FADS2 genotype regulates delta-6 desaturase activity and inflammation in human adipose tissue

Vaittinen, Maija; Walle, Paula; Kuosmanen, Emmi; Männistö, Ville; Käkelä, Pirjo; Ågren, Jyrki; Schwab, Ursula; Pihlajamäki, Jussi

doi:10.1194/jlr.m059113

Cited by 50 publications

(41 citation statements)

References 34 publications

(37 reference statements)

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“…The higher plasma n-6/n-3 ratio is indicative of increased adipocyte proliferation and differentiation, lipogenesis and PPARγ signaling [49], as well as a more pro-inflammatory state. As eicosanoid levels derived from the n-3 and n-6 series are controlled by the rate-limiting steps catalyzed by D5D and D6D [50], the higher D6D index was also consistent with a pre-diabetic state because this activity correlates directly with diabetes risk and insulin resistance (whereas D5D activity has a reciprocal correlation; [51]) and with inflammatory marker IL-1β in both visceral and subcutaneous fat [23]. If this scenario is correct, the proteomics of non-visceral fat depots align more closely to the plasma FFA profile.…”

Section: Discussionmentioning

confidence: 95%

Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes

Hung

Bronec

Napoli

et al. 2018

Biochemical Journal

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Ileal interposition (IT) surgery delays the onset of diabetes in a rat model of type-2 diabetes (UCD-T2DM). Here, to gain a deeper understanding of the molecular events underlying the effects of IT surgery, we examined the changes in the proteome of four white adipose depots (retroperitoneal, mesenteric, inguinal, and epididymal) and plasma-free fatty acid profile in pre-diabetic rats 1.5 months following IT or sham surgery. The IT-mediated changes were exerted mainly in mesenteric fat and spanned from delayed adipocyte maturation to a neuroendocrine remodeling. Conversely, inguinal, retroperitoneal, and epididymal depots showed opposite trends consistent with increased adipocyte maturation and adipogenesis development prior to overt signs of diabetes, probably orchestrated by peroxisome proliferator-activated receptor gamma signaling and higher plasma -6/-3 free fatty acid ratios. The resulting scenario suggests a targeted use of surgical strategies that seek to delay or improve diabetes in order to manipulate adipose depot-specific responses to maximize the duration and beneficial effects of the surgery.

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Section: Discussionmentioning

confidence: 95%

Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes

Hung

Bronec

Napoli

et al. 2018

Biochemical Journal

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“…It is the rate-limiting metabolic enzyme in the conversions of linoleic acid into arachidonic acid (AA) and of α-linolenic acid into eicosapentanoic acid (EPA) (Park et al 2015). Both AA and EPA are involved in the inflammatory response (Vaittinen et al 2016). FADS2 activity is known to be increased in breast cancer; therefore, its inhibition is a potential treatment method (Lane et al 2003;Pender-Cudlip et al 2013).…”

Section: Resultsmentioning

confidence: 99%

3′ UTR G-quadruplexes regulate miRNA binding

Rouleau

Glouzon

Brumwell

et al. 2017

RNA

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MicroRNAs (miRNAs) are small noncoding RNAs that repress the translation of their target genes. It has previously been shown that a target's availability to miRNA can be affected by its structure. G-quadruplexes (G4) are noncanonical structures adopted by G-rich nucleic acids that have been shown to have multiple biological functions. In this study, whether or not G4 structures' presence in the 3' UTRs of mRNAs can hinder miRNA binding was investigated. Putative G4 overlapping with predicted miRNAs' binding sites was searched for, and 44,294 hits were found in humans. The FADS2 mRNA/mir331-3p pair was selected as a model example. In-line probing and G4-specific fluorescent ligand experiments binding were performed and confirmed the presence of a G4 near the predicted miRNA binding site. Subsequent luciferase assays showed that the presence of the G4 prevents the binding of mir331-3p in cellulo. Together, these results served as proof of concept that a G4 structure present in a 3' UTR sequence should be taken into consideration when predicting miRNA binding sites.

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“…FADS2 plays a pivotal role in the biosynthesis of polyunsaturated fatty acids [29][30][31][32]. Genome-wide association studies (GWAS) have confirmed the effects of FADS2 genetic variations on diseases related to lipid metabolism [33,34].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in Fatty Acid Desaturase 2 Gene Are Associated with Milk Production Traits in Chinese Holstein Cows

Gao

Wang

et al. 2020

Animals

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This study investigated the single nucleotide polymorphisms (SNPs) of Fatty acid desaturase 2 (FADS2) gene and further explored their genetic effects on conventionally collected milk production traits in Chinese Holstein cows using 18,264 test-day records of 841 cows. One missense mutation c. 908 C > T (SNP site in the complementary DNA sequence), which caused an amino acid change from alanine to valine (294Ala > Val), and two 3’ untranslated region (UTR) SNPs, c.1571 G > A and c.2776 A > G were finally identified. The SNP c.908 C > T was significantly associated with test-day milk yield, fat percentage and 305-day milk, fat and protein yield. In particular, the T allele of the SNP c.908 C > T showed a significant association with decreased somatic cell score (SCS) in the investigated population. Significant relationship between the SNP c.1571 G > A and 305-day milk yield showed that genotype GG was linked to the highest milk yield. Substituting the allele G for A at the c.2776 A > G locus resulted in a decrease of protein percentage. Our results demonstrated that FADS2 was an interesting candidate for selection to increase milk production and improve resistance against mastitis.

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FADS2 genotype regulates delta-6 desaturase activity and inflammation in human adipose tissue

Cited by 50 publications

References 34 publications

Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes

Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes

3′ UTR G-quadruplexes regulate miRNA binding

Polymorphisms in Fatty Acid Desaturase 2 Gene Are Associated with Milk Production Traits in Chinese Holstein Cows

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