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1.
Sci Rep ; 13(1): 119, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599920

RESUMO

The association between dietary nutrient patterns (NPs) and metabolic health status has not been investigated in adolescents. This study aimed to evaluate the relationship between NPs and metabolic health status in Iranian adolescents with overweight and obesity. In this cross-sectional study, 203 obese/overweight adolescents were selected using a multistage mass random sampling method. To assess usual dietary intakes, a validated food frequency questionnaire was applied. Data of anthropometric and blood pressure were collected. Insulin, lipid profile, and glucose levels were determined using fasting blood samples. Two approaches [International Diabetes Federation (IDF) and a combination of IDF with Homeostasis Model Assessment Insulin Resistance (HOMA-IR)] were applied to identify metabolically healthy obese and metabolically unhealthy obese (MUO) adolescents. Participants had a mean age of 13.9 ± 1.61 years and 52.2% of them were girls. Three NPs were identified and labeled as "high minerals and vitamins" (NP1), "high carbohydrate" (NP2) and "high fat and sodium" (NP3). After adjustments for all potential confounders, no significant association was observed between higher adherence to NP1 and NP2 and odds of MUO; however, greater adherence to "high fat and sodium" NP was associated with higher odds of being MUO based on IDF (OR = 3.12; 95% CI 1.19, 8.09) and IDF/HOMA-IR (OR = 2.81; 95% CI 1.02, 7.74) definitions. Stratified analysis revealed that these associations were stronger in boys (versus girls) and obese (versus overweight) adolescents. In conclusion, high adherence to a "high fat and sodium" nutrient pattern was related to elevated chance of being MUO in Iranian adolescents, especially in boys and obese individuals. Therefore, less consumption of trans fatty acids, saturated fatty acids and sodium could be recommended to prevent MUO prevalence especially in boys with obesity.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Nutrientes , Obesidade Pediátrica , Adolescente , Criança , Feminino , Humanos , Masculino , Índice de Massa Corporal , Estudos Transversais , Nível de Saúde , Irã (Geográfico)/epidemiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Nutrientes/química , Nutrientes/metabolismo , Sobrepeso/epidemiologia , Obesidade Pediátrica/epidemiologia
2.
Trop Anim Health Prod ; 55(1): 17, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36538181

RESUMO

The study investigated the effects of protein replacement with formaldehyde-treated guar meal (FTGM) and prill fat (PF) in the diet on performance of growing dairy buffalo calves. Thirty-two feedlots Surti breed dairy buffalo calves (age, 7.31 ± 0.34 months and body weight, 90.69 ± 6.19 kg) were assigned into four dietary treatments (n-8 calves/each): (1) control group, supplied basal diet as per ICAR (2013) nutrient requirements; (2) FTGM group, 30% crude protein (CP) requirement of concentrate mixture (dry matter basis (DMB)) replaced with FTGM in basal diet; (3) PF group, supplied basal diet + 100 g PF; and (4) FTGM + PF group, 30% CP requirement of concentrate mixture (DMB) replaced with FTGM in the basal diet + 100 g PF for 280 days. All the treatment diets were isonitrogenous. Growth performance was improved in FTGM + PF and FTGM groups. Apparent digestibility (%) of CP was increased in FTGM and FTGM + PF diet, while digestibility (%) of ether extract (EE) was increased in PF group. Serum total protein, albumen, urea nitrogen, and creatinine concentrations were higher in FTGM + PF and FTGM groups, whereas total cholesterol and triglycerides levels were greater in FTGM + PF and PF groups. Calculated methane emission had a discernible influence of treatment in FTGM and FTGM + PF. The overall cost of feeding per kilogram gain was lowest in FTGM and FTGM + PF groups. In conclusion, 30% CP replacement with FTGM with or without PF improved the growth performance, feed conversion ratio, and nutrient utilization; supported efficient utilization of resources; and economized the rearing of growing dairy buffalo calves.


