Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance

Miyachi, Yukihisa; Tsuchiya, Kyoichiro; Komiya, Chikara; Shiba, Kanako; Shimazu, Noriko; Yamaguchi, Shinobu; Deushi, Michiyo; Osaka, Mizuko; Inoue, Kazuo; Sato, Yuta; Matsumoto, Sayaka; Kikuta, Junichi; Wake, Kanako; Yoshida, Masayuki; Ishii, Masaru; Ogawa, Yoshihiro

doi:10.1016/j.celrep.2017.02.039

Cited by 57 publications

(60 citation statements)

References 45 publications

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“…KC depletion by clodronate suppresses the infiltration of monocytes into the liver, potentially due to decreased CCL2 release (53,66); however, these studies are challenging to interpret as clodrolip also depletes monocytes directly. Liver sinusoidal endothelial cells also upregulate VCAM-1 in response to inflammation thereby facilitating adhesion of monocytes (67). Related to this, it has been reported that under lipotoxic stress hepatocytes release extracellular vesicles which are enriched with the integrin ITGβ 1 , a VCAM-1 ligand, which subsequently enhances monocyte adhesion to sinusoidal endothelial cells (68).…”

Section: Macrophages In Obesity and Nafldmentioning

confidence: 91%

The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity

Daemen

Schilling

2020

Front. Immunol.

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Obesity is associated with the development of metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease. The presence of chronic, low-grade inflammation appears to be an important mechanistic link between excess nutrients and clinical disease. The onset of these metabolic disorders coincides with changes in the number and phenotype of macrophages in peripheral organs, particularly in the liver and adipose tissue. Macrophage accumulation in these tissues has been implicated in tissue inflammation and fibrosis, contributing to metabolic disease progression. Recently, the concept has emerged that changes in macrophage metabolism affects their functional phenotype, possibly triggered by distinct environmental metabolic cues. This may be of particular importance in the setting of obesity, where both liver and adipose tissue are faced with a high metabolic burden. In the first part of this review we will discuss current knowledge regarding macrophage dynamics in both adipose tissue and liver in obesity. Then in the second part, we will highlight data linking macrophage metabolism to functional phenotype with an emphasis on macrophage activation in metabolic disease. The importance of understanding how tissue niche influences macrophage function in obesity will be highlighted. In addition, we will identify important knowledge gaps and outstanding questions that are relevant for future research in this area and will facilitate the identification of novel targets for therapeutic intervention in associated metabolic diseases.

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Section: Macrophages In Obesity and Nafldmentioning

confidence: 91%

The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity

Daemen

Schilling

2020

Front. Immunol.

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“…Total RNA was extracted using Qiazol (QIAGEN). cDNA synthesis and quantitative real-time polymerase chain reaction (PCR) were performed as described previously 16 .…”

Section: Methodsmentioning

confidence: 99%

A reduced M1-like/M2-like ratio of macrophages in healthy adipose tissue expansion during SGLT2 inhibition

Miyachi

Tsuchiya

Shiba

et al. 2018

Sci Rep

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The adipose tissue includes various stromal cells, such as preadipocytes, endothelial cells, fibroblasts, and immune cells, which are involved in adipose tissue functions. We previously reported that, in obese mice, the sodium–glucose cotransporter 2 inhibitor ipragliflozin (Ipra) promoted the expansion of the epididymal adipose tissue (Epi) with increase of serum ketone body concentration. The Ipra-induced adipose tissue expansion did not deteriorate adipose inflammation, or systemic glucose/lipid metabolism, referred to as “healthy adipose tissue expansion.” Here we found that Ipra promoted healthy adipose tissue expansion with a reduced ratio of pro-inflammatory M1-like adipose tissue macrophages (ATMs) to anti-inflammatory M2-like ATMs. Ipra downregulated the gene expression of interleukin (IL)−15 (Il15) in stromal cells of Epi. IL-15 inhibited lipogenesis in 3T3-L1 cells associated with downregulation of the lipogenic gene. Ketone body β-hydroxybutyrate suppressed Il15 gene induction in M1-polarized cultured macrophages, and a ketogenic diet reproduced the adipose tissue expansion without deteriorating systemic glucose metabolism in mice. Our data indicate that the phenotypic switch of ATMs could mediate healthy adipose tissue expansion by treatment with Ipra, and it may offer new insights into the pathophysiological mechanisms of adipose tissue expansion.

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“…The latter respond to inflammation or lipid accumulation by upregulating leukocyte adhesion molecules and facilitating VCAM-1/very late antigen-4 (VLA-4)dependent monocyte adhesion and migration. 118 Nevertheless, other chemokine pathways have been identified that also regulate myeloid cell recruitment, including CCL25/CCR9 and CCL1/ CCR8. 119,120 The recruitment of infiltrating monocytederived macrophages is also observed in human fatty liver disease, especially in patients with more advanced stages of fibrosis, where these cells accumulate mainly in clusters around the portal areas.…”

Section: Inflammatory Macrophages Drive Nonalcoholic Fatty Liver Disementioning

confidence: 99%

Macrophages in obesity and non-alcoholic fatty liver disease: Crosstalk with metabolism

2019

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Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and a major cause of liver cirrhosis and hepatocellular carcinoma. NAFLD is intimately linked with other metabolic disorders characterized by insulin resistance. Metabolic diseases are driven by chronic inflammatory processes, in which macrophages perform essential roles. The polarization status of macrophages is itself influenced by metabolic stimuli such as fatty acids, which in turn affect the progression of metabolic dysfunction at multiple disease stages and in various tissues. For instance, adipose tissue macrophages respond to obesity, adipocyte stress and dietary factors by a specific metabolic and inflammatory programme that stimulates disease progression locally and in the liver. Kupffer cells and monocyte-derived macrophages represent ontologically distinct hepatic macrophage populations that perform a range of metabolic functions. These macrophages integrate signals from the gut-liver axis (related to dysbiosis, reduced intestinal barrier integrity, endotoxemia), from overnutrition, from systemic low-grade inflammation and from the local environment of a steatotic liver. This makes them central players in the progression of NAFLD to steatohepatitis (non-alcoholic steatohepatitis or NASH) and fibrosis. Moreover, the particular involvement of Kupffer cells in lipid metabolism, as well as the inflammatory activation of hepatic macrophages, may pathogenically link NAFLD/NASH and cardiovascular disease. In this review, we highlight the polarization, classification and function of macrophage subsets and their interaction with metabolic cues in the pathophysiology of obesity and NAFLD. Evidence from animal and clinical studies suggests that macrophage targeting may improve the course of NAFLD and related metabolic disorders.

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Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance

Cited by 57 publications

References 45 publications

The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity

The Interplay Between Tissue Niche and Macrophage Cellular Metabolism in Obesity

A reduced M1-like/M2-like ratio of macrophages in healthy adipose tissue expansion during SGLT2 inhibition

Macrophages in obesity and non-alcoholic fatty liver disease: Crosstalk with metabolism

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