scholarly journals Leptin Rapidly Induces the Expression of Metabolic and Myokine Genes in C2C12 Muscle Cells to Regulate Nutrient Partition and Oxidation

2015 ◽  
Vol 35 (1) ◽  
pp. 92-103 ◽  
Author(s):  
Yuriy Nozhenko ◽  
Ana M. Rodríguez ◽  
Andreu Palou
Keyword(s):  
Time Course ◽  
Leptin Receptor ◽  
Uncoupling Protein ◽  
Muscle Cells ◽  
Pyruvate Dehydrogenase Kinase ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels

Background: Skeletal muscle can experience pronounced metabolic adaptations in response to extrinsic stimuli, and expresses leptin receptor (OB-Rb). We aimed to further the understanding of leptin effects on muscle cells, by studying the expression of key energy metabolism genes in C2C12 myotubes. Methods: We performed a dose-time-dependent study with physiological concentrations of leptin: 5, 10 and 50ng/ml, for 0, 30', 3h, 6h, 12h and 24h, also monitoring time-course changes in non-treated cells. mRNA levels were analyzed by RT-qPCR and peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) protein levels by western blot. Results: The most significant effects were observed with 50ng/ml leptin. In the short-term (30' and/or 3h), leptin significantly induced the expression of PGC1α, muscle carnitine palmitoyl transferase 1 (mCPT1), uncoupling protein 3 (UCP3), OB-Rb, Insulin receptor (InsR) and interleukins 6 and 15 (IL6, IL15). There was a decrease in mRNA levels of pyruvate dehydrogenase kinase 4 (PDK4) and mCPT1 in the long-term (24h). PGC1α protein levels were increased (24h). Conclusion: Leptin rapidly induces the expression of genes important for its own response and the control of metabolic fuels, with the rapid responses of the genes encoding the master regulator PGC1α, mCPT1, UCP3, PDK4 and the signaling secretory molecule IL6 particularly interesting.

scholarly journals Liraglutide suppresses obesity and promotes browning of white fat via miR-27b in vivo and in vitro

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110550
Author(s):  
Xing Wang ◽  
Shuchun Chen ◽  
Dan Lv ◽  
Zelin Li ◽  
Luping Ren ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
White Adipocytes ◽  
White Fat

Objective To investigate the effect of liraglutide on the browning of white fat and the suppression of obesity via regulating microRNA (miR)-27b in vivo and in vitro. Methods Sprague-Dawley rats were fed a high-fat (HF) diet and 3T3-L1 pre-adipocytes were differentiated into mature white adipocytes. Rats and mature adipocytes were then treated with different doses of liraglutide. The mRNA and protein levels of browning-associated proteins, including uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), CCAAT enhancer binding protein β (CEBPβ), cell death-inducing DFFA-like effector A (CIDEA) and peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α), were detected using quantitative real-time polymerase chain reaction and Western blotting. Results Liraglutide decreased body weight and reduced the levels of blood glucose, triglyceride and low-density lipoprotein cholesterol in HF diet-fed rats. Liraglutide increased the levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α in vivo and vitro. The levels of miR-27b were upregulated in HF diet-fed rats, whereas liraglutide reduced the levels of miR-27b. In vitro, overexpression of miR-27b decreased the mRNA and protein levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α. Transfection with the miR-27b mimics attenuated the effect of liraglutide on the browning of white adipocytes. Conclusion Liraglutide induced browning of white adipose through regulation of miR-27b.

scholarly journals Current Progress in Adipose Tissue Biology: Implications in Obesity and Its Comorbidities

2020 ◽  
Vol 12 (2) ◽  
pp. 85-101
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Common Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Brown Adipose ◽  
Key Factor ◽  
Beige Fat

BACKGROUND: Obesity has been decades become a highly interest study, accompanied by the realization that adipose tissue (AT) plays a major role in the regulation of metabolic function.CONTENT: In past few years, adipocytes classification, development, and differentiation has been significant changes. The white adipose tissue (WAT) can transform to a phenotype like brown adipose (BAT) type and function. Exercise and cold induction were the most common factor for fat browning; however batokines such as fibroblast growth factor (FGF)-21, interleukin (IL)-6, Slit homolog 2 protein (SLIT2)-C, and Meteorin-like protein (METRNL) perform a beneficial browning action by increasing peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α protein levels, a key factor to stimulate mitochondrial biogenesis and uncoupling Protein 1 (UCP1) transcription, thus change the WAT phenotype into beige.SUMMARY: AT recently known as a complex organ, not only bearing a storage function but as well as the master regulator of energy balance and nutritional homeostasis; brown and beige fat express constitutively high levels of thermogenic genes and raise our expectation on new strategies for fighting obesity and metabolic disorders.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, inflammation, IR, metabolic disease

