Resolvin D1 reduces inflammation in co-cultures of primary human macrophages and adipocytes by triggering macrophages

Gemperle, Corinne; Tran, Syndi; Schmid, Mattia; Rimann, Nicole; Marti-Jaun, Jacqueline; Hartling, Ivan; Hersberger, Martin

doi:10.1016/j.plefa.2021.102363

Cited by 11 publications

(11 citation statements)

References 54 publications

(98 reference statements)

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“…These results are consistent with the literature that one mechanism of action for resolvins is through the targeting of differing aspects of white adipose tissue metabolism and inflammation 27 . For instance, resolvin D1 and D2 treatment of adipocytes or in a co‐culture model with macrophages led to reduced leptin levels in obese mice 17,28 . In addition, several studies show that differing SPMs can improve aspects of insulin resistance 29–32 …”

Section: Discussionsupporting

confidence: 90%

“…27 For instance, resolvin D1 and D2 treatment of adipocytes or in a co-culture model with macrophages led to reduced leptin levels in obese mice. 17,28 In addition, several studies show that differing SPMs can improve aspects of insulin resistance. [29][30][31][32] Thus, these results set the basis for studying why specific DO mice are positive responders to RvE1.…”

Section: Discussionmentioning

confidence: 99%

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Modeling human heterogeneity of obesity with diversity outbred mice reveals a fat mass‐dependent therapeutic window for resolvin E1

et al. 2022

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Resolvin E1 (RvE1), a specialized pro‐resolving mediator (SPM), improves glucose homeostasis in inbred mouse models of obesity. However, an impediment toward translation is that obesity is a highly heterogenous disease in which individuals will respond very differently to interventions such as RvE1. Thus, there is a need to study SPMs in the context of modeling the heterogeneity of obesity that is observed in humans. We investigated how RvE1 controls the concentration of key circulating metabolic biomarkers using diversity outbred (DO) mice, which mimic human heterogeneity. We first demonstrate that weights of DO mice can be classified into distinct distributions of fat mass (i.e., modeling differing classes of obesity) in response to a high‐fat diet and in the human population when examining body composition. Next, we show RvE1 administration based on body weight for four consecutive days after giving mice a high‐fat diet led to approximately half of the mice responding positively for serum total gastric inhibitory polypeptide (GIP), glucagon, insulin, glucose, leptin, and resistin. Interestingly, RvE1 improved hyperleptinemia most effectively in the lowest class of fat mass despite adjusting the dose of RvE1 with increasing adiposity. Furthermore, leptin levels after RvE1 treatment were the lowest in those mice that were also RvE1 positive responders for insulin and resistin. Collectively, these results suggest a therapeutic fat mass‐dependent window for RvE1, which should be considered in future clinical trials. Moreover, the data underscore the importance of studying SPMs with heterogenous mice as a step toward precision SPM administration in humans.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Modeling human heterogeneity of obesity with diversity outbred mice reveals a fat mass‐dependent therapeutic window for resolvin E1

et al. 2022

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“…54 Improving this ratio by increasing the dietary ω-3 fatty acids is known to improve the inflammatory tone of the tissue 55,56 (this phenomenon is also observed in OA 57,58 ). Reports also suggest that RvD1 (an ω-3 fatty acid) reduces the levels of leptin in adipocytes in vitro, 59 F I G U R E 4 Lipo-RvD1 treated mice show reduced synovitis. thus promoting healthy adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

Sustained release resolvin D1 liposomes are effective in the treatment of osteoarthritis in obese mice

Dravid

Dhanabalan

Naskar

et al. 2023

J Biomedical Materials Res

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Osteoarthritis (OA) is the most common joint disorder and currently affects >500 million patients worldwide, with ~60% of them also suffering from obesity. There is no drug approved for human use that changes the course of OA progression. OA is one of the most common comorbidities of obesity, and obesity‐related OA (ObOA) is a serious health concern because it shows heightened severity of tissue damage and also predominantly affects the working population. Unresolved inflammation is a major driver of ObOA, thus, resolving disease‐associated inflammation is a viable strategy to treat ObOA. Resolvins are highly potent molecules that play a role in the resolution of inflammation and promote tissue healing. However, small molecules (like Resolvin D1; RvD1) have to be administered frequently or prior to injury because they lose their in vivo activity rapidly either by lymphatic clearance, or oxidation‐mediated deactivation. In this study, we have encapsulated RvD1 in liposomes and established its efficacy in the mouse model of ObOA at much lower dosages than freely administered RvD1. Liposomal RvD1 (lipo‐RvD1) acted as a source of the RvD1 molecules for ~11 days in vitro in synovial fluid derived from patients. When administered prophylactically or therapeutically, lipo‐RvD1 suppressed cartilage damage in male C57BL/6 mice compared to untreated and free RvD1 treatments. This efficacy was achieved by increasing the proportion of the proresolution M2 macrophages over proinflammatory M1 macrophages in the synovial membrane. These results show the potential of lipo‐RvD1 as an anti‐OA agent.

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“…Improving this ratio by increasing the dietary ω-3 fatty acids is known to improve the inflammatory tone of the tissue 55,56 (this phenomenon is also observed in OA 57, 58 ). Reports also suggest that RvD1 (an ω-3 fatty acid) reduces the levels of leptin in adipocytes in vitro 59 , thus promoting healthy adipose tissue. We had previously shown that administration of lipo-RvD1 was efficacious in chow-fed mice 16 .…”

Section: Discussionmentioning

confidence: 99%

Sustained release Resolvin D1 liposomes are effective in the treatment of osteoarthritis in obese mice

Dravid

Dhanabalan

Naskar

et al. 2023

Preprint

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Osteoarthritis (OA) is the most common joint disorder and currently affects > 500 million patients worldwide, with ~60% of them also suffering from obesity. There is no drug approved for human use that changes the course of OA progression. OA is one of the most common comorbidities of obesity, and obesity-related OA (ObOA) is a serious health concern because it shows heightened severity of tissue damage and also predominantly affects the working population. Unresolved inflammation is a major driver of ObOA, thus, resolving disease-associated inflammation is a viable strategy to treat ObOA. Resolvins are highly potent molecules that play a role in the resolution of inflammation and promote tissue healing. However, small molecules (like Resolvin D1; RvD1) have to be administered frequently or prior to injury because they lose their in vivo activity rapidly either by lymphatic clearance, or oxidation-mediated deactivation. In this study, we have encapsulated RvD1 in liposomes and established its efficacy in the mouse model of ObOA at much lower dosages than freely administered RvD1. Liposomal RvD1 (lipo-RvD1) acted as a source of the RvD1 molecules for ~11 days in vitro in synovial fluid derived from patients. When administered prophylactically or therapeutically, lipo-RvD1 suppressed cartilage damage in male C57BL/6 mice compared to untreated and free RvD1 treatments. This efficacy was achieved by increasing the proportion of the proresolution M2 macrophages over proinflammatory M1 macrophages in the synovial membrane. These results show the potential of lipo-RvD1 as an anti-OA agent.

show abstract

Resolvin D1 reduces inflammation in co-cultures of primary human macrophages and adipocytes by triggering macrophages

Cited by 11 publications

References 54 publications

Modeling human heterogeneity of obesity with diversity outbred mice reveals a fat mass‐dependent therapeutic window for resolvin E1

Modeling human heterogeneity of obesity with diversity outbred mice reveals a fat mass‐dependent therapeutic window for resolvin E1

Sustained release resolvin D1 liposomes are effective in the treatment of osteoarthritis in obese mice

Sustained release Resolvin D1 liposomes are effective in the treatment of osteoarthritis in obese mice

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