Assuntos
Bison , Cyamopsis , Animais , Búfalos , Rúmen/metabolismo , Ração Animal/análise , Melhoramento Vegetal , Dieta/veterinária , Nutrientes/metabolismo , Formaldeído/metabolismo , Digestão
3.
Nature ; 611(7935): 301-305, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36323777

RESUMO

Enrichment of nutrients and loss of herbivores are assumed to cause a loss of plant diversity in grassland ecosystems because they increase plant cover, which leads to a decrease of light in the understory1-3. Empirical tests of the role of competition for light in natural systems are based on indirect evidence, and have been a topic of debate for the last 40 years. Here we show that experimentally restoring light to understory plants in a natural grassland mitigates the loss of plant diversity that is caused by either nutrient enrichment or the absence of mammalian herbivores. The initial effect of light addition on restoring diversity under fertilization was transitory and outweighed by the greater effect of herbivory on light levels, indicating that herbivory is a major factor that controls diversity, partly through light. Our results provide direct experimental evidence, in a natural system, that competition for light is a key mechanism that contributes to the loss of biodiversity after cessation of mammalian herbivory. Our findings also show that the effects of herbivores can outpace the effects of fertilization on competition for light. Management practices that target maintaining grazing by native or domestic herbivores could therefore have applications in protecting biodiversity in grassland ecosystems, because they alleviate competition for light in the understory.


Assuntos
Biodiversidade , Herbivoria , Luz , Plantas , Animais , Pradaria , Mamíferos/fisiologia , Nutrientes/metabolismo , Plantas/classificação , Plantas/metabolismo , Plantas/efeitos da radiação , Fertilizantes
4.
Nature ; 611(7934): 81-87, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36224391

RESUMO

To meet the growing food demand while addressing the multiple challenges of exacerbating phosphorus (P) pollution and depleting P rock reserves1-15, P use efficiency (PUE, the ratio of productive P output to P input in a defined system) in crop production needs to be improved. Although many efforts have been devoted to improving nutrient management practices on farms, few studies have examined the historical trajectories of PUE and their socioeconomic and agronomic drivers on a national scale1,2,6,7,11,16,17. Here we present a database of the P budget (the input and output of the crop production system) and PUE by country and by crop type for 1961-2019, and examine the substantial contribution of several drivers for PUE, such as economic development stages and crop portfolios. To address the P management challenges, we found that global PUE in crop production must increase to 68-81%, and recent trends indicate some meaningful progress towards this goal. However, P management challenges and opportunities in croplands vary widely among countries.


Assuntos
Produção Agrícola , Produtos Agrícolas , Fósforo , Desenvolvimento Sustentável , Produção Agrícola/métodos , Produção Agrícola/tendências , Produtos Agrícolas/classificação , Produtos Agrícolas/metabolismo , Fazendas , Nutrientes/metabolismo , Fósforo/metabolismo , Desenvolvimento Sustentável/tendências , Internacionalidade , Fatores Socioeconômicos , Bases de Dados Factuais
5.
J Anim Sci ; 100(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36082767

