct macrophage populations was determined under lean and obese conditions. In vivo macrophage tracking revealed an approximately sixfold higher number of RHMs in obese mice than in lean mice, whereas the number of KCs was comparable. In addition, RHMs comprised smaller size and immature, monocyte-derived cells compared with KCs. Furthermore, RHMs from obese mice were more inflamed and expressed higher levels of tumor necrosis factor-? and interleukin-6 than RHMs from lean mice. A comparison of the MCP-1/C-C chemokine receptor type 2 (CCR2) chemokine system between the two cell types showed that the ligand (MCP-1) is more highly expressed in KCs than in RHMs, whereas CCR2 expression is approximately fivefold greater in RHMs. We conclude that KCs can participate in obesity-induced inflammation by causing the recruitment of RHMs, which are distinct from KCs and are not precursors to KCs. These RHMs then enhance the severity of obesity-induced inflammation and hepatic insulin resistance.

SUBMITTER: Morinaga H

PROVIDER: S-EPMC4375077 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice.

Morinaga Hidetaka H Mayoral Rafael R Heinrichsdorff Jan J Osborn Olivia O Franck Niclas N Hah Nasun N Walenta Evelyn E Bandyopadhyay Gautam G Pessentheiner Ariane R AR Chi Tyler J TJ Chung Heekyung H Bogner-Strauss Juliane G JG Evans Ronald M RM Olefsky Jerrold M JM Oh Da Young DY

Diabetes 20141014 4

The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and RHMs, or both, represent the major liver inflammatory cell type in obesity. We used a combination of in vivo macrophage tracking methodologies and adoptive transfer techniques in which KCs and RHMs are ...[more]

PMID: 25315009

Similar Datasets

Project description:Zinc-?2-glycoprotein (ZAG) plays an important role in the regulation of body weight, body fat, and glucose metabolism. In this study, we first measured ZAG levels in serum and ZAG mRNA levels in subcutaneous white adipose tissue (sWAT) among overweight/obese patients and lean control subjects. Second, we investigated the effects of ZAG administration on the body weight, body fat and glucose metabolism of high-fat diet (HFD)-induced obese ICR mice and the possible mechanisms involved. The results showed that serum ZAG and mRNA levels in sWAT were significantly decreased in overweight/obese patients and that both showed a negative association with body mass index (BMI) and body weight after adjustment for age and sex. Further partial correlation analysis found that ZAG mRNA expression was positively related with several WAT browning-related genes, including uncoupling protein 1 (UCP1) (r = 0.67) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1a) (r = 0.60), in the sWAT of all subjects. Additionally, intraperitoneal injection of a ZAG expression plasmid (5 ?g/injection, four times a week) in HFD-induced obese mice for 8 weeks demonstrated that ZAG overexpression significantly decreased body weight and WAT mass, and greatly increased the glucose tolerance of obese mice, as shown by the intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT). The staining of UCP1-positive adipocytes was significantly stronger in the sWAT of ZAG-treated obese mice than in that of obese control mice. The mRNA and protein levels of PGC1? in sWAT were significantly increased to 2.2- and 5.3-fold, respectively, compared with HFD obese mice, and there was a strong positive correlation between the expression levels of Zag and Pgc1? in mouse sWAT (r = 0.74). A similar phenomenon was also observed in visceral white adipose tissue (vWAT): the mRNA and protein levels of PGC1? were increased to 1.9- and 3.6-fold, respectively, when obese mice were treated with ZAG. In conclusion, ZAG levels in both sWAT and serum are inversely related with BMI and body weight in Chinese subjects. The action of ZAG on body weight, fat mass and glucose metabolism may be realized through activating PGC1? expression in sWAT and vWAT, then promoting WAT browning in obese mice.

Project description:ObjectivesSafflower yellow (SY) is the main effective ingredient of Carthamus tinctorius L. It has been reported that SY plays an important role in anti-inflammation, anti-platelet aggregation, and inhibiting thrombus formation. In present study, we try to investigate the effects of SY on body weight, body fat mass, insulin sensitivity in high fat diet (HFD)-induced obese mice.MethodsHFD-induced obese male ICR mice were intraperitoneally injected with SY (120 mg kg(-1)) daily. Eight weeks later, intraperitoneal insulin tolerance test (IPITT), and intraperitoneal glucose tolerance test (IPGTT) were performed, and body weight, body fat mass, serum insulin levels were measured. The expression of glucose and lipid metabolic related genes in white adipose tissue (WAT) were determined by RT-qPCR and western blot technologies.ResultsThe administration obese mice with SY significantly reduced the body fat mass of HFD-induced obese mice (P < 0.05). IPITT test showed that the insulin sensitivity of SY treated obese mice were evidently improved. The mRNA levels of insulin signaling pathway related genes including insulin receptor substrate 1(IRS1), PKB protein kinase (AKT), glycogen synthase kinase 3? (GSK3?) and forkhead box protein O1(FOXO1) in mesenteric WAT of SY treated mice were significantly increased to 1.9- , 2.8- , 3.3- , and 5.9-folds of that in HFD-induced control obese mice, respectively (P < 0.05). The protein levels of AKT and GSK3? were also significantly increased to 3.0 and 5.2-folds of that in HFD-induced control obese mice, respectively (P < 0.05). Meanwhile, both the mRNA and protein levels of peroxisome proliferator-activated receptorgamma coactivator 1? (PGC1?) in inguinal subcutaneous WAT of SY group were notably increased to 2.5 and 3.0-folds of that in HFD-induced control obese mice (P < 0.05).ConclusionsSY significantly reduce the body fat mass, fasting blood glucose and increase insulin sensitivity of HFD-induced obese mice. The possible mechanism is to promote the browning of subcutaneous WAT and activate the IRS1/AKT/GSK3? pathway in visceral WAT. Our study provides an important experimental evidence for developing SY as a potential anti-obesity and anti-diabetic drug.

Dataset Information

Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice.

Publications

Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets