scholarly journals Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice

2018 ◽  
Vol 19 (10) ◽  
pp. 2904 ◽  
Author(s):  
Christian Carpéné ◽  
Saioa Gómez-Zorita ◽  
Alice Chaplin ◽  
Josep Mercader
Keyword(s):  
Adipose Tissue ◽  
Phosphoenolpyruvate Carboxykinase ◽  
De Novo ◽  
Uncoupling Protein ◽  
De Novo Lipogenesis ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Brown Adipose ◽  
High Sucrose ◽  
Sucrose Drinking

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.

scholarly journals Eicosapentaenoic Acid Increases Browning Markers in Subcutaneous Adipose Tissue and Primary Adipocytes from Wild Type and UCP-1 Deficient Mice (P15-007-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Shasika Jayarathne ◽  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
Shane Scoggin ◽  
Naima Moustaid-Moussa
Keyword(s):  
Adipose Tissue ◽  
Eicosapentaenoic Acid ◽  
Subcutaneous Adipose Tissue ◽  
Uncoupling Protein ◽  
Fibroblast Growth Factor 21 ◽  
Chow Diet ◽  
Mrna Levels ◽  
Wild Type ◽  
Brown Adipose ◽  
Subcutaneous Adipose

Abstract Objectives Brown adipose tissue (BAT) regulates energy balance through thermogenesis, in part via uncoupling protein -1 (UCP-1). White adipose tissue (WAT), namely subcutaneous adipose tissue (SAT) can convert to a beige/brite adipose tissue phenotype (browning) under thermogenic conditions such as cold. We previously reported that eicosapentaenoic acid (EPA) reduced obesity and glucose intolerance, and increased UCP-1 in BAT of B6 mice at ambient temperature (22°C); and these effects were attenuated at thermoneutral environment (28–30°C). We hypothesized that EPA exerts anti-obesity effects on SAT, including increased browning, adipocyte hypotrophy; and these effects require UCP-1. Methods Six-week-old B6 wild type (WT) and UCP-1 knock-out (KO) male mice were maintained at thermoneutral environment and fed high fat diet (HF) with or without 36 g/kg of AlaskOmega EPA-enriched fish oil (800 mg/g) for 14 weeks; and SAT was collected for histological, gene and protein analyses. SAT was also prepared from chow diet-fed WT and KO mice at ambient environment to prepare stroma vascular cells, which were differentiated into adipocytes, treated with 100uM EPA for 48 hours then harvested for mRNA and protein analyses. Results KO mice fed HF diets had the highest body weight (P < 0.05) among all groups. EPA reduced fat cell size in both WT and KO mice fed the EPA diet. mRNA levels of fibroblast growth factor-21 (FGF-21) were higher in SAT of WT mice fed EPA compared to WT mice fed HF (P < 0.05), with no differences between the KO genotype. KO mice fed HF diets had lower levels of UCP-3 in SAT compared to WT mice fed HF (P < 0.05), which was rescued only in the KO mice fed EPA (P < 0.05). UCP-1 protein levels were very low in SAT tissues, and UCP-2 mRNA levels were similar across all groups in SAT. Interestingly, EPA significantly (P < 0.05) increased mRNA expression of UCP-2, UCP-3 and FGF21 in differentiated SAT adipocytes from both WT and KO compared to control. Furthermore, UCP-1 mRNA levels were significantly higher in WT adipocytes treated with EPA, compared to non-treated cells (P < 0.05). Additional mechanistic studies are currently underway to further dissect adipose depot differences in EPA effects in WT vs. KO mice. Conclusions Our data suggest that EPA increases SAT browning, independently of UCP-1. Funding Sources NIH/NCCIH.

