Lipid ratios representing SCD1, FADS1, and FADS2 activities as candidate biomarkers of early growth and adiposity

Olga, Laurentya; Diepen, Janna A. van; Bobeldijk-Pastorova, Ivana; Gross, Gabriele; Prentice, Philippa; Snowden, Stuart G.; Furse, Samuel; Kooistra, Teake; Hughes, Ieuan A.; Schoemaker, Marieke H.; Tol, Eric A.F. van; Duyvenvoorde, Wim van; Wielinga, Peter Y.; Ong, Ken K.; Dunger, David; Kleemann, Robert; Koulman, Albert

doi:10.1016/j.ebiom.2020.103198

Cited by 11 publications

(17 citation statements)

References 38 publications

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“…It is likely that inflammation-resolving oxylipins were formed from their precursor fatty acids present in KrO (EPA and DHA), but these precursors themselves can also be enzymatically synthesized from ALA. The enzymes responsible for omega-3 PUFA processing are the same as those for omega-6 processing but the rate-limiting enzyme, delta-6-desaturase, has a higher preference for omega-3 FAs relative to omega-6 FAs [ 49 , 50 ]. Thus, an enhanced conversion of ALA in the presence of KrO may also explain the pronounced increases in anti-inflammatory oxylipins.…”

Section: Discussionmentioning

confidence: 99%

Krill Oil Treatment Increases Distinct PUFAs and Oxylipins in Adipose Tissue and Liver and Attenuates Obesity-Associated Inflammation via Direct and Indirect Mechanisms

et al. 2021

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The development of obesity is characterized by the metabolic overload of tissues and subsequent organ inflammation. The health effects of krill oil (KrO) on obesity-associated inflammation remain largely elusive, because long-term treatments with KrO have not been performed to date. Therefore, we examined the putative health effects of 28 weeks of 3% (w/w) KrO supplementation to an obesogenic diet (HFD) with fat derived mostly from lard. The HFD with KrO was compared to an HFD control group to evaluate the effects on fatty acid composition and associated inflammation in epididymal white adipose tissue (eWAT) and the liver during obesity development. KrO treatment increased the concentrations of EPA and DHA and associated oxylipins, including 18-HEPE, RvE2 and 14-HDHA in eWAT and the liver. Simultaneously, KrO decreased arachidonic acid concentrations and arachidonic-acid-derived oxylipins (e.g., HETEs, PGD2, PGE2, PGF2α, TXB2). In eWAT, KrO activated regulators of adipogenesis (e.g., PPARγ, CEBPα, KLF15, STAT5A), induced a shift towards smaller adipocytes and increased the total adipocyte numbers indicative for hyperplasia. KrO reduced crown-like structures in eWAT, and suppressed HFD-stimulated inflammatory pathways including TNFα and CCL2/MCP-1 signaling. The observed eWAT changes were accompanied by reduced plasma leptin and increased plasma adiponectin levels over time, and improved insulin resistance (HOMA-IR). In the liver, KrO suppressed inflammatory signaling pathways, including those controlled by IL-1β and M-CSF, without affecting liver histology. Furthermore, KrO deactivated hepatic REL-A/p65-NF-κB signaling, consistent with increased PPARα protein expression and a trend towards an increase in IkBα. In conclusion, long-term KrO treatment increased several anti-inflammatory PUFAs and oxylipins in WAT and the liver. These changes were accompanied by beneficial effects on general metabolism and inflammatory tone at the tissue level. The stimulation of adipogenesis by KrO allows for safe fat storage and may, together with more direct PPAR-mediated anti-inflammatory mechanisms, attenuate inflammation.