RESUMO

Thermal processing is used to produce most commercial pet foods and treats to improve safety, shelf life, nutritional characteristics, texture, and nutrient digestibility. However, heat treatments can degrade protein quality by damaging essential amino acids, as well as contribute to the Maillard reaction. The Maillard reaction forms melanoidins that favorably improve food qualities (e.g., color, flavor, aroma), but also form Maillard reaction products (MRP) and advanced glycation end-products that may negatively affect health. Because commercial pet diets are frequently fed to domestic cats and dogs throughout their lifetimes, it is critical to quantify MRP concentrations and understand the variables that influence their formation so future diets may be formulated with that in mind. Because few research studies on MRP in pet diets have been conducted, the goals of this study were to measure the MRP in commercial pet foods and treats, estimate pet MRP intake, and correlate MRP with dietary macronutrient concentrations. Fifty-three dry and wet dog foods, dog treats, and cat foods were analyzed for dry matter, organic matter, crude protein, acid-hydrolyzed fat, total dietary fiber, and gross energy using standard techniques. MRP were analyzed using high-performance liquid chromatography and gas chromatography-mass spectrometry. Data were analyzed using the Mixed Models procedure of SAS 9.4. Dry foods had lower reactive lysine concentrations and reactive lysine: total lysine ratios (indicator of damage) than wet foods. Wet foods had more fructoselysine (FRUC) than dry foods; however, dry dog treats contained more FRUC than wet dog treats. The greatest 5-hydroxymethyl-2-furfural (HMF) concentrations were measured in dry and wet dog foods, whereas the lowest HMF concentrations were measured in dry and wet cat foods. Based on dietary concentrations and estimated food intakes, dogs and cats fed wet foods are more likely to consume higher carboxymethyllysine and FRUC concentrations than those fed dry foods. However, dogs fed wet foods are more likely to consume higher HMF concentrations than those fed dry foods. In cats, those fed dry foods would consume higher HMF concentrations than those fed wet foods. We demonstrated that pet foods and treats contain highly variable MRP concentrations and depend on diet/treat type. In general, higher MRP concentrations were measured in wet pet foods and dry treats. While these findings are valuable, in vivo testing is needed to determine if and how MRP consumption affect pet health.


When heat is applied to food, the structure of sugars and proteins are rearranged. Some of the newly formed compounds are Maillard reaction products (MRP). The Maillard reaction can form melanoidins that improve color, flavor, and aroma, but can also lead to the loss of essential amino acids and the formation of advanced glycation end-products that may negatively affect animal health. Most commercial pet foods and treats are heated to improve safety, shelf life, nutritional characteristics, texture, and nutrient digestion, but MRP formation can be a problem. Because commercial pet foods are fed to domestic cats and dogs throughout their entire lives, quantifying MRP and understanding the variables that influence their formation is critical. The goals of this study were to determine the amount of MRP in commercial pet foods and treats, estimate MRP ingestion in pets, and correlate MRP with dietary macronutrient concentrations. Wet foods and dry treats contained more fructoselysine than dry foods, while dry foods contained more 5-hydroxymethyl-2-furfural. According to our findings, wet diets will result in higher total MRP, carboxymethyllysine, and fructoselysine intake than dry diets. While these findings are valuable, in vivo testing is needed to determine if and how MRP consumption affect pet health.


Assuntos
Doenças do Gato , Doenças do Cão , Gatos , Cães , Animais , Produtos Finais de Glicação Avançada , Ração Animal/análise , Lisina/análise , Nutrientes/metabolismo , Dieta/veterinária , Reação de Maillard , Furaldeído/análise , Digestão
6.
PLoS One ; 17(9): e0274076, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36112613

RESUMO

Genetic and environmental manipulations, such as dietary restriction, can improve both health span and lifespan in a wide range of organisms, including humans. Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when dietary restriction occurs in the lifecycle of the organism or the nature of the changes in nutrients. Due to the complexity of metabolic pathways and the diversity in outputs, the underlying mechanisms regulating diet-associated pro-longevity are not yet well understood. Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a dietary restriction model that is associated with lengthened lifespan and reproductive potential. To explore the metabolic pathways regulating ARD in greater depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. Focusing on the three phases of ARD (initiation, maintenance, and recovery), we found that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. Further investigation of downstream targets of NHR-49 suggest the transcription factor influences ARD initiation through the fatty acid ß-oxidation pathway. Consistent with these findings, our analysis revealed a change in levels of neutral lipids associated with ARD entry defects. Our findings identify conserved genetic pathways required for ARD entry and recovery and uncover genetic interactions that provide insight into the role of OGT and OGA.


