Honokiol attenuates diet‐induced non‐alcoholic steatohepatitis by regulating macrophage polarization through activating peroxisome proliferator‐activated receptor γ

Zhong, Xueqing; Liu, Hailin

doi:10.1111/jgh.13853

Cited by 51 publications

(29 citation statements)

References 41 publications

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“…Recent studies have indicated that macrophages/Kupffer cells participate in lipid homeostasis in NAFLD. Animal studies have shown that M1 Kupffer cells increase hepatic lipid deposition, 39, 40 while M2 activation of Kupffer cells can ameliorate obesity‐induced insulin resistance and hepatic steatosis 41 . Furthermore, the promotion of hepatic M2 macrophage polarization was accompanied by attenuated hepatic lipid accumulation 42 .…”

Section: Discussionmentioning

confidence: 99%

Regulation of lipid‐induced macrophage polarization through modulating peroxisome proliferator‐activated receptor‐gamma activity affects hepatic lipid metabolism via a Toll‐like receptor 4/NF‐κB signaling pathway

et al. 2020

J of Gastro and Hepatol

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Background and Aim Chronic inflammation links closely to insulin resistance and lipid metabolism in nonalcoholic fatty liver disease (NAFLD). Macrophage M1 activation plays an important role in the initiation and continuing of pro‐inflammatory response of NAFLD. Our study was to investigate whether macrophage M1/M2 polarization switching would affect hepatic inflammation and lipid metabolism through modulation of peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) activity in vivo and in vitro. Methods RAW264.7 macrophages were treated with different fatty acids, and cell culture supernatants were collected to prepare conditioned media (CM). Different co‐culture systems between primary hepatocytes and CM from macrophages were established. A PPAR‐γ agonist or antagonist was administered to regulate PPAR‐γ activity and macrophage polarization. M1/M2 phenotype markers, inflammatory signaling pathway, and lipid‐related genes expression were determined. Wild‐type C57BL/6 mice were fed a high‐fat diet to induce NAFLD and given rosiglitazone to regulate PPAR‐γ activity in vivo. Results Saturated fatty acids induced M1‐polarized macrophages while polyunsaturated fatty acids induced M2‐polarized macrophages. M1‐polarized macrophages significantly promoted lipid synthesis and accumulation in primary hepatocytes through upregulation of a toll‐like receptor 4 (TLR4)/NF‐κB signaling pathway. The PPAR‐γ agonist made lipid‐induced M1‐polarized macrophages switch to an M2‐predominant phenotype, while PPAR‐γ antagonist had the opposite effect. Macrophage polarization shifting subsequently affected lipid metabolism in primary hepatocytes. Administration of rosiglitazone improved high‐fat diet induced hepatic steatosis and lipid metabolism through reducing hepatic TLR4/NF‐κB expression and M1‐polarized Kupffer cells. Conclusions Lipid‐induced macrophage M1 polarization promoted hepatic lipid metabolism. Modulation of PPAR‐γ activity could shift macrophage polarization and subsequently affect lipid metabolism. Upregulation of the TLR4/NF‐κB signaling pathway is closely linked to dysregulated lipid metabolism in NAFLD.

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Section: Discussionmentioning

confidence: 99%

Regulation of lipid‐induced macrophage polarization through modulating peroxisome proliferator‐activated receptor‐gamma activity affects hepatic lipid metabolism via a Toll‐like receptor 4/NF‐κB signaling pathway

et al. 2020

J of Gastro and Hepatol

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“…While most research suggests pro-inflammatory Mϕs dominate in NAFLD and drive disease pathogenesis, hepatic Mϕs may also have anti-inflammatory properties. Moreover, promoting such M2-like Mϕs has been reported to be beneficial for protecting against NAFLD [177] , [179] , [180] , [181] , [182] , [183] . Taken together, these results suggest that manipulation of the M1/M2 ratio in NAFLD may be an attractive therapeutic strategy [184] .…”

Section: Transcription Factors Modulating Lipid Metabolism Activity Imentioning

confidence: 99%

Macrophages and lipid metabolism

Remmerie

Scott

2018

Cellular Immunology

333

252

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“…All three PPAR family members have been shown to play a role in mouse macrophage polarization. PPARα, β, or γ activation was demonstrated to potentiate the polarization of mouse macrophages towards the anti-inflammatory M2 phenotype, while M2-type responses are compromised in the absence of PPARγ or β expression (effect of PPARα absence has not been studied) [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. In human macrophages results are less clear-cut; while PPARγ activation has been shown to stimulate M2 polarization, PPARα or β activation did not seem to have any effect [ 67 , 68 , 69 , 70 , 71 ].…”

Section: Role Of Ppars In Immune Cell Functionmentioning

confidence: 99%

Regulation of Immune Cell Function by PPARs and the Connection with Metabolic and Neurodegenerative Diseases

Menn

Neels

2018

IJMS

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Increasing evidence points towards the existence of a bidirectional interconnection between metabolic disease and neurodegenerative disorders, in which inflammation is linking both together. Activation of members of the peroxisome proliferator-activated receptor (PPAR) family has been shown to have beneficial effects in these interlinked pathologies, and these improvements are often attributed to anti-inflammatory effects of PPAR activation. In this review, we summarize the role of PPARs in immune cell function, with a focus on macrophages and T cells, and how this was shown to contribute to obesity-associated inflammation and insulin resistance, atherosclerosis, and neurodegenerative disorders. We address gender differences as a potential explanation in observed contradictory results, and we highlight PPAR-induced metabolic changes as a potential mechanism of regulation of immune cell function through these nuclear receptors. Together, immune cell-specific activation of PPARs present a promising therapeutic approach to treat both metabolic and neurodegenerative diseases.

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Honokiol attenuates diet‐induced non‐alcoholic steatohepatitis by regulating macrophage polarization through activating peroxisome proliferator‐activated receptor γ

Abstract: Honokiol can attenuate CL diet-induced NASH and the mechanism in which possibly is polarizing macrophages to M2 phenotype via PPARγ activation.

Cited by 51 publications

References 41 publications

Regulation of lipid‐induced macrophage polarization through modulating peroxisome proliferator‐activated receptor‐gamma activity affects hepatic lipid metabolism via a Toll‐like receptor 4/NF‐κB signaling pathway

Regulation of lipid‐induced macrophage polarization through modulating peroxisome proliferator‐activated receptor‐gamma activity affects hepatic lipid metabolism via a Toll‐like receptor 4/NF‐κB signaling pathway

Macrophages and lipid metabolism

Regulation of Immune Cell Function by PPARs and the Connection with Metabolic and Neurodegenerative Diseases

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