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Section: Discussionmentioning

confidence: 99%

Krill Oil Treatment Increases Distinct PUFAs and Oxylipins in Adipose Tissue and Liver and Attenuates Obesity-Associated Inflammation via Direct and Indirect Mechanisms

et al. 2021

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“…The process by which PUFA are synthesized from LA and ALA in the human body involves Δ6 desaturase (D6D, LA to γ-linolenic acid, ALA to stearidonic acid) and Δ5 desaturase [D5D, dihomo-γ-linolenic acid (DGLA) to arachidonic acid (AA), eicosatetraene acid to eicosapentaenoic acid (EPA)]. Product-to-precursor ratios have been used to represent enzyme indices ( 26 – 28 ). In this study, the D6D index was estimated by DGLA (20:3n-6)/LA (18:2n-6), the D5D index was estimated by AA (20:4n-6)/DGLA (20:3n-6), and the ratio for estimation of the elongase activity was C18:1/C16:1 ( 29 ).…”

Section: Methodsmentioning

confidence: 99%

Association of Prepregnancy Obesity and Remodeled Maternal-Fetal Plasma Fatty Acid Profiles

Chen

et al. 2022

Front. Nutr.

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BackgroundFatty acids, especially polyunsaturated fatty acid (PUFA), are found abundantly in the brain and are fundamental for a fetus's growth. The fatty acid profiles of mothers and fetuses may be affected by maternal prepregnancy body mass index (pre-BMI), thus affecting fetal growth and development.MethodsA total of 103 mother-fetus pairs were divided into overweight/obese (OW, n = 26), normal weight (NW, n = 60), and underweight (UW, n = 17) groups according to pre-BMI. Fatty acid profiles in maternal and umbilical cord plasma were analyzed by gas chromatography.ResultsThe infant birth BMI z-score of the OW group was higher than that of the NW and UW groups (p < 0.05). The OW mothers had significantly higher plasma n-6 PUFA and n-6/n-3, but lower docosahexaenoic acid (DHA) and n-3 PUFA (p < 0.05). In cord plasma, the proportions of DHA and n-3 PUFA were lower in the OW group (p < 0.05), whereas the n-6/n-3 ratio was higher in the OW group (p < 0.05). The pre-BMI was negatively correlated with cord plasma DHA in all subjects (r = −0.303, p = 0.002), and the same negative correlation can be observed in the OW group (r = −0.561, p = 0.004), but not in the NW and UW groups (p > 0.05). The pre-BMI was positively correlated with cord plasma n-6/n-3 in all subjects (r = 0.325, p = 0.001), and the same positive correlation can be found in the OW group (r = 0.558, p = 0.004), but not in NW and UW groups (p > 0.05).ConclusionsMaternal pre-BMI was associated with the maternal-fetal plasma fatty acid profiles, whereas the adverse fatty acid profiles are more noticeable in the prepregnancy OW mothers.

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“…Of note, species differences should be still considered carefully, especially regarding the activity and allosteric regulation of the enzymes involved. The lipid moieties, however, are still comparable and the conversion of omega-3, omega-6 and omega-9 fatty acids depicted in the desaturase framework in Figure 3 ( Olga et al., 2021 ) apply to both human and mouse fatty acids. Note: Since the fatty acid conversions that are enzymatically catalyzed by desaturases ( Figure 3 ) occur in both humans and mice, ratio of the fatty acid used as substrate (educt) and the resulting fatty acid product that is formed provides a measure for desaturase activity (i.e., desaturase activity index).…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…This protocol represents a reliable and versatile approach to translate and validate candidate lipid biomarkers from animal models to a human cohort. For complete details on the use and execution of this protocol, please refer to Olga et al. (2021) .…”

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confidence: 99%

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Lipid profiling analyses from mouse models and human infants

Olga¹,

Bobeldijk-Pastorova²,

Bas³

et al. 2022

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Lipid ratios representing SCD1, FADS1, and FADS2 activities as candidate biomarkers of early growth and adiposity

Cited by 11 publications

References 38 publications

Krill Oil Treatment Increases Distinct PUFAs and Oxylipins in Adipose Tissue and Liver and Attenuates Obesity-Associated Inflammation via Direct and Indirect Mechanisms

Krill Oil Treatment Increases Distinct PUFAs and Oxylipins in Adipose Tissue and Liver and Attenuates Obesity-Associated Inflammation via Direct and Indirect Mechanisms

Association of Prepregnancy Obesity and Remodeled Maternal-Fetal Plasma Fatty Acid Profiles

Lipid profiling analyses from mouse models and human infants

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