Modification of subcutaneous white adipose tissue inflammation by omega-3 fatty acids is limited in human obesity-a double blind, randomised clinical trial

Fisk, Helena L.; Childs, Caroline E.; Miles, Elizabeth A.; Ayres, R. C. S.; Noakes, Paul S.; Paras-Chavez, Carolina; Kuda, Ondřej; Kopecký, Jan; Antoun, Elie; Lillycrop, Karen A.; Calder, Philip C.

doi:10.1016/j.ebiom.2022.103909

Cited by 31 publications

(35 citation statements)

References 64 publications

(69 reference statements)

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“…So far, studies regarding inflammation in overweight and obese subjects have mostly explored circulation markers of inflammation, although it is well known that PUFAs present in adipose tissue is the precursors for lipid mediators that are involved in inflammation onset [ 53 , 60 ]. Recently, Fisk et al [ 61 ] revealed that greater subcutaneous adipose tissue inflammation in obesity is associated with lower levels of specialized pro-resolving mediators and hydroxyl-DHA metabolites together with altered expression of genes involved in n−3 PUFAs activation, oxylipin synthesis, inflammation, and immune response in adipose tissue. Moreover, dietary treatment with fish oil in the study of Fisk et al [ 61 ] did not induce increased generation of the EPA and DHA metabolites in overweight/obese subjects to the same extent as normal weight individuals.…”

Section: Metabolic Conversion Of Polyunsaturated Fatty Acids and Thei...mentioning

confidence: 99%

“…Recently, Fisk et al [ 61 ] revealed that greater subcutaneous adipose tissue inflammation in obesity is associated with lower levels of specialized pro-resolving mediators and hydroxyl-DHA metabolites together with altered expression of genes involved in n−3 PUFAs activation, oxylipin synthesis, inflammation, and immune response in adipose tissue. Moreover, dietary treatment with fish oil in the study of Fisk et al [ 61 ] did not induce increased generation of the EPA and DHA metabolites in overweight/obese subjects to the same extent as normal weight individuals. The authors concluded (Fisk 2022) that, based on adipose tissue status, there may be a need for personalized LC n−3 PUFA supplementation in obesity.…”

Section: Metabolic Conversion Of Polyunsaturated Fatty Acids and Thei...mentioning

confidence: 99%

“…The authors concluded (Fisk 2022) that, based on adipose tissue status, there may be a need for personalized LC n−3 PUFA supplementation in obesity. Furthermore, the results of the study of Fisk et al [ 61 ] emphasize the importance of adipose tissue PUFA status in terms of manifestation of obesity-induced inflammation.…”

Section: Metabolic Conversion Of Polyunsaturated Fatty Acids and Thei...mentioning

confidence: 99%

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Effects of Dietary α-Linolenic Acid Treatment and the Efficiency of Its Conversion to Eicosapentaenoic and Docosahexaenoic Acids in Obesity and Related Diseases

et al. 2022

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The essential fatty acid alpha-linolenic acid (ALA) is present in high amounts in oils such as flaxseed, soy, hemp, rapeseed, chia, and perilla, while stearidonic acid is abundant in echium oil. ALA is metabolized to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by desaturases and elongases in humans. The conversion of ALA to EPA and DHA is limited, and these long-chain n−3 polyunsaturated fatty acids (PUFAs) are mainly provided from dietary sources (fish and seafood). This review provides an overview of studies that explored the effects of dietary supplementation with ALA in obesity and related diseases. The obesity-associated changes of desaturase and elongase activities are summarized, as they could influence the metabolic conversion of ALA. Generally, supplementation with ALA or ALA-rich oils leads to an increase in EPA levels and has no effect on DHA or omega-3 index. According to the literature data, stearidonic acid could enhance conversion of ALA to long-chain n−3 PUFA in obesity. Recent studies confirm that EPA and DHA intake should be considered as a primary dietary treatment strategy for improving the omega-3 index in obesity and related diseases.

