scholarly journals Proteomic and Transcriptomic Changes in Hibernating Grizzly Bears Reveal Metabolic and Signaling Pathways that Protect against Muscle Atrophy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
D. A. Mugahid ◽  
T. G. Sengul ◽  
X. You ◽  
Y. Wang ◽  
L. Steil ◽  
...  

AbstractMuscle atrophy is a physiological response to disuse and malnutrition, but hibernating bears are largely resistant to this phenomenon. Unlike other mammals, they efficiently reabsorb amino acids from urine, periodically activate muscle contraction, and their adipocytes differentially responds to insulin. The contribution of myocytes to the reduced atrophy remains largely unknown. Here we show how metabolism and atrophy signaling are regulated in skeletal muscle of hibernating grizzly bear. Metabolic modeling of proteomic changes suggests an autonomous increase of non-essential amino acids (NEAA) in muscle and treatment of differentiated myoblasts with NEAA is sufficient to induce hypertrophy. Our comparison of gene expression in hibernation versus muscle atrophy identified several genes differentially regulated during hibernation, including Pdk4 and Serpinf1. Their trophic effects extend to myoblasts from non-hibernating species (including C. elegans), as documented by a knockdown approach. Together, these changes reflect evolutionary favored adaptations that, once translated to the clinics, could help improve atrophy treatment.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark G. Sterken ◽  
Marijke H. van Wijk ◽  
Elizabeth C. Quamme ◽  
Joost A. G. Riksen ◽  
Lucinda Carnell ◽  
...  

AbstractEthanol-induced transcriptional changes underlie important physiological responses to ethanol that are likely to contribute to the addictive properties of the drug. We examined the transcriptional responses of Caenorhabditis elegans across a timecourse of ethanol exposure, between 30 min and 8 h, to determine what genes and genetic pathways are regulated in response to ethanol in this model. We found that short exposures to ethanol (up to 2 h) induced expression of metabolic enzymes involved in metabolizing ethanol and retinol, while longer exposure (8 h) had much more profound effects on the transcriptome. Several genes that are known to be involved in the physiological response to ethanol, including direct ethanol targets, were regulated at 8 h of exposure. This longer exposure to ethanol also resulted in the regulation of genes involved in cilia function, which is consistent with an important role for the effects of ethanol on cilia in the deleterious effects of chronic ethanol consumption in humans. Finally, we found that food deprivation for an 8-h period induced gene expression changes that were somewhat ameliorated by the presence of ethanol, supporting previous observations that worms can use ethanol as a calorie source.


Nematology ◽  
2008 ◽  
Vol 10 (4) ◽  
pp. 539-544 ◽  
Author(s):  
Nancy Lu ◽  
Xiaoyan Xiong

AbstractCurrent Caenorhabditis elegans Maintenance Medium (C-CeMM) is used to cultivate the free-living nematode, C. elegans. In C-CeMM, ten amino acids (AA) were found to be nutritionally essential. The optimal requirements of seven of these ten essential AA were determined previously. The objectives of the present study were to determine the optimal requirements of the remaining three essential AA: histidine, lysine and threonine. The Optimal Caenorhabditis elegans Maintenance Medium (O-CeMM) was formulated using the levels of all essential AA that supported the optimal population growth for C. elegans from previous quantitative studies and from the results obtained in the first part of this study. The efficacy of O-CeMM, C-CeMM, as well as Egg CeMM (E-CeMM), based on the essential AA ratio in hen's egg, was studied. The optimal requirements (mg ml–1) of histidine, lysine and threonine were determined to be 2.26 (8× C-CeMM), 1.03-2.06 (1× to 2× C-CeMM), and 0.717-2.86 (1× to 4× C-CeMM), respectively. It was found that O-CeMM supported a significantly higher (1.55 ∼ 1.60×) population growth (number of nematodes/ml) when compared with C-CeMM and E-CeMM. For both O-CeMM and C-CeMM, the AA efficiency ratio (AAER; g dry weight (wt) gain of C. elegans/g of total AA) was determined to be 0.18, which was significantly higher than the 0.15 that was determined in E-CeMM. Although the O-CeMM supported a significantly higher population growth, a higher level of histidine and consequently higher total AA were used in O-CeMM than in C-CeMM. Therefore, based on the findings on AAER, it was concluded that both the O-CeMM and C-CeMM were equally efficient for the cultivation of C. elegans.


2022 ◽  
Author(s):  
Berra Erkosar ◽  
Cindy Dupuis ◽  
Fanny Cavigliasso ◽  
Loriane Savary ◽  
Hector Gallart-Ayala ◽  
...  