46 Inhibition of Lipolysis with Acipimox Targets Post-burn White Adipose Browning by Altering Macrophage Polarity

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S30-S31
Author(s):  
Dalia Barayan ◽  
Roohi Vinaik ◽  
Marc G Jeschke
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Polarization State ◽  
Critical Role ◽  
Metabolic Effects ◽  
Inhibitory Effects ◽  
Macrophage Recruitment ◽  
M2 Polarization ◽  
Brown Adipose ◽  
Major Burn

Abstract Introduction Severe burns are accompanied by a detrimental hypermetabolic stress response that can persist for years post-injury. Our previous work revealed that, under prolonged stress, white adipose tissue (WAT) adopts brown adipose-like traits in a process termed ‘browning’. This switch, characterized by the presence of uncoupling protein 1 (UCP1), is driven by the polarization of macrophages towards an M2 phenotype. Recently, we demonstrated that inhibiting lipolysis with the clinically approved drug, Acipimox, represses the burn-induced thermogenic activation of WAT. These findings raise the possibility that elevated rates of lipolysis may play a role in regulating the macrophage polarization state after major burn. However, the interconnection between post-burn lipolysis and inflammation remains unclear. In the present study, we investigated the mechanism underlying Acipimox’s inhibitory effects on burn-induced browning. Using a mouse model of thermal injury, we determine the metabolic effects of reducing WAT lipolysis on burn-induced macrophage recruitment and M2-polarization. Methods Adult C57BL/6 mice received a 30% total body surface area scald burn. Mice were then given daily intraperitoneal injections of APX (50 mg/Kg). On day 7 post-burn, the inguinal adipose tissue depot (iWAT) was harvested for histological analyses. Flow cytometry and F4/80 staining were used to assess adipose macrophage distribution and profile, and gene expression was analyzed via qPCR. Results APX administration significantly increased mitochondrial coupling, reflected by the decrease in UCP-1 (p&lt; 0.05) and PGC-1a (p&lt; 0.01) levels relative to the iWAT of untreated burn mice. F4/80 immunostaining of iWAT demonstrated decreased macrophage recruitment in Acipimox treated mice (p&lt; 0.05). Flow cytometric analysis indicated decreased macrophage infiltration at 7 days in Acipimox treated mice (p&lt; 0.05). Furthermore, iWAT from Acipimox treated mice demonstrated a pro-inflammatory profile, indicated by a greater distribution of TLR4 positive macrophages (p&lt; 0.05). Conclusions Previously, we showed that the administration of Acipimox effectively suppressed PKA-mediated lipolysis and improved mitochondrial coupling in adipose tissue post-burn. Here, we elucidate the mechanism underlying these metabolic changes. Importantly, we show Acipimox exerts its inhibitory effects on burn-induced WAT browning by directly modulating macrophage recruitment and the M2-polarization state. Applicability of Research to Practice Our study highlights the critical role of lipolysis in mediating the key post-burn metabolic phenomena browning and inflammation. The data presented herein validate the pharmacological inhibition of lipolysis as a potentially powerful therapeutic strategy to counteract the detrimental metabolic effects induced by burn.

scholarly journals Vitamin D Supplementation Improves Adipose Tissue Inflammation and Reduces Hepatic Steatosis in Obese C57BL/6J Mice

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 342 ◽  
Author(s):  
Alexandra Marziou ◽  
Clothilde Philouze ◽  
Charlène Couturier ◽  
Julien Astier ◽  
Philippe Obert ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Triglyceride Accumulation

The beneficial effect of vitamin D (VD) supplementation on body weight gain limitation and inflammation has been highlighted in primary prevention mice models, but the long-term effect of VD supplementation in tertiary prevention has never been reported in obesity models. The curative effect of VD supplementation on obesity and associated disorders was evaluated in high-fat- and high-sucrose (HFS)-fed mice. Morphological, histological, and molecular phenotype were characterized. The increased body mass and adiposity caused by HFS diet as well as fat cell hypertrophy and glucose homeostasis were not improved by VD supplementation. However, VD supplementation led to a decrease of HFS-induced inflammation in inguinal adipose tissue, characterized by a decreased expression of chemokine mRNA levels. Moreover, a protective effect of VD on HFS-induced hepatic steatosis was highlighted by a decrease of lipid droplets and a reduction of triglyceride accumulation in the liver. This result was associated with a significant decrease of gene expression coding for key enzymes involved in hepatic de novo lipogenesis and fatty acid oxidation. Altogether, our results show that VD supplementation could be of interest to blunt the adipose tissue inflammation and hepatic steatosis and could represent an interesting nutritional strategy to fight obesity-associated comorbidities.

scholarly journals Dissociation between adipose tissue fluxes and lipogenic gene expression in ob/ob mice

