Enhanced M2 macrophage polarization in high n‐3 polyunsaturated fatty acid transgenic mice fed a high‐fat diet

Song, Mi‐Young; Wang, Jie; Lee, Youngyi; Lee, Juhyung; Kwon, Keun-Sang; Bae, Eun Ju; Park, Byung‐Hyun

doi:10.1002/mnfr.201600014

Cited by 26 publications

(26 citation statements)

References 40 publications

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“…A high‐fat diet (HFD) promotes progenitor proliferation and adipogenesis in adipose tissue in rodents prior to a significant increase of body weight . Our results showed that the relative percentage of M1 macrophages in WT‐SVF was about 12% of total SVF compared with a previous study in which nearly 40% was observed when WT mice had a significant body weight gain relative to Fat‐1 mice in an HFD‐induced obesity model . Without HFD challenge, no body weight difference between WT and Fat‐1 mice at the age of 9 to 12 weeks was observed in this study, thus indicating that the mice used for WAP identification were not yet in an obese state; most likely, their adipose tissue was prone to hyperplasia after HFD feeding.…”

Section: Discussioncontrasting

confidence: 44%

“…Moreover, previous studies have reported potential adverse effects of inhibiting adipogenesis on metabolism . However, this is not the case for the effects of omega‐3 PUFA . Herein, omega‐3 PUFA reduced the WAP resident population rather than completely abolished WAP numbers and their differentiation to white adipocytes.…”

Section: Discussionmentioning

confidence: 75%

“…Additionally, the literature has shown that omega‐3 PUFA can attenuate obesity, increase insulin sensitivity, and improve diabetes‐associated metabolic syndromes through inhibition of lipogenesis, suppression of inflammation, etc. . It is obvious that omega‐3 PUFA can inhibit adipogenesis without causing metabolic dysfunction.…”

Section: Discussionmentioning

confidence: 99%

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Endogenous Omega‐3 Polyunsaturated Fatty Acids Reduce the Number and Differentiation of White Adipocyte Progenitors in Mice

Chen

Kang

2019

Obesity

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OBESITY BIOLOGY AND INTEGRATED PHYSIOLOGY Study ImportanceWhat is already known? ► Omega-3 fatty acids are known to have antiobesity effects in mice. ► Mechanisms shown for these effects in mice include reducing chronic inflammation, increasing thermogenesis, modulating the gut microbiome, and improving lipid metabolism. What does this study add?► This study demonstrates a new mechanism -omega-3 fatty acids suppress adipogenesis by reducing the number and differentiation of white adipocyte progenitors in mice.Objectives: Reducing the increased number of white adipocyte progenitors (WAP) is considered a novel approach to controlling obesity. The role of omega-3 polyunsaturated fatty acids (PUFA) in regulating the WAP resident population is unclear. The objective of this study was to investigate the effect of omega-3 PUFA on the niche composition of adiposederived stem cells.Methods: Stromal vascular cell fraction (SVF) was collected from subcutaneous fat of wild-type (WT) and transgenic mice carrying a fat-1 gene from Caenorhabditis elegans (Fat-1 mice), which are capable of synthesizing omega-3 PUFA and have much higher tissue levels of omega-3 PUFA relative to WT mice. The isolated SVF cells were cultured and used for the examination of adipocyte differentiation, adipogenic markers, fatty acid composition, and WAP numbers. Results: SVF isolated from Fat-1 mice (Fat-1-SVF) exhibited markedly fewer differentiated adipocytes with smaller cell size and less lipid content than that of WT mice (WT-SVF). Accordingly, adipogenesis-related genes and the white adipocyte surface marker ASC-1 were downregulated in Fat-1-SVF relative to WT-SVF. Furthermore, WAP numbers and adipose tissue macrophages were lower in Fat-1-SVF than WT-SVF. Conclusions: Omega-3 PUFA can both limit the WAP resident population and suppress their differentiation to white adipocytes, suggesting a new mechanism for the antiobesity effect of omega-3 PUFA.Obesity (2020) 28, 235-240.

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Section: Discussioncontrasting

confidence: 44%

Section: Discussionmentioning

confidence: 75%

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Endogenous Omega‐3 Polyunsaturated Fatty Acids Reduce the Number and Differentiation of White Adipocyte Progenitors in Mice

Chen

Kang

2019

Obesity

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“…There are limited data on the relationship between oxylipins and various cell polarization and/or adaptation states. Recently, it was shown that various ω-3/ω-6 PUFA diets are able to change the polarization of macrophages [7,8]. There is also evidence that ω-6and ω-3-derived oxylipins are able to modulate the inflammatory phenotype of immune cells, especially macrophages [7,9].…”

