The research was conducted using the Web of Science Core Collection (WoSCC). In order to prevent fluctuations in citations brought on by quick publication updates, the literature retrieval was completed in a single day (August 21, 2024). The search formula was set to TS= (macrophage polarization) and TS= (lipid metabolism). The first phase resulted in the acquisition of 474 publications (including early access) issued between 2013 and 2023. Then, 472 publications were included, comprising 351 articles and 121 review articles. Additionally, only English-language articles (n=472) were retained. In order to filter articles that were relevant to our study (lipid metabolism in macrophage polarization), we lastly reviewed the titles, abstracts, or even the whole texts of these publications. A total of 49 publications were excluded via this step. Finally, only 423 studies were enrolled for bibliometrics analysis. The detailed process was shown in Figure 1A . The number of publications and citations, titles, year of publication, countries/regions, affiliations, authors, journals, references, and keywords were all included.

Before analysis, the publications are briefly described as shown in Figure 1B . WOSCC was employed to export all data in the model of “full record and cited references.” Chen (14) developed the bibliometric analysis tool CiteSpace. To get rid of duplicate publications, we imported the “download.txt” file into CiteSpace 6.4.R1 at first. Numerous functions, including illustrating the authors, countries/regions, institutions collaboration, co-cited references, citation burst, keywords co-occurrence, and others, can be realized by it. At the same time, we can rapidly comprehend the growth of knowledge structures, milestone articles, emerging topics, and research hotspots and frontiers thanks to its unique betweenness centrality and bursts analysis. The time slice for our analysis is set to 1 year, the g-index to k = 25. In addition, the parameter settings also include selecting pathfinder, pruning sliced networks, and pruning the merged network. Finally, in the country analysis, we merged the “Peoples R China” and “Taiwan.” Meanwhile, in the keyword analysis, we merged the “macrophage polarization” and “polarization.”

A total of 423 articles and review articles pertaining to macrophage polarization and lipid metabolism were filtered out between 2013 and 2023. Research trends were shown in Figure 1B , which illustrated the yearly increase of publications and citations. In addition, as shown in Figure 1B , the annual publications in this area were relatively low in 2013, 2015, and 2016. And as growing interest focused on lipid metabolism and macrophage polarization, the annual outputs in this field increased steadily and sharply from 2016 to 2023. In 2023, the number of issued articles reached 90, while the citations also reached a peak of 4477. Furthermore, as revealed in Table 1 , the highly cited article issued in 2019 entitled “The metabolic signature of macrophage responses.” The total citations (TC) and total citations per year (TC/Y) were 1082 and 180.33, respectively.

Studies in this area were conducted by 46 countries/regions involving 268 institutions between 2013 and 2023. The top 10 productive countries/regions were displayed in Table 2 . Obviously, China exhibited the most significant number of publications related to lipid metabolism and macrophage polarization (n=173), which was followed by the USA (n=114) and Germany (n=41) in second and third place, respectively. In addition, a further co-authorship network to display the cooperation among countries/regions was mapped, as shown in Figure 2A . Among them, China cooperates most closely with the USA, while France cooperates very frequently with other countries.

And then, Table 3 listed the top 10 productive institutions. Among them, the Centre National de la Recherche Scientifique and the Chinese Academy of Sciences led the outputs, followed by the University of California System. In detail, the Centre National de la Recherche Scientifique has published 15 articles since 2014. And the Chinese Academy of Sciences has published 12 articles since 2015. In addition, there are 9 publications published by the University of California System from 2013. Furthermore, the co-authorship network of institutions demonstrated relatively weak collaboration among them, suggesting that cooperation among institutions needs to be further strengthened ( Figure 2B ).

From 2013 to 2023, a total of 425 authors carried out the studies on lipid metabolism and macrophage polarization. The authors’ cooperation network is shown in Figure 3A .

It is evident that individual author collaboration networks are relatively clustered into clusters, possibly due to a preference for publishing in specific research areas. At the same time, the collaborations among the author clusters also needed to be further strengthened. In addition, the top 20 highly productive authors were summarized in Supplementary Table 1 . The writers with the most publications, as indicated in Supplementary Table 1 , published 3 papers in related topics. These authors include Neyrolles Olivier, Lugo-villarino Geanncarlo, Balboa Luciana, and Bruene Bernhard.

Neyrolles Olivier and Lugo-villarino Geanncarlo have been producing since 2014, while Balboa Luciana and Bruene Bernhard have been publishing since 2018 and 2013, respectively.

Co-cited authors are authors who are cited in articles at the same time. To illustrate the relationships between co-cited authors, a brief network was created ( Figure 3B ). Additionally, Table 4 included a detailed breakdown of the top 10 co-cited authors. Evidently, just 2 authors received more 80 citations, while 7 authors in total were co-cited more than 50 time. Lastly, the top three co-cited authors were MURRAY PJ, ODEGAARD JI, and MANTOVANI A. In detail, MURRAY PJ received 87 citations from 2014, ODEGAARD JI received 84 citations from 2013, and MANTOVANI A received 73 citations from 2013.

