n‐3 polyunsaturated fatty acids provoke a specific transcriptional profile in rabbit adipose‐derived stem cells in vitro

Vackova, Eкaterina; Bosnakovski, Darko; Bjørndal, Bodil; Yonkova, P.; Grigorova, N.; Ivanova, Zh.; Penchev, G.; Simeonova, G.; Miteva, Lyuba; Milanova, Aneliya; Vachkova, E.; Stanilova, Spaska; Georgiev, Ivan

doi:10.1111/jpn.13075

Cited by 4 publications

(6 citation statements)

References 45 publications

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“…However, new potential treatment options are available, such as the transplantation of autologous ASCs [ 101 ]. In addition, in rabbit visceral ASCs in vitro, the activation of additional lipolysis pathways has been observed compared to a subcutaneous group, where EPA up-regulates the mRNA expression of lipolysis-associated genes to a greater extent than DHA [ 102 ]. Regarding the PUFAs, it has been reported that combined EPA-DHA treatment negatively affects leptin and obesity-related membrane-type MT1-MMP (MMP-14) mRNA expression in rabbit subcutaneous ASCs in vitro [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Outlook of Adipose-Derived Stem Cells: Challenges to Their Clinical Application in Horses

Petrova

Vachkova

2023

Veterinary Sciences

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Adipose tissue is recognized as the major endocrine organ, potentially acting as a source of mesenchymal stem cells for various applications in regenerative medicine. Athletic horses are often exposed to traumatic injuries, resulting in severe financial losses. The development of adipose-derived stem cells’ regenerative potential depends on many factors. The extraction of stem cells from subcutaneous adipose tissue is non-invasive, non-traumatic, cheaper, and safer than other sources. Since there is a lack of unique standards for identification, the isolated cells and applied differentiation protocols are often not species-specific; therefore, the cells cannot reveal their multipotent properties, so their stemness features remain questionable. The current review discusses some aspects of the specificity of equine adipose stem cells concerning their features, immunophenotyping, secretome profile, differentiation abilities, culturing conditions, and consequent possibilities for clinical application in concrete disorders. The presented new approaches elucidate the possibility of the transition from cell-based to cell-free therapy with regenerative purposes in horses as an alternative treatment to cellular therapy. In conclusion, their clinical benefits should not be underestimated due to the higher yield and the physiological properties of adipose-derived stem cells that facilitate the healing and tissue regeneration process and the ability to amplify the effects of traditional treatments. More profound studies are necessary to apply these innovative approaches when treating traumatic disorders in racing horses.

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Section: Discussionmentioning

confidence: 99%

Outlook of Adipose-Derived Stem Cells: Challenges to Their Clinical Application in Horses

Petrova

Vachkova

2023

Veterinary Sciences

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“…Some authors have proposed that DHA supplementation exerts an anti-obesity effect by promoting lipolysis and upregulating essential lipolytic genes, such as adipose triglyceride lipase, hormone-sensitive lipase, and monoacylglycerol lipase [23,27,36]. Others claim that alleviated intracellular lipid accumulation upon DHA supplementation is mainly based on increased mitochondrial β-oxidation in adipose tissue [22,38].…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, DHA, despite being a member of the PUFA family, often provokes lipolytic and antiadipogenic effects, along with enhanced mitochondrial biogenesis. This further results in a noteworthy level of weight reduction and suppressed adipocyte proliferation, with many studies even reporting apoptotic effects [22][23][24][25][26][27]. However, in obese individuals, these outcomes may lead to lipotoxicity and trigger adverse health consequences [28,29].…”

Section: Introductionmentioning

confidence: 99%

DHA-Provoked Reduction in Adipogenesis and Glucose Uptake Could Be Mediated by Gps2 Upregulation in Immature 3T3-L1 Cells