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Section: Metabolic Conversion Of Polyunsaturated Fatty Acids and Thei...mentioning

confidence: 99%

Section: Metabolic Conversion Of Polyunsaturated Fatty Acids and Thei...mentioning

confidence: 99%

Section: Metabolic Conversion Of Polyunsaturated Fatty Acids and Thei...mentioning

confidence: 99%

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Effects of Dietary α-Linolenic Acid Treatment and the Efficiency of Its Conversion to Eicosapentaenoic and Docosahexaenoic Acids in Obesity and Related Diseases

et al. 2022

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“…In addition to potentially influencing inflammatory mediator signalling, EPA and DHA elicit their actions via altering the activity of transcription factors to modulate inflammation and other processes in WAT ( 28 , 29 ). We previously reported the modulation of the scWAT transcriptome in human obesity by EPA and DHA resulting in downregulation of genes involved in immune and inflammatory responses ( 30 ). Furthermore, EPA and DHA have been reported to regulate the expression of genes associated with lipid accumulation in WAT ( 31 , 32 ), decrease hepatic fibrosis accompanying metabolic complication through decreasing expression of collagen-associated genes and the presence of collagen fibres ( 33 , 34 ), and impair collagen reorganisation in wound healing in mice ( 35 ).…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of Subcutaneous White Adipose Tissue Inflammatory Environment Modelling in Non-Insulin Resistant Obesity and Responses to Omega-3 Fatty Acids – A Double Blind, Randomised Clinical Trial

et al. 2022

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BackgroundObesity is associated with enhanced lipid accumulation and the expansion of adipose tissue accompanied by hypoxia and inflammatory signalling. Investigation in human subcutaneous white adipose tissue (scWAT) in people living with obesity in which metabolic complications such as insulin resistance are yet to manifest is limited, and the mechanisms by which these processes are dysregulated are not well elucidated. Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have been shown to modulate the expression of genes associated with lipid accumulation and collagen deposition and reduce the number of inflammatory macrophages in adipose tissue from individuals with insulin resistance. Therefore, these lipids may have positive actions on obesity associated scWAT hypertrophy and inflammation.MethodsTo evaluate obesity-associated tissue remodelling and responses to LC n-3 PUFAs, abdominal scWAT biopsies were collected from normal weight individuals and those living with obesity prior to and following 12-week intervention with marine LC n-3 PUFAs (1.1 g EPA + 0.8 g DHA daily). RNA sequencing, qRT-PCR, and histochemical staining were used to assess remodelling- and inflammatory-associated gene expression, tissue morphology and macrophage infiltration.ResultsObesity was associated with scWAT hypertrophy (P < 0.001), hypoxia, remodelling, and inflammatory macrophage infiltration (P = 0.023). Furthermore, we highlight the novel dysregulation of Wnt signalling in scWAT in non-insulin resistant obesity. LC n-3 PUFAs beneficially modulated the scWAT environment through downregulating the expression of genes associated with inflammatory and remodelling pathways (P <0.001), but there were altered outcomes in individuals living with obesity in comparison to normal weight individuals.ConclusionOur data identify dysregulation of Wnt signalling, hypoxia, and hypertrophy, and enhanced macrophage infiltration in scWAT in non-insulin resistant obesity. LC n-3 PUFAs modulate some of these processes, especially in normal weight individuals which may be preventative and limit the development of restrictive and inflammatory scWAT in the development of obesity. We conclude that a higher dose or longer duration of LC n-3 PUFA intervention may be needed to reduce obesity-associated scWAT inflammation and promote tissue homeostasis.Clinical Trial Registrationwww.isrctn.com, identifier ISRCTN96712688.

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“…Earlier studies reported that omega-3 fatty acids (EPA+DHA) could decrease macrophage numbers, crown-like structures and expression of some inflammatory genes in human subcutaneous adipose tissue [24,25] and could increase concentrations of pro-resolving lipid mediators mainly in visceral adipose tissue [25]. A more recent study reported that omega-3 fatty acids could alter endocannabinoid and other lipid mediator concentrations ad gene expression in human subcutaneous adipose tissue but that adipose tissue from those living with obesity showed less profonde changes than that from healthy weight individuals [26,27]. This study has raised questions about better targeting of adipose tissue in those living with obesity.…”

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confidence: 99%

Dietary factors and low-grade inflammation in relation to overweight and obesity revisted

Calder

2022

Br J Nutr

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Modification of subcutaneous white adipose tissue inflammation by omega-3 fatty acids is limited in human obesity-a double blind, randomised clinical trial

Cited by 31 publications

References 64 publications

Effects of Dietary α-Linolenic Acid Treatment and the Efficiency of Its Conversion to Eicosapentaenoic and Docosahexaenoic Acids in Obesity and Related Diseases

Effects of Dietary α-Linolenic Acid Treatment and the Efficiency of Its Conversion to Eicosapentaenoic and Docosahexaenoic Acids in Obesity and Related Diseases

Dysregulation of Subcutaneous White Adipose Tissue Inflammatory Environment Modelling in Non-Insulin Resistant Obesity and Responses to Omega-3 Fatty Acids – A Double Blind, Randomised Clinical Trial

Dietary factors and low-grade inflammation in relation to overweight and obesity revisted

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