Assuntos
Diapausa , Nutrientes , Transdução de Sinais , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Diapausa/genética , Diapausa/fisiologia , Ácidos Graxos/metabolismo , Glucosamina/metabolismo , Humanos , Insulinas/metabolismo , Lipídeos/química , Nutrientes/metabolismo , Nutrientes/farmacologia , Reprodução/genética , Reprodução/fisiologia , Transdução de Sinais/genética , Sirtuínas/genética , Sirtuínas/metabolismo , Fatores de Transcrição/metabolismo
7.
Life Sci Alliance ; 5(11)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36114003

RESUMO

Solute carrier (SLC) transporters control fluxes of nutrients and metabolites across membranes and thereby represent a critical interface between the microenvironment and cellular and subcellular metabolism. Because of substantial functional overlap, the interplay and relative contributions of SLCs in response to environmental stresses remain poorly elucidated. To infer functional relationships between SLCs and metabolites, we developed a strategy to identify SLCs able to sustain cell viability and proliferation under growth-limiting concentrations of essential nutrients. One-by-one depletion of 13 amino acids required for cell proliferation enabled gain-of-function genetic screens using a SLC-focused CRISPR/Cas9-based transcriptional activation approach to uncover transporters relieving cells from growth-limiting metabolic bottlenecks. Among the transporters identified, we characterized the cationic amino acid transporter SLC7A3 as a gene that, when up-regulated, overcame low availability of arginine and lysine by increasing their uptake, whereas SLC7A5 was able to sustain cellular fitness upon deprivation of several neutral amino acids. Moreover, we identified metabolic compensation mediated by the glutamate/aspartate transporters SLC1A2 and SLC1A3 under glutamine-limiting conditions. Overall, this gain-of-function approach using human cells uncovered functional transporter-nutrient relationships and revealed that transport activity up-regulation may be sufficient to overcome environmental metabolic restrictions.


Assuntos
Proteínas de Membrana Transportadoras , Nutrientes , Sistemas de Transporte de Aminoácidos Básicos/genética , Aminoácidos/metabolismo , Arginina/metabolismo , Ácido Aspártico/metabolismo , Mutação com Ganho de Função , Glutamatos/metabolismo , Glutamina/metabolismo , Humanos , Transportador 1 de Aminoácidos Neutros Grandes , Lisina/metabolismo , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Nutrientes/metabolismo
8.
Cancer Res ; 82(22): 4164-4178, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36084256

RESUMO

Exercise prevents cancer incidence and recurrence, yet the underlying mechanism behind this relationship remains mostly unknown. Here we report that exercise induces the metabolic reprogramming of internal organs that increases nutrient demand and protects against metastatic colonization by limiting nutrient availability to the tumor, generating an exercise-induced metabolic shield. Proteomic and ex vivo metabolic capacity analyses of murine internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active human subject plasma demonstrated increased carbohydrate utilization following exercise. Epidemiologic data from a 20-year prospective study of a large human cohort of initially cancer-free participants revealed that exercise prior to cancer initiation had a modest impact on cancer incidence in low metastatic stages but significantly reduced the likelihood of highly metastatic cancer. In three models of melanoma in mice, exercise prior to cancer injection significantly protected against metastases in distant organs. The protective effects of exercise were dependent on mTOR activity, and inhibition of the mTOR pathway with rapamycin treatment ex vivo reversed the exercise-induced metabolic shield. Under limited glucose conditions, active stroma consumed significantly more glucose at the expense of the tumor. Collectively, these data suggest a clash between the metabolic plasticity of cancer and exercise-induced metabolic reprogramming of the stroma, raising an opportunity to block metastasis by challenging the metabolic needs of the tumor. SIGNIFICANCE: Exercise protects against cancer progression and metastasis by inducing a high nutrient demand in internal organs, indicating that reducing nutrient availability to tumor cells represents a potential strategy to prevent metastasis. See related commentary by Zerhouni and Piskounova, p. 4124.


Assuntos
Exercício Físico , Melanoma , Nutrientes , Proteômica , Animais , Humanos , Camundongos , Glucose/metabolismo , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Estudos Prospectivos , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Exercício Físico/fisiologia , Nutrientes/genética , Nutrientes/metabolismo
9.
Environ Pollut ; 313: 120100, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36075333

RESUMO

As the only "tropical base of agricultural production" in China, Hainan lsland is vigorously developing high-value agriculture and is becoming the province with the highest proportion of cash crops. However, this intensive farming with large nutrient inputs has caused cropland degradation, nