Effects of In Vitro Muscle Contraction on Thermogenic Protein Levels in Co-Cultured Adipocytes

Nintou, Eleni; Karligiotou, Eleni; Vliora, Maria; Fatouros, Ioannis G.; Jamurtas, Athanasios Z.; Sakellaridis, Nikos; Dimas, Konstantinos; Flouris, Andreas D.

doi:10.3390/life11111227

Cited by 7 publications

(6 citation statements)

References 59 publications

(82 reference statements)

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“…The expression of UCP-1, a thermogenic gene, in brown adipocytes is an essential prerequisite for promoting energy consumption in beige adipocytes. Brown and beige adipocytes expressing UCP-1 play an important role in metabolic activity [ 8 , 28 ]; therefore, it is necessary to verify Cu B, Cu E, and Cu I, which increase the number of brown and beige adipocytes. RT-qPCR and Western blotting analyses were performed to measure the increase in the expression of UCP-1, which plays an important role in the change from white adipocytes to brown adipocytes, such as an increase in energy consumption efficiency.…”

Section: Resultsmentioning

confidence: 99%

Cucurbitacin B-, E-, and I-Induced Browning of White Adipocytes Is Promoted by the Inhibition of Phospholipase D2

Park

Kang

et al. 2022

IJMS

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The mechanism of white adipose tissue browning is not well understood; however, naturally occurring compounds are known to play a positive role. The effects of cucurbitacins B, E, and I on the browning of mature white adipocytes were investigated. First, the cell viability exhibited by cucurbitacins B, E, and I in pre- and mature adipocytes was verified. Cucurbitacins B, E, and I had no effect on cell viability in pre- and mature adipocytes at concentrations up to 300 nM. To investigate the characteristics of representative beige adipocytes, the formation and morphology of cucurbitacin B, E, and I lipid droplets were verified. The total lipid droplet surface area, maximum Feret diameter, and total Nile red staining intensity of cucurbitacin B-, E-, and I-treated adipocytes were lower than those of mature white adipocytes. Furthermore, treatment of white mature adipocytes with cucurbitacin B, E, and I led to the formation of several small lipid droplets that are readily available for energy expenditure. We evaluated the effect of cucurbitacins B, E, and I on the expression of representative browning markers UCP1, PGC1a, and PRDM16, which participate in the browning of white adipose tissue. Cucurbitacins B, E, and I increased the mRNA and protein expression levels of UCP1, PGC1a, and PRDM16 in a concentration-dependent manner. To promote energy consumption by beige adipocytes, active mitochondrial biogenesis is essential. Next, we investigated the effects of cucurbitacin B, E, and I on mitochondrial biogenesis in mature adipocytes. Mitochondrial mass increased when mature adipocytes were treated with cucurbitacin B, E, and I. The degree of cucurbitacin B-, E- and I-induced transformation of white adipocytes into beige adipocytes was in the order of Cu E > Cu B > Cu I. To verify the effect of phospholipase D2 on the browning of white adipocytes, CAY10594—a PLD2 pharmacological inhibitor, and a knockdown system were used. PLD2 inhibition and knockdown improved the expression levels of UCP1, PGC1a, and PRDM16. In addition, PLD2 inhibition and knockdown in mature white adipocytes promoted mitochondrial biosynthesis. The effect of PLD2 inhibition and knockdown on promoting browning of white adipocytes significantly increased when Cu B, Cu E, and Cu I were co-treated. These data indicate that mature white adipocytes’ beige properties were induced by cucurbitacins B, E, and I. These effects became more potent by the inhibition of PLD2. These findings provide a model for determining anti-obesity agents that induce browning and increase energy expenditure in mature white adipocytes.

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Section: Resultsmentioning

confidence: 99%

Cucurbitacin B-, E-, and I-Induced Browning of White Adipocytes Is Promoted by the Inhibition of Phospholipase D2

Park

Kang

et al. 2022

IJMS

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“…Here we examined the effects of irisin on adipocytes, but if the present results are also confirmed in muscle cells, this would suggest that irisin acts as an autocrine agent to induce fatigue, potentially as a protective mechanism. Also, it would be promising to use a systemic or an in vitro co-culture approach to understand the cross-talk between the muscle and adipose tissues and its potential role on fatigue development [31].…”

Section: Discussionmentioning

confidence: 99%

Irisin regulates thermogenesis and lipolysis in 3T3-L1 adipocytes

Vliora

Grillo

Corsini

et al. 2022

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…This could be because EPS cannot represent the systemic effect of in vivo exercise. Studies involving organ-to-muscle communication by co-culturing muscle cells with other cell types 55 and using EPS-conditioned medium [56][57][58] have been conducted to address these differences. Although our findings demonstrated that EPS mimics in vivo exercise transcriptionally, it does not represent the metabolic aspect of in vivo exercise.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of a cellular exercise model based on electrical pulse stimulation

Lee

Kim

Shin

et al. 2022

Sci Rep

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Skeletal muscle communicates with other organs via myokines, which are secreted by muscle during exercise and exert various effects. Despite much investigation of the exercise, the underlying molecular mechanisms are still not fully understood. Here, we applied an in vitro exercise model in which cultured C2C12 myotubes were subjected to electrical pulse stimulation (EPS), which mimics contracting muscle. Based on the significantly up- and down-regulated genes in EPS, we constructed an in silico model to predict exercise responses at the transcriptional level. The in silico model revealed similarities in the transcriptomes of the EPS and exercised animals. Comparative analysis of the EPS data and exercised mouse muscle identified putative biomarkers in exercise signaling pathways and enabled to discover novel exercise-induced myokines. Biochemical analysis of selected exercise signature genes in muscle from exercised mice showed that EPS mimics in vivo exercise, at least in part, at the transcriptional level. Consequently, we provide a novel myokine, Amphiregulin (AREG), up-regulated both in vitro and in vivo, that would be a potential target for exercise mimetics.

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Effects of In Vitro Muscle Contraction on Thermogenic Protein Levels in Co-Cultured Adipocytes

Cited by 7 publications

References 59 publications

Cucurbitacin B-, E-, and I-Induced Browning of White Adipocytes Is Promoted by the Inhibition of Phospholipase D2

Cucurbitacin B-, E-, and I-Induced Browning of White Adipocytes Is Promoted by the Inhibition of Phospholipase D2

Irisin regulates thermogenesis and lipolysis in 3T3-L1 adipocytes

Genome-wide analysis of a cellular exercise model based on electrical pulse stimulation

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