Abstract 1729: PPARγ Regulates ABCG1 Expression in Macrophages via LXR-Driven Dual Promoters

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Makoto Ayaori ◽  
Masatsune Ogura ◽  
Kazuhiro Nakaya ◽  
Tetsuya Hisada ◽  
Shun-ichi Takiguchi ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Exon 1 ◽  
Dual Promoters ◽  
Sirna Knockdown

ATP binding cassette transporter G1 (ABCG1), which is expressed in macrophages, has been implicated in the efflux of cholesterol to high density lipoprotein. Peroxisome proliferator-activated receptor γ (PPARγ) has been reported to be involved in cholesterol efflux from macrophages, and increased expression of ABCG1 via liver receptor X (LXR)-dependent and independent pathways. However, the mechanisms by which ABCG1 expression is increased by PPARγ have not been fully characterized. We observed that pioglitazone, a PPARγ ligand, increases cholesterol efflux from THP-1 macrophages, as well as ABCG1 mRNA and protein levels. Treatment with actinomycin D abolished the inducible effect of pioglitazone on ABCG1, indicating that pioglitazone transcriptionally activated ABCG1 expression. To clarify how pioglitazone regulates ABCG1 expression, we investigated promoter activity using reporter constructs containing human ABCG1 promoter A and B (located upstream of exon 1 and 5, respectively), with or without mutated LXR-binding sites. The results indicated that pioglitazone activated both promoters in an LXR-dependent manner. We also observed that pioglitazone increased two major transcripts driven by promoter A and B using specific primers for each transcript. To determine whether PPARγ and LXRα were involved in these effects of pioglitazone, we performed siRNA-knockdown of PPARγ and LXRα in macrophages, which resulted in 75% and 91% decreases in PPARγ and LXRα mRNA levels, respectively. PPARγ and LXRα-knockdown, respectively, completely or partially abolished pioglitazone-induced ABCG1 expression. In conclusion, these results suggest that pioglitazone transcriptionally increased ABCG1 expression in macrophages by activating dual promoters in an LXR-dependent manner. Further studies are needed to assess LXR-independent mechanisms for the stimulatory effect of pioglitazone on ABCG1.

scholarly journals Tissue-specific induction of 17 beta-hydroxysteroid dehydrogenase type IV by peroxisome proliferator chemicals is dependent on the peroxisome proliferator-activated receptor alpha

1998 ◽  
Vol 158 (2) ◽  
pp. 237-246 ◽  
Author(s):  
LQ Fan ◽  
RC Cattley ◽  
JC Corton
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Ppar Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha ◽  
Protein Levels ◽  
Type Iv ◽  
Liver And Kidney ◽  
The Impact

The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) family of proteins regulates the levels of the active 17 beta-hydroxy forms of sex steroids. The expression of 17 beta-HSD type IV is induced by peroxisome proliferator chemicals (PPC) in rat liver. In order to characterize more generally the impact of PPC on 17 beta-HSD expression, we determined (1) if expression of other members of the 17 beta-HSD family was coordinately induced by PPC exposure, (2) the tissues in which 17 beta-HSD was induced by PPC, and (3) whether the induction of 17 beta-HSD by PPC was dependent on the peroxisome proliferator-activated receptor alpha (PPAR alpha), the central mediator of PPC effects in the mouse liver. The mRNA levels of 17 beta-HSD I, II, and III were not altered in the liver, kidney, and testis or uterus of rats treated with PPC. The mRNA or 80 kDa a full-length protein levels of 17 beta-HSD IV were strongly induced in liver and kidney, but not induced in adrenals, brown fat, heart, testis, and uterus of rats treated with diverse PPC. In liver and kidneys from treated rats, additional proteins of 66 kDa, 56 kDa, and 32 kDa were also induced which reacted with the anti-17 beta-HSD IV antibodies and were most likely proteolytic fragments of 17 bega-HSD IV. Treatment of mice which lack a functional form of PPAR alpha with PPC, demonstrated that PPC-inducibility of 17 beta-HSD IV mRNA or the 80 kDa protein was dependent on PPAR alpha expression in liver and kidney. Our results demonstrate that 17 beta-HSD IV is induced by PPC through a PPAR alpha-dependent mechanism and support the hypothesis that exposure to PPC leads to alterations in sex steroid metabolism.

scholarly journals Sex Difference in Hepatic Peroxisome Proliferator-Activated Receptor α Expression: Influence of Pituitary and Gonadal Hormones

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Masoumeh Jalouli ◽  
Linda Carlsson ◽  
Caroline Améen ◽  
Daniel Lindén ◽  
Anna Ljungberg ◽  
...  
Keyword(s):  
Sex Difference ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Male Rats ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Gh Treatment ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Secretory Pattern