2007 ◽  
Vol 292 (4) ◽  
pp. E1101-E1109 ◽  
Author(s):  
S. M. Turner ◽  
S. Roy ◽  
H. S. Sul ◽  
R. A. Neese ◽  
E. J. Murphy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Adipose Tissue ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Mrna Levels ◽  
Lipogenic Genes ◽  
Lipogenic Gene Expression ◽  
Leptin Deficiency ◽  
Normal Expression

Recent evidence has been presented that expression of lipogenic genes is downregulated in adipose tissue of ob/ob mice as well as in human obesity, suggesting a functionally lipoatrophic state. Using 2H2O labeling, we measured three adipose tissue biosynthetic processes concurrently: triglyceride (TG) synthesis, palmitate de novo lipogenesis (DNL), and cell proliferation (adipogenesis). To determine the effect of the ob/ob mutation (leptin deficiency) on these parameters, adipose dynamics were compared in ob/ob, leptin-treated ob/ob, food-restricted ob/ob, and lean control mice. Adipose tissue fluxes for TG synthesis, de novo lipogenesis (DNL), and adipogenesis were dramatically increased in ob/ob mice compared with lean controls. Low-dose leptin treatment (2 μg/day) via miniosmotic pump suppressed all fluxes to control levels or below. Food restriction in ob/ob mice only modestly reduced DNL, with no change in TG synthesis or adipogenesis. Measurement of mRNA levels in age-matched ob/ob mice showed generally normal expression levels for most of the selected lipid anabolic genes, and leptin treatment had, with few exceptions, only modest effects on their expression. We conclude that leptin deficiency per se results in marked elevations in flux through diverse lipid anabolic pathways in adipose tissue (DNL, TG synthesis, and cell proliferation), independent of food intake, but that gene expression fails to reflect these changes in flux.

scholarly journals Postnatal selective suppression of lipoprotein lipase gene expression in brown adipose tissue (relative to the expression of the gene for the uncoupling protein) is not due to adrenergic insensitivity: a possible specific inhibitory effect of colostrum

1996 ◽  
Vol 314 (1) ◽  
pp. 261-267 ◽  
Author(s):  
María-Jesus OBREGÓN ◽  
Barbara CANNON ◽  
Jan NEDERGAARD
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Selective Suppression ◽  
Brown Adipose ◽  
Adrenergic Antagonist ◽  
Lpl Gene

The levels of mRNA coding for the uncoupling protein (UCP) and for lipoprotein lipase (LPL) were monitored in the brown adipose tissue of newborn rat pups. At 5 h after birth, the mRNA levels of UCP and LPL were high in pups exposed singly to 28 °C and low in pups kept singly at thermoneutrality (36 °C); in pups staying with the dam, the UCP mRNA levels were intermediate. However, the LPL mRNA levels were lower in pups staying with the dam than in pups at 36 °C, implying that factors additional to environmental temperature influenced LPL gene expression. Injection of noradrenaline into pups at thermoneutrality (36 °C) led to increases in UCP and LPL gene expression, but noradrenaline injections had no further effect in cold-exposed pups. The adrenergic effects were mediated via β-adrenergic receptors. The cold-induced increases in both UCP and LPL gene expression were abolished by the β-adrenergic antagonist propranolol. Thus differences in adrenergic responsiveness could not explain the differential expression of the UCP and LPL genes observed in pups staying with the dam. The presence of a physiological suppressor was examined by feeding single pups at 28 °C with different foods: nothing, water, Intralipid, cow's milk, rat milk and rat colostrum. None of these agents led to suppression of UCP gene expression, but colostrum led to a selective suppression of LPL gene expression. It was concluded that the genes for UCP and LPL were responsive to adrenergic stimuli immediately after birth, and it is suggested that a component of rat colostrum can selectively suppress LPL gene expression.

scholarly journals Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states

2010 ◽  
Vol 299 (3) ◽  
pp. R728-R739 ◽  
Author(s):  
Barbara E. Hasek ◽  
Laura K. Stewart ◽  
Tara M. Henagan ◽  
Anik Boudreau ◽  
Natalie R. Lenard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Uncoupling Protein ◽  
Nutrient Sensing ◽  
De Novo Lipogenesis ◽  
Endocrine Function ◽  
Fischer 344 ◽  
Methionine Restriction ◽  
Heat Increment