Juveniles are often first to suffer from nutrient shortage, and juvenile undernutrition is likely an important force of natural selection shaping animal physiology, with consequences potentially extending into adulthood. We combined RNAseq, targeted metabolomics and genomics to study the consequences of experimental evolution under juvenile undernutrition for metabolism of reproductively active adult females of Drosophila melanogaster. Compared to six Control populations maintained on standard diet, six Selected populations evolved for over 230 generations on a nutrient-poor larval diet showed major changes in adult gene expression and metabolite abundance. In particular, Selected flies were relatively deficient in essential amino acids and purine nucleotides, but showed overabundance of several non-essential amino-acids involved in purine synthesis and overexpression of multiple enzymes catalyzing this pathway. Selected flies also accumulated medium-chain acylcarnitines suggestive of congestion in beta-oxidation, possibly linked to deficiency of electron transporters. Some aspects of the metabolic profile of Selected flies resembled that of flies subject to starvation. Furthermore, differences between Selected and Control populations in adult gene expression were in general positively correlated with differences in larval expression, consistent with pleiotropy in gene regulation between the life stages. Finally, Selected flies were less fit in terms of fecundity than Controls even when both were raised under the conditions under which the Selected populations evolved. These results suggest that evolutionary adaptation to juvenile undernutrition has large pleiotropic consequences for adult metabolism, and that they are costly rather than adaptive for adult fitness.


1999 ◽  
Vol 58 (3) ◽  
pp. 625-632 ◽  
Author(s):  
Alain Bruhat ◽  
Céline Jousse ◽  
Pierre Fafournoux

In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.


2018 ◽  
Author(s):  
Yasmine J. Liu ◽  
Georges E. Janssens ◽  
Rashmi Kamble ◽  
Arwen W. Gao ◽  
Aldo Jongejan ◽  
...  

AbstractThe deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids decline with age in Caenorhabditis elegans (C. elegans). Glycine, in contrast, substantially accumulates in aging C. elegans. In this study we show that this is coupled to a decrease in gene expression of enzymes important for glycine catabolism. We further show that supplementation of glycine significantly prolongs C. elegans lifespan and ameliorates specific transcriptional changes that are associated with aging. Glycine feeds into the methionine cycle. We find that mutations in components of this cycle, methionine synthase (metr-1) and S-adenosylmethionine synthetase (sams-1), completely abrogate glycine-induced lifespan extension. Strikingly, the beneficial effects of glycine supplementation are conserved when we supplement with serine, also driving the methionine cycle. RNA sequencing of serine- and glycine-supplemented worms reveals similar transcriptional profiles including widespread gene suppression. Taken together, these data uncover a novel role of glycine in the deceleration of aging through its function in the methionine cycle.Author summaryThere are a growing number of studies showing that amino acids function as signal metabolites that influence aging and health. Although contemporary -OMICs studies have uncovered various associations between metabolite levels and aging, in many cases the directionality of the relationships is unclear. In a recent metabolomics study, we found that glycine accumulates in aged C. elegans while other amino acids decrease. The present study shows that glycine supplementation prolongs longevity and drives a genome-wide inhibition effect on C. elegans gene expression. Glycine as a one-carbon donor fuels the methyl pool of one-carbon metabolism composed of folates and methionine cycle. We find that glycine-mediated longevity effect is fully dependent on methionine cycle, and that all of these observations are conserved with supplementation of the other one-carbon amino acid, serine. These results provide a novel role for glycine as a promoter of longevity and bring new insight into the role of one-carbon amino acids in the regulation of aging that may ultimately be beneficial for humans.


2017 ◽  
Vol 199 (15) ◽  
Author(s):  
Nana Y. D. Ankrah ◽  
Junbo Luan ◽  
Angela E. Douglas

ABSTRACT An important factor determining the impact of microbial symbionts on their animal hosts is the balance between the cost of nutrients consumed by the symbionts and the benefit of nutrients released back to the host, but the quantitative significance of nutrient exchange in symbioses involving multiple microbial partners has rarely been addressed. In this study on the association between two intracellular bacterial symbionts, “Candidatus Portiera aleyrodidarum” and “Candidatus Hamiltonella defensa,” and their animal host, the whitefly Bemisia tabaci, we apply metabolic modeling to investigate host-symbiont nutrient exchange. Our in silico analysis revealed that >60% of the essential amino acids and related metabolites synthesized by “Candidatus Portiera aleyrodidarum” are utilized by the host, including a substantial contribution of nitrogen recycled from host nitrogenous waste, and that these interactions are required for host growth. In contrast, “Candidatus Hamiltonella defensa” retains most or all of the essential amino acids and B vitamins that it is capable of synthesizing. Furthermore, “Candidatus Hamiltonella defensa” suppresses host growth in silico by competition with “Candidatus Portiera aleyrodidarum” for multiple host nutrients, by suppressing “Candidatus Portiera aleyrodidarum” growth and metabolic function, and also by consumption of host nutrients that would otherwise be allocated to host growth. The interpretation from these modeling outputs that “Candidatus Hamiltonella defensa” is a nutritional parasite could not be inferred reliably from gene content alone but requires consideration of constraints imposed by the structure of the metabolic network. Furthermore, these quantitative models offer precise predictions for future experimental study and the opportunity to compare the functional organization of metabolic networks in different symbioses. IMPORTANCE The metabolic functions of unculturable intracellular bacteria with much reduced genomes are traditionally inferred from gene content without consideration of how the structure of the metabolic network may influence flux through metabolic reactions. The three-compartment model of metabolic flux between two bacterial symbionts and their insect host constructed in this study revealed that one symbiont is structured to overproduce essential amino acids for the benefit of the host, but the essential amino acid production in the second symbiont is quantitatively constrained by the structure of its network, rendering it “selfish” with respect to these nutrients. This study demonstrates the importance of quantitative flux data for elucidation of the metabolic function of symbionts. The in silico methodology can be applied to other symbioses with intracellular bacteria.