Section: Introductionmentioning

confidence: 99%

Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

Chistyakov

Gavrish

Goriainov

et al. 2020

IJMS

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Functional phenotypes, which cells can acquire depending on the microenvironment, are currently the focus of investigations into new anti-inflammatory therapeutic approaches. Glial cells, microglia, and astrocytes are major participants in neuroinflammation, but their roles differ, as microglia are cells of mesodermal origin, while astrocytes are cells of ectodermal origin. The inflammatory phenotype of cells can be modulated by ω-6- and ω-3-polyunsaturated fatty acid-derived oxylipins, although data on changes in oxylipin profiles in different cell adaptations to pro- and anti-inflammatory stimuli are scarce. Our study aimed to compare UPLC-MS/MS-measured oxylipin profiles in various rat astrocyte adaptation states. We used cells treated for 24 h with lipopolysaccharide (LPS) for classical pro-inflammatory adaptation and with interleukin 4 (IL-4) or 10 (IL-10) for alternative anti-inflammatory adaptation, with the resulting phenotypes characterized by quantitative real-time PCR (RT-PCR). We also tested long-term, low-concentration LPS treatment (endotoxin treatment) as a model of astrocyte adaptations. The functional response of astrocytes was estimated by acute (4 h) LPS-induced cell reactivity, measured by gene expression markers and oxylipin synthesis. We discovered that, as well as gene markers, oxylipin profiles can serve as markers of pro- (A1-like) or anti-inflammatory (A2-like) adaptations. We observed predominant involvement of ω-6 polyunsaturated fatty acid (PUFA) and the cyclooxygenase branch for classical (LPS) pro-inflammatory adaptations and ω-3 PUFA and the lipoxygenase branch for alternative (IL-4) anti-inflammatory adaptations. Treatment with IL-4, but not IL-10, primes the ability of astrocytes to activate the innate immunity signaling pathways in response to LPS. Endotoxin-treated astrocytes provide an alternative anti-inflammatory adaptation, which makes cells less sensitive to acute LPS stimulation than the IL-4 induced adaptation. Taken together, the data reveal that oxylipin profiles associate with different states of polarization to generate a pro-inflammatory or anti-inflammatory phenotype. This association manifests itself both in native cells and in their responses to a pro-inflammatory stimulus.

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“…Saturated fatty acids are commonly proinflammatory, whereas unsaturated fatty acids are weakly proinflammatory or neutral, and v-3 polyunsaturated fatty acids (PUFAs), such as a-linolenic acid (ALA), eicosapentaenoic acid, and docosahexaenoic acid are anti-inflammatory (5,6). Several anti-inflammatory effects of v-3 PUFAs have been characterized in terms of macrophage function (7)(8)(9), although the underlying mechanisms remain poorly understood.…”

mentioning

confidence: 99%

α‐Linolenic acid‐derived metabolites from gut lactic acid bacteria induce differentiation of anti‐inflammatory M2 macrophages through G protein‐coupled receptor 40

et al. 2017

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Among dietary fatty acids with immunologic effects, ω-3 polyunsaturated fatty acids, such as α-linolenic acid (ALA), have been considered as factors that contribute to the differentiation of M2-type macrophages (M2 macrophages). In this study, we examined the effect of ALA and its gut lactic acid bacteria metabolites 13-hydroxy-9(),15()-octadecadienoic acid (13-OH) and 13-oxo-9(),15()-octadecadienoic acid (13-oxo) on the differentiation of M2 macrophages from bone marrow-derived cells (BMDCs) and investigated the underlying mechanisms. BMDCs were stimulated with ALA, 13-OH, or 13-oxo in the presence of IL-4 or IL-13 for 24 h, and significant increases in M2 macrophage markers CD206 and Arginase-1 (Arg1) were observed. In addition, M2 macrophage phenotypes were less prevalent following cotreatment with GPCR40 antagonists or inhibitors of PLC-β and MEK under these conditions, suggesting that GPCR40 signaling is involved in the regulation of M2 macrophage differentiation. In further experiments, remarkable M2 macrophage accumulation was observed in the lamina propria of the small intestine of C57BL/6 mice after intragastric treatments with ALA, 13-OH, or 13-oxo at 1 g/kg of body weight per day for 3 d. These findings suggest a novel mechanism of M2 macrophage differentiation involving fatty acids from gut lactic acid bacteria and GPCR40 signaling.-Ohue-Kitano, R., Yasuoka, Y., Goto, T., Kitamura, N., Park, S.-B., Kishino, S., Kimura, I., Kasubuchi, M., Takahashi, H., Li, Y., Yeh, Y.-S., Jheng, H.-F., Iwase, M., Tanaka, M., Masuda, S., Inoue, T., Yamakage, H., Kusakabe, T., Tani, F., Shimatsu, A., Takahashi, N., Ogawa, J., Satoh-Asahara, N., Kawada, T. α-Linolenic acid-derived metabolites from gut lactic acid bacteria induce differentiation of anti-inflammatory M2 macrophages through G protein-coupled receptor 40.

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Enhanced M2 macrophage polarization in high n‐3 polyunsaturated fatty acid transgenic mice fed a high‐fat diet

Abstract: Our results indicate that n-3 PUFAs play a crucial role in macrophage polarization and chemotaxis, and thus regulate the development of HFD-induced tissue inflammation and metabolic derangements.

Cited by 26 publications

References 40 publications

Endogenous Omega‐3 Polyunsaturated Fatty Acids Reduce the Number and Differentiation of White Adipocyte Progenitors in Mice

Endogenous Omega‐3 Polyunsaturated Fatty Acids Reduce the Number and Differentiation of White Adipocyte Progenitors in Mice

Oxylipin Profiles as Functional Characteristics of Acute Inflammatory Responses in Astrocytes Pre-Treated with IL-4, IL-10, or LPS

α‐Linolenic acid‐derived metabolites from gut lactic acid bacteria induce differentiation of anti‐inflammatory M2 macrophages through G protein‐coupled receptor 40

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