Dietary methionine restriction (MR) is a mimetic of chronic dietary restriction (DR) in the sense that MR increases rodent longevity, but without food restriction. We report here that MR also persistently increases total energy expenditure (EE) and limits fat deposition despite increasing weight-specific food consumption. In Fischer 344 (F344) rats consuming control or MR diets for 3, 9, and 20 mo, mean EE was 1.5-fold higher in MR vs. control rats, primarily due to higher EE during the night at all ages. The day-to-night transition produced a twofold higher heat increment of feeding (3.0°C vs. 1.5°C) in MR vs. controls and an exaggerated increase in respiratory quotient (RQ) to values greater than 1, indicative of the interconversion of glucose to lipid by de novo lipogenesis. The simultaneous inhibition of glucose utilization and shift to fat oxidation during the day was also more complete in MR (RQ ∼0.75) vs. controls (RQ ∼0.85). Dietary MR produced a rapid and persistent increase in uncoupling protein 1 expression in brown (BAT) and white adipose tissue (WAT) in conjunction with decreased leptin and increased adiponectin levels in serum, suggesting that remodeling of the metabolic and endocrine function of adipose tissue may have an important role in the overall increase in EE. We conclude that the hyperphagic response to dietary MR is matched to a coordinated increase in uncoupled respiration, suggesting the engagement of a nutrient-sensing mechanism, which compensates for limited methionine through integrated effects on energy homeostasis.

scholarly journals ChREBP-β regulates thermogenesis in brown adipose tissue

2020 ◽  
Vol 245 (3) ◽  
pp. 343-356 ◽  
Author(s):  
Chunchun Wei ◽  
Xianhua Ma ◽  
Kai Su ◽  
Shasha Qi ◽  
Yuangang Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Critical Role ◽  
Active Form ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Brown Adipose ◽  
Metabolic Remodeling

Brown adipose tissue (BAT) plays a critical role in energy expenditure by uncoupling protein 1 (UCP1)-mediated thermogenesis. Carbohydrate response element-binding protein (ChREBP) is one of the key transcription factors regulating de novo lipogenesis (DNL). As a constitutively active form, ChREBP-β is expressed at extremely low levels. Up to date, its functional relevance in BAT remains unclear. In this study, we show that ChREBP-β inhibits BAT thermogenesis. BAT ChREBP-β mRNA levels were elevated upon cold exposure, which prompted us to generate a mouse model overexpressing ChREBP-β specifically in BAT using the Cre/LoxP approach. ChREBP-β overexpression led to a whitening phenotype of BAT at room temperature, as evidenced by increased lipid droplet size and decreased mitochondrion content. Moreover, BAT thermogenesis was inhibited upon acute cold exposure, and its metabolic remodeling induced by long-term cold adaptation was significantly impaired by ChREBP-β overexpression. Mechanistically, ChREBP-β overexpression downregulated expression of genes involved in mitochondrial biogenesis, autophagy, and respiration. Furthermore, thermogenic gene expression (e.g. Dio2, UCP1) was markedly inhibited in BAT by the overexpressed ChREBP-β. Put together, our work points to ChREBP-β as a negative regulator of thermogenesis in brown adipocytes.

scholarly journals Hepatic ANGPTL3 regulates adipose tissue energy homeostasis

2015 ◽  
Vol 112 (37) ◽  
pp. 11630-11635 ◽  
Author(s):  
Yan Wang ◽  
Markey C. McNutt ◽  
Serena Banfi ◽  
Michael G. Levin ◽  
William L. Holland ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Fed State ◽  
Beneficial Effects ◽  
Brown Adipose

Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3−/− mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3−/− animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3−/− mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target.

scholarly journals Loss of Histone Deacetylase 4 in Hepatocytes Increases De Novo Lipogenesis in Diet-Induced Obesity Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1652-1652
Author(s):  
Yoojin Lee ◽  
Minkyung Bae ◽  
Dana Chamberlain ◽  
Tho Pham ◽  
Hyunju Kang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Histone Deacetylase ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
De Novo ◽  
Blood Analysis ◽  
De Novo Lipogenesis ◽  
Mrna Levels ◽  
Hepatic Expression ◽  
Histone Deacetylase 4