2021 ◽  
Vol 22 (10) ◽  
pp. 5166
Author(s):  
Qin Lu ◽  
Xiaoming Chen ◽  
Zixiang Yang ◽  
Nawaz Haider Bashir ◽  
Juan Liu ◽  
...  

Chinese galls are the result of hyperplasia in host plants induced by aphids. The metabolism and gene expression of these galls are modified to accommodate the aphids. Here, we highlight the molecular and histologic features of horned galls according to transcriptome and anatomical structures. In primary pathways, genes were found to be unevenly shifted and selectively expressed in the galls and leaves near the galls (LNG). Pathways for amino acid synthesis and degradation were also unevenly shifted, favoring enhanced accumulation of essential amino acids in galls for aphids. Although galls enhanced the biosynthesis of glucose, which is directly available to aphids, glucose content in the gall tissues was lower due to the feeding of aphids. Pathways of gall growth were up-regulated to provide enough space for aphids. In addition, the horned gall has specialized branched schizogenous ducts and expanded xylem in the stalk, which provide a broader feeding surface for aphids and improve the efficiency of transportation and nutrient exchange. Notably, the gene expression in the LNG showed a similar pattern to that of the galls, but on a smaller scale. We suppose the aphids manipulate galls to their advantage, and galls lessen competition by functioning as a medium between the aphids and their host plants.


2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Rahmawati Rahmawati ◽  
Trimayasari Trimayasari ◽  
Ghozali Akhmad Mustaqim ◽  
Wening Dwi Prastiwi ◽  
Emas Agus Prastyo Wibowo

AbstractSoap facial cleanser is needed to keep the facial skin to keep them clean and healthy. The purpose of this study to make soap cleanser with natural materials such as hard water deposits leri. This is because the use of leri water starch or starch granules of fine particles contained in water leri dansel dust can shed the dead skin on the face because of the essential amino acids contained can regenerate skin cells. In addition, water leri can brighten the face because the leri water oryzanol contain substances that can update the development and formation of the pigment melanin, which is effectively to ward off ultraviolet rays. The process of making soap using the principle of saponification reaction, namely the reaction between the oil and the KOH/NaOH. Facial cleansing soap made in this study is solid soap. Based on the results of quality test, soap solid leri water has a pH of 11.1, saponification number is 33, the water content of 46% as well as respondents to the test aspects of aroma and foam shows good results so this water leri treatment can be an alternative solution to prevent the use of soap facial cleansers that contain harmful chemicals. Keywords: air leri, soap cleanser, saponification  AbstrakSabun pembersih wajah sangat diperlukan untuk menjaga kulit wajah agar tetap bersih dan sehat. Tujuan dari penelitian ini untuk membuat sabun pembersih wajah dengan bahan alami berupa endapan air leri. Penggunaan air leri ini dikarenakan butiran partikel starch atau pati halus yang terdapat dalam air leri dapat merontokkan debu dansel kulit mati pada wajah karena asam amino esensial yang terkandung dapat meregenerasi sel-sel kulit. Selain itu, air leri dapat mencerahkan wajah karena air leri mengandung zat oryzanol yang dapat memperbarui perkembangan dan pembentukan pigmen melanin, yang efektif guna menangkal sinar ultraviolet. Proses pembuatan sabun menggunakan prinsip reaksi saponifikasi, yaitu reaksi antara minyak dan KOH/NaOH. Sabun pembersih wajah yang dibuat dalam penelitian ini ialah sabun padat. Berdasarkan hasil uji mutu, sabun air leri padat memiliki pH 11,1, angka penyabunan sebesar 33 kadar air 46 kadar air 46 % serta uji responden terhadap aspek aroma dan busa yang menunjukkan hasil cukup baik sehingga pengolahan air leri ini dapat menjadi solusi alternative untuk mencegah penggunaan sabun pembersih wajah yang mengandung bahan kimia berbahaya. Kata kunci: air leri, sabun pembersih wajah, saponifikasi 


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