Peritoneal macrophages have an impaired immune response in obesity which can be reversed by subsequent weight loss

Willemsen, Lisa; Neele, Annette E.; Velden, Saskia van der; Prange, K.H.M.; Toom, Myrthe den; Roomen, Cindy P. A. A. van; Reiche, Myrthe E.; Griffith, Guillermo R.; Gijbels, Marion J.J.; Lutgens, Esther; Winther, Menno P.J. de

doi:10.1136/bmjdrc-2019-000751

Cited by 10 publications

(5 citation statements)

References 55 publications

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“…Peritoneal macrophages from the diet-induced obesity model do not display foam cell characteristics, although they exhibit downregulation of several enzymes of the cholesterol biosynthesis pathway, including Dhcr24 [122]. Accumulation of desmosterol in macrophages from diet-induced obesity mice is also associated with upregulation of LXR and SREPB target genes and downregulation of inflammatory genes [122].…”

Section: Metabolic Changes In Peripheral Macrophages In the Context Of Obesitymentioning

confidence: 97%

“…Downregulation of Dhcr24 results in accumulation of desmosterol that activates LXR and SREBP target genes, interferes with FA metabolism, and contributes to impaired inflammatory responses in macrophages from hypercholesterolemic mice [121]. Peritoneal macrophages from the diet-induced obesity model do not display foam cell characteristics, although they exhibit downregulation of several enzymes of the cholesterol biosynthesis pathway, including Dhcr24 [122]. Accumulation of desmosterol in macrophages from diet-induced obesity mice is also associated with upregulation of LXR and SREPB target genes and downregulation of inflammatory genes [122].…”

Section: Metabolic Changes In Peripheral Macrophages In the Context Of Obesitymentioning

confidence: 99%

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Metabolic Regulation of Macrophage Activation

et al. 2021

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Macrophages, the central mediators of innate immune responses, being in the first-line of defense, they have to readily respond to pathogenic or tissue damage signals to initiate the inflammatory cascade. Such rapid responses require energy to support orchestrated production of pro-inflammatory mediators and activation of phagocytosis. Being a cell type that is present in diverse environments and conditions, macrophages have to adapt to different nutritional resources. Thus, macrophages have developed plasticity and are capable of utilizing energy at both normoxic and hypoxic conditions and in the presence of varying concentrations of glucose or other nutrients. Such adaptation is reflected on changes in signaling pathways that modulate responses, accounting for the different activation phenotypes observed. Macrophage metabolism has been tightly associated with distinct activation phenotypes within the range of M1-like and M2-like types. In the context of diseases, systemic changes also affect macrophage metabolism, as in diabetes and insulin resistance, which results in altered metabolism and distinct activation phenotypes in the adipose tissue or in the periphery. In the context of solid tumors, tumor-associated macrophages adapt in the hypoxic environment, which results in metabolic changes that are reflected on an activation phenotype that supports tumor growth. Coordination of environmental and pathogenic signals determines macrophage metabolism, which in turn shapes the type and magnitude of the response. Therefore, modulating macrophage metabolism provides a potential therapeutic approach for inflammatory diseases and cancer.

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Section: Metabolic Changes In Peripheral Macrophages In the Context Of Obesitymentioning

confidence: 97%

Section: Metabolic Changes In Peripheral Macrophages In the Context Of Obesitymentioning

confidence: 99%

Metabolic Regulation of Macrophage Activation

et al. 2021

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“…Finally, preclinical evaluation of novel biomaterials must take into account that the inflammatory response is affected by patient-specific factors that may not be adequately represented by animal models. For example, at least 40% of the U.S. population is obese or diabetic, with major effects on immune cell behavior, − but the efficacy of biomaterials is not typically evaluated in obese or diabetic animals. As examples of how heterogeneity in the human immune response can influence the failure of biomaterials, 28% of breast implants require revision, and successful biomaterials in diabetic wound healing are successful in only around 55% of cases. , Similarly, total joint replacements fail after a wide range of implant duration, ranging from 15 to 25 years on average .…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

Immunomodulatory Biomaterials for Tissue Repair

et al. 2021

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All implanted biomaterials are targets of the host’s immune system. While the host inflammatory response was once considered a detrimental force to be blunted or avoided, in recent years, it has become a powerful force to be leveraged to augment biomaterial–tissue integration and tissue repair. In this review, we will discuss the major immune cells that mediate the inflammatory response to biomaterials, with a focus on how biomaterials can be designed to modulate immune cell behavior to promote biomaterial–tissue integration. In particular, the intentional activation of monocytes and macrophages with controlled timing, and modulation of their interactions with other cell types involved in wound healing, have emerged as key strategies to improve biomaterial efficacy. To this end, careful design of biomaterial structure and controlled release of immunomodulators can be employed to manipulate macrophage phenotype for the maximization of the wound healing response with enhanced tissue integration and repair, as opposed to a typical foreign body response characterized by fibrous encapsulation and implant isolation. We discuss current challenges in the clinical translation of immunomodulatory biomaterials, such as limitations in the use of in vitro studies and animal models to model the human immune response. Finally, we describe future directions and opportunities for understanding and controlling the biomaterial–immune system interface, including the application of new imaging tools, new animal models, the discovery of new cellular targets, and novel techniques for in situ immune cell reprogramming.

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“…On the level of the adipose tissue, weight loss has been shown to reduce the chronic inflammatory state of the adipose tissue. 105 However, weight loss does not completely normalize the inflammatory state since several immune markers remain elevated after weight loss. 106 , 107 This so-called ‘obesogenic memory’ is characterized by an increase in pro-inflammatory macrophages that fail to normalize in number and phenotype after weight loss.…”

Section: Trained Immunity In Ascvdmentioning

confidence: 99%

Innate immune memory in cardiometabolic disease

Bahrar

Bekkering

Stienstra

et al. 2023

Cardiovascular Research

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Low-grade systemic inflammation is a key pathophysiological component of atherosclerotic cardiovascular disease (CVD), and long-term activation of myeloid cells is thought to be crucial for these effects. Obesity and associated metabolic complications including hyperglycaemia and dyslipoproteinaemia can induce long-lasting inflammatory reprogramming of the innate immune cells and their bone marrow progenitors, which in turn contributes to atherosclerosis. In this review, we discuss the mechanisms through which innate immune cells undergo long-term changes in their functional, epigenetic, and metabolic characteristics upon even short-term exposure to endogenous ligands, a process also termed ‘trained immunity’. Inappropriate induction of trained immunity leads to the development of long-lasting hyperinflammatory and proatherogenic changes in monocytes and macrophages, an important factor in the development of atherosclerosis and CVDs. Knowledge of the specific immune cells and the distinct intracellular molecular pathways involved in the induction of trained immunity will reveal novel pharmacological targets that could be used to prevent or treat CVDs in the future.

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Peritoneal macrophages have an impaired immune response in obesity which can be reversed by subsequent weight loss

Cited by 10 publications

References 55 publications

Metabolic Regulation of Macrophage Activation

Metabolic Regulation of Macrophage Activation

Immunomodulatory Biomaterials for Tissue Repair

Innate immune memory in cardiometabolic disease

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