Abstract Objectives Evidence suggests that histone deacetylase 4 (HDAC4) is downregulated in adipose tissue of obese subjects. We determined the role of HDAC4 in the regulation of energy metabolism of metabolically active tissues, such as the liver and adipose tissue. Methods Hepatocyte-specific (Hdac4HKO) and adipocyte-specific (Hdac4AKO) Hdac4 knockout mice were generated by crossing homozygous Hdac4 floxed (Hdac4fl/fl) mice with mice expressing Cre recombinase under the control of the enhancer/promoter of Albumin or Adipoq gene, respectively. Hdac4fl/fl and Hdac4HKO mice were fed a high fat/high sucrose (HF/HS; 57%/28% energy from fat/sucrose) with 2% cholesterol (w/w) diet for 16 weeks. Hdac4fl/fl and Hdac4AKO mice were fed an obesogenic HF/HS diet for 16 weeks. The final serum was collected by cardiopuncture for blood analysis. Tissues were snap frozen for mRNA and protein analysis. Results Both Hdac4HKO and Hdac4AKO mice did not show differences in body weight compared to Hdac4fl/fl mice following the 16-week of experimental diet. However, loss of hepatic HDAC4 increased serum alanine transaminase levels, a marker for liver injury. Also, Hdac4HKO mice had exacerbated hepatic steatosis with higher liver weights and triglyceride levels than Hdac4fl/fl mice. Consistently, hepatic expression of genes for de novo lipogenesis, including Srebf1c and its target genes, fatty acid synthase and acetyl CoA carboxylase 1, was significantly higher in Hdac4HKO mice compared with control mice. Interestingly, the loss of hepatocyte HDAC4 aggravated inflammation and fibrosis in white adipose tissue. Serum cytokine array indicated increases in fibroblast growth factor 1, pentraxin 3, tissue inhibitor of metalloproteinases 1, and decrease in endocan, which may contribute to the crosstalk between the liver and adipose tissue in Hdac4HKO. On the other hand, the loss of adipocyte HDAC4 elicited minimal changes in mRNA levels of lipogenic, inflammatory, and fibrogenic genes in adipose tissue and the liver. Conclusions The lack of functional hepatocyte HDAC4 increased lipid accumulation in the liver of obesity mice via increasing hepatic de novo lipogenesis, and also aggravated adipose tissue inflammation and fibrosis. Further investigation is warranted to elucidate the crosstalk between the liver and adipose tissue in Hdac4HKO. Funding Sources This study was supported by NIH.

Effects of exposure temperature on brown adipose tissue uncoupling protein mRNA levels

1989 ◽  
Vol 67 (2-3) ◽  
pp. 147-151 ◽  
Author(s):  
Karl B. Freeman ◽  
Michael Heffernan ◽  
Zenobia Dhalla ◽  
Hasmukh V. Patel
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Effect Of Temperature ◽  
Initial Time ◽  
Maximal Response ◽  
Mrna Levels ◽  
Exposure Temperature ◽  
Brown Adipose ◽  
Uncoupling Protein Mrna

The effect of temperature on the amount of uncoupling protein mRNA in rat brown adipose tissue was examined after 1 and 14 days of exposure to cold. The relative amounts after 1 day, compared with rats kept at a thermoneutral temperature of 28 °C, were 3.2 at 19 °C, 3.3 at 11 °C, and 2.1 at 3 °C. This suggests that in warm-acclimated rats, a maximal response to a cold stimulus in brown adipose tissue is reached by 19 °C. In contrast to these results, the relative amounts of uncoupling protein mRNA after 14 days of cold exposure, compared with rats left at 28 °C, were 1.2 at 19 °C, 1.9 at 11 °C, and 2.1 at 3 °C. Since it is known that the amount of uncoupling protein in cold-acclimated rats increases continuously with decrease in temperature, the amount of protein reflects the mRNA levels during later times but not the initial time of exposure to cold.Key words: brown adipose tissue, uncoupling protein mRNA.

Sign in / Sign up

Export Citation Format

Share Document