Abstract Peroxisome proliferator-activated receptor (PPAR) α is a nuclear receptor that is mainly expressed in tissues with a high degree of fatty acid oxidation such as liver, heart, and skeletal muscle. Unsaturated fatty acids, their derivatives, and fibrates activate PPARα. Male rats are more responsive to fibrates than female rats. We therefore wanted to investigate if there is a sex difference in PPARα expression. Male rats had higher levels of hepatic PPARα mRNA and protein than female rats. Fasting increased hepatic PPARα mRNA levels to a similar degree in both sexes. Gonadectomy of male rats decreased PPARα mRNA expression to similar levels as in intact and gonadectomized female rats. Hypophysectomy increased hepatic PPARα mRNA and protein levels. The increase in PPARα mRNA after hypophysectomy was more pronounced in females than in males. GH treatment decreased PPARα mRNA and protein levels, but the sex-differentiated secretory pattern of GH does not determine the sex-differentiated expression of PPARα. The expression of PPARα mRNA in heart or soleus muscle was not influenced by gender, gonadectomy, hypophysectomy, or GH treatment. In summary, pituitary-dependent hormones specifically regulate hepatic PPARα expression. Sex hormones regulate the sex difference in hepatic PPARα levels, but not via the sexually dimorphic GH secretory pattern.

scholarly journals Activation of alternative NF-κB signaling during recovery of disuse-induced loss of muscle oxidative phenotype

2014 ◽  
Vol 306 (6) ◽  
pp. E615-E626 ◽  
Author(s):  
A. H. V. Remels ◽  
N. A. Pansters ◽  
H. R. Gosker ◽  
A. M. W. J. Schols ◽  
R. C. J. Langen
Keyword(s):  
Molecular Mechanisms ◽  
Myosin Heavy Chain Isoforms ◽  
Sirtuin 1 ◽  
Hindlimb Suspension ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Levels ◽  
Protein Levels ◽  
Oxidative Phenotype

Physical inactivity-induced loss of skeletal muscle oxidative phenotype (OXPHEN), often observed in chronic disease, adversely affects physical functioning and quality of life. Potential therapeutic targets remain to be identified, since the molecular mechanisms involved in reloading-induced recovery of muscle OXPHEN remain incompletely understood. We hypothesized a role for alternative NF-κB, as a recently identified positive regulator of muscle OXPHEN, in reloading-induced alterations in muscle OXPHEN. Markers and regulators (including alternative NF-κB signaling) of muscle OXPHEN were investigated in gastrocnemius muscle of mice subjected to a hindlimb suspension/reloading (HLS/RL) protocol. Expression levels of oxidative phosphorylation subunits and slow myosin heavy chain isoforms I and IIA increased rapidly upon RL. After an initial decrease upon HLS, mRNA levels of peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC) molecules PGC-1α and PGC-1β and mRNA levels of mitochondrial transcription factor A (Tfam) and estrogen-related receptor α increased upon RL. PPAR-δ, nuclear respiratory factor 1 (NRF-1), NRF-2α, and sirtuin 1 mRNA levels increased during RL although expression levels were unaltered upon HLS. In addition, both Tfam and NRF-1 protein levels increased significantly during the RL period. Moreover, upon RL, IKK-α mRNA and protein levels increased, and phosphorylation of P100 and subsequent processing to P52 were elevated, reflecting alternative NF-κB activation. We conclude that RL-induced recovery of muscle OXPHEN is associated with activation of alternative NF-κB signaling.

Interactions between ROS and AMP kinase activity in the regulation of PGC-1α transcription in skeletal muscle cells

2009 ◽  
Vol 296 (1) ◽  
pp. C116-C123 ◽  
Author(s):  
Isabella Irrcher ◽  
Vladimir Ljubicic ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Promoter Activity ◽  
Muscle Cells ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Ros Production ◽  
Ampk Activation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects

Reactive oxygen species (ROS) play an important role in cellular function via the activation of signaling cascades. ROS have been shown to affect mitochondrial biogenesis, morphology, and function. Their beneficial effects are likely mediated via the upregulation of transcriptional regulators such as peroxisome proliferator-activated receptor-γ coactivator-1 protein-α (PGC-1α). However, the ROS signals that regulate PGC-1α transcription in skeletal muscle are not understood. Here we examined the effect of H2O2 on the regulation of PGC-1α expression, and its relationship to AMPK activation. We demonstrate that 24 h of exogenous H2O2 treatment increased PGC-1α promoter activity and mRNA expression. Both effects were blocked with the addition of N-acetylcysteine, a ROS scavenger. These effects were mediated, in part, via upstream stimulatory factor-1/Ebox DNA binding and involved 1) interactions with downstream sequences and 2) the activation of AMPK. Elevated ROS led to the activation of AMPK, likely via a decline in ATP levels. The activation of AMPK using 5-aminoimidazole-4-carboxamide-1-β- d-ribofuranoside increased PGC-1α promoter activity and mRNA levels but reduced ROS production. Thus the net effect of AMPK activation on PGC-1α expression was a result of increased transcriptional activation, counterbalanced by reduced ROS production. The effects of H2O2 on PGC-1α expression differed depending on the level of ROS within the cell. Low levels of ROS result in reduced PGC-1α mRNA in the absence of an effect on PGC-1α promoter activation. In contrast, elevated levels of H2O2 induce PGC-1α transcription indirectly, via AMPK activation. These data identify unique interactions between ROS and AMPK activation on the expression of PGC-1α in muscle cells.