Grigorova,

Ivanova,

Vachkova

et al. 2023

IJMS

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The signaling pathway of fatty acids in the context of obesity is an extensively explored topic, yet their primary mechanism of action remains incompletely understood. This study aims to examine the effect of docosahexaenoic acid (DHA) on some crucial aspects of adipogenesis in differentiating 3T3-L1 cells, using palmitic acid-treated (PA), standard differentiated, and undifferentiated adipocytes as controls. Employing 60 µM DHA or PA, 3T3-L1 preadipocytes were treated from the onset of adipogenesis, with negative and positive controls included. After eight days, we performed microscopic observations, cell viability assays, the determination of adiponectin concentration, intracellular lipid accumulation, and gene expression analysis. Our findings demonstrated that DHA inhibits adipogenesis, lipolysis, and glucose uptake by suppressing peroxisome proliferator-activated receptor gamma (Pparg) and G-protein coupled receptor 120 (Gpr120) gene expression. Cell cytotoxicity was ruled out as a causative factor, and β-oxidation involvement was suspected. These results challenge the conventional belief that omega-3 fatty acids, acting as Pparg and Gpr120 agonists, promote adipogenesis and enhance insulin-dependent glucose cell flux. Moreover, we propose a novel hypothesis suggesting the key role of the co-repressor G protein pathway suppressor 2 in mediating this process. Additional investigations are required to elucidate the molecular mechanisms driving DHA’s anti-adipogenic effect and its broader health implications.

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“…Adipocyte lipolysis is activated, and free fatty acid delivery from adipose tissue to the liver is continuously provoked. Besides, several in vitro and in vivo experiments have demonstrated that PUFAs stimulate lipolysis in adipose tissue (Rydén & Arner, 2017; Sehl et al, 2019; Vackova et al, 2019). Therefore, the combination of severe diet restriction with KO or FO, used in our experiment, probably promotes overstimulation of lipolysis in fat depots, resulting in excessive release of free fatty acids.…”

Section: Discussionmentioning

confidence: 99%

“…In turn, this leads to the development of insulin resistance, cardiovascular, endocrine and metabolic diseases (Bassey et al, 2018;Hutchison et al, 2019;Nikhra, 2018;Weickert, 2012). The age-related reproductive hormonal decline further complicates these daily overweightpredisposing factors, promoting metabolic deceleration and central adiposity with all its fallouts (Nikhra, 2018;Sitzmann et al, 2008Sitzmann et al, , 2014Urbanski & Sorwell, 2012).…”

Section: Introductionmentioning

confidence: 99%

Diet restriction alone improves glucose tolerance and insulin sensitivity than its coadministration with krill or fish oil in a rabbit model of castration‐induced obesity

Grigorova

Ivanova

Bjørndal

et al. 2022

Animal Physiology Nutrition

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This study investigated the effect of 50% diet restriction and its coadministration with krill oil (KO) or fish oil (FO) on glucose tolerance and insulin sensitivity in a rabbit model of obesity. Castrated male rabbits were 50% restricted fed and supplemented with KO or FO (600 mg omega‐3 polyunsaturated fatty acids/daily) for 2 months. Simultaneously, two control groups were used: castrated, full‐diet‐fed and castrated, 50% restricted fed rabbits without additives restricted group (RG). The energy‐restricted diet decreased final body weight in castrated male rabbits and improved most insulin sensitivity and β‐cell function indexes. Combining the same diet and KO or FO, further reduced fasting blood glucose levels. However, this feed regime significantly accelerated insulin secretion and reduced gene expression of insulin receptor substrate‐1, pyruvate kinase and 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2. This was manifested by reduced dynamic insulin sensitivity, assessment homoeostasis‐β‐cell function indices and increased glucose elimination rate to levels comparable to or above the obese animals. Aspartate and alanine aminotransferases enzyme activities were raised more than those in the obese group. Surprisingly, KO and FO administration downregulated acetyl‐coenzyme A oxidase and carnitine palmitoyltransferase 2 messenger RNA gene expression compared to the RG. In conclusion, we can assume that a better effect on insulin sensitivity and glucose tolerance was observed in the diet restriction alone than in the coadministration of KO or FO when animals are exposed to highly obesity predisposing factors. These effects could be at least in part ascribed to the modified gene expression levels of some critical enzymes and factors involved in liver glucose metabolism and β‐oxidation.

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n‐3 polyunsaturated fatty acids provoke a specific transcriptional profile in rabbit adipose‐derived stem cells in vitro

Cited by 4 publications

References 45 publications

Outlook of Adipose-Derived Stem Cells: Challenges to Their Clinical Application in Horses

Outlook of Adipose-Derived Stem Cells: Challenges to Their Clinical Application in Horses

DHA-Provoked Reduction in Adipogenesis and Glucose Uptake Could Be Mediated by Gps2 Upregulation in Immature 3T3-L1 Cells

Diet restriction alone improves glucose tolerance and insulin sensitivity than its coadministration with krill or fish oil in a rabbit model of castration‐induced obesity

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