One of the CiteSpace’s most distinctive features is the co-citation network, which enables us to comprehend the patterns and development contexts in a certain subject (15). In Figure 4A , the colors go from darker to lighter, indicating that the cited reference is more recent. It is evident that a sizable portion of the referenced sources are recent publications, which is helpful and potent to access the cutting-edge research directions through further literature analysis. In addition, Table 5 displayed the top 10 most cited references in detail. The most cited reference was published by Shapouri-Moghaddam A et al. (16). entitled “Macrophage plasticity, polarization, and function in health and disease.” In this review, the fundamental biology of macrophages, including their origin, differentiation and activation, tissue distribution, migration, and more, is covered in detail in this review. Secondly, it goes over the protective and pathogenic roles of the macrophages in both healthy and unhealthy pregnancies, atherosclerosis, fibrosis, wound healing, autoimmunity, metabolic disease and obesity, anti-microbial defense, anti-tumor immunity, and asthma and allergy. Furthermore, the reference ranked second in citations was written by Jha AK et al., which entitled “Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization.” The systemic alterations during murine M1-like and M2-like macrophage polarization were compiled in this article, with the former highly associated with TCA cycle fragmentation and the latter with activation of glutamine catabolism (17). In the meantime, Tabas I reviewed the latest developments on macrophage polarization and function in various atherosclerosis phases (18), showing that macrophage polarization might be crucial in every stage of this disease. Su P discovered a close connection between the fatty acid oxidation-dependent signaling pathway and human breast, colon, and prostate cancer. He suggested this pathway as a special mechanism that regulates the development and activity of protumor macrophages (19).

Furthermore, the timeline map ( Figure 4B ) was drawn after clustering and named with keywords. Additionally, each cluster’s progress might be more clearly presented. The upcoming trends were shown by clusters 1, 2, 7, and 9. And to note, investigations on the tumor microenvironment in particular are probably going to be an increasingly prevalent topic. Besides, the dense lines between Cluster 1 and Cluster 4 highlight the potential role of aerobic glycolysis in the development of atherosclerosis. Meanwhile, the lines between Cluster 6 and Cluster 8 were also relatively dense, which suggests a close relationship between crown-like structure and lipoprotein. To note, researchers focusing on tumor microenvironment and atherosclerosis are encouraged to enhance interdisciplinary collaboration.

Moreover, a visual map was further constructed to better illustrate the reference burst trend ( Figure 4C ). According to burst analysis, some authors have had a comparatively high number of citations in recent years. For example, the Metabolic Signature of Macrophage Responses was detailed in Viola A’s article, “The Metabolic Signature of Macrophage Responses,” which summarized that M1-like and M2-like macrophages are distinguished by particular pathways that control the metabolism of lipids and amino acids and influence their responses. All of these metabolic adaptations are useful to maintain their polarization in particular situations and to support macrophage activities (20). Besides, the study by Jha AK et al. (2015) got the greatest burst strength (8.07).

First of all, a total of 19 keywords were identified as occurring more than 10 times, which have been illustrated in Figure 5A . As illustrated in Table 6 , “alternative activation,” “inflammation,” “insulin resistance,” and “ppar gamma” were the keywords that appeared most frequently for pathological processes in this field, except for the topic terms of “macrophage polarization” and “lipid metabolism.” And interestingly, we discovered the presence of some keywords (innate immunity and dendritic cells), which may indicate that lipid metabolism mediates close communication between immune cells.

Moreover, keywords after clustering help to characterize the distribution of research content on a specific topic ( Figure 5B ). This led to the creation of a visual representation of keyword co-occurrence clusters. First of all, the cluster’s mean silhouette value was 0.9062 and its modularity Q was 0.7696, respectively, ensuring the high standards of this analysis. Unquestionably, the largest cluster was undoubtedly cluster #0, which was named “progression,” followed by “mycobacterium tuberculosis,” “tumor microenvironment,” “t cell,” “adipose tissue macrophage,” “cholesterol efflux,” and so on. Furthermore, specific representative nodes of each cluster were labeled. Interestingly, tumor microenvironment was the designation given to cluster #2, which included nodes recognized as survival and tumor-associated macrophages. In addition, t cells was the label given to cluster #3, which included nodes recognized as adipose tissue inflammation.

From a timeline perspective, keywords were shown in Figure 6A based on their year of appearance. We performed further analysis of the burst of keyword citations. As illustrated in Figure 6B , “atherosclerosis” got the highest strength. Besides, “nitric oxide” had experienced the most prolonged bursts lasting over four years (2019-2023). Additionally, the most recent burst keywords included “immunometabolism,” “foam cell formation,” and “pathway,” which might represent the current frontiers of research.

Based on the selected literature, we further analyzed the different effects of several metabolites on macrophage polarization and the important enzymes involved in this process ( Table 7 ), in order to thoroughly elucidate the role of lipid metabolism in macrophage polarization. As illustrated in Table 7 , some lipid metabolites, such as palmitic acid, docosahexaenoic acid, prostaglandin E2, arachidonic acid, maresin 1, lysophosphatidylcholine, prostaglandin E3, and 5-aminolevulinate, have a significant impact on macrophage polarization and alter the expression levels of certain proteins. Additionally, it is suggested that PPAR-γ, OXPHOS, kinase A, and CX3CR1 are important enzymes in this process. To note, PPAR-γ seems to be a key enzyme of particular interest.