Molecular mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells

2006 ◽  
Vol 290 (5) ◽  
pp. E916-E924 ◽  
Author(s):  
Juan Kong ◽  
Yan Chun Li
Keyword(s):  
Cell Differentiation ◽  
Molecular Mechanism ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Dihydroxyvitamin D3 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels

We have investigated the molecular mechanism whereby 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibits adipogenesis in vitro. 1,25(OH)2D3 blocks 3T3-L1 cell differentiation into adipocytes in a dose-dependent manner; however, the inhibition is ineffective 24–48 h after the differentiation is initiated, suggesting that 1,25(OH)2D3 inhibits only the early events of the adipogenic program. Treatment of 3T3-L1 cells with 1,25(OH)2D3 does not block the mitotic clonal expansion or C/EBPβ induction; rather, 1,25(OH)2D3 blocks the expression of C/EBPα, peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein-1, and other downstream adipocyte markers. The inhibition by 1,25(OH)2D3 is reversible, since removal of 1,25(OH)2D3 from the medium restores the adipogenic process with only a temporal delay. Interestingly, although the vitamin D receptor (VDR) protein is barely detectable in 3T3-L1 preadipocytes, its levels are dramatically increased during the early phase of adipogenesis, peaking at 4–8 h and subsiding afterward throughout the rest of the differentiation program; 1,25(OH)2D3 treatment appears to stabilize the VDR protein levels. Consistently, adenovirus-mediated overexpression of human (h) VDR in 3T3-L1 cells completely blocks the adipogenic program, confirming that VDR is inhibitory. Inhibition of adipocyte differentiation by 1,25(OH)2D3 is ameliorated by troglitazone, a specific PPARγ antagonist; conversely, hVDR partially suppresses the transacting activity of PPARγ but not of C/EBPβ or C/EBPα. Moreover, 1,25(OH)2D3 markedly suppresses C/EBPα and PPARγ mRNA levels in mouse epididymal fat tissue culture. Taken together, these data indicate that the blockade of 3T3-L1 cell differentiation by 1,25(OH)2D3 occurs at the postclonal expansion stages and involves direct suppression of C/EBPα and PPARγ upregulation, antagonization of PPARγ activity, and stabilization of the inhibitory VDR protein.

scholarly journals The effect of omega3 fatty acid supplementation on PPARγ and UCP2 expressions, resting energy expenditure, and appetite in athletes

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sara Moradi ◽  
Mohamadreza Alivand ◽  
Yaser KhajeBishak ◽  
Mohamad AsghariJafarabadi ◽  
Maedeh Alipour ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Mrna Expression ◽  
Resting Energy Expenditure ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Double Blind ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Ucp2 Mrna ◽  
Resting Energy

Abstract Background Omega3 fatty acids as a ligand of energy-related genes, have a role in metabolism, and energy expenditure. These effects are due to changes in the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) and uncoupling protein2 (UCP2). This study evaluated the effect of omega3 supplements on PPARγ mRNA expression and UCP2 mRNA expression and protein levels, as regulators of energy metabolism, resting energy expenditure (REE), and appetite in athletes. Methods In a 3-week double-blind RCT in Tabriz, Iran, in 2019, 36 male athletes, age 21.86 (±3.15) y with 16.17 (±5.96)% body fat were randomized to either an intervention (2000 mg/day omega3; EPA: 360, DHA: 240) or placebo (2000 mg/day edible paraffin) groups. Appetite and REE were assessed before and after the intervention. PPARγ and UCP2 mRNA expression and UCP2 protein levels in blood were evaluated by standard methods. Results Results showed PPARγ mRNA levels, and UCP2 mRNA and protein levels increased in omega3 group (p < 0.05), as did REE (p < 0.05). Also, differences in the sensation of hunger or satiety were significant (p < 0.05). Conclusions Our findings showed that omega3 supplementation leads to the up-regulation of PPARγ and UCP2 expressions as the indicators of metabolism in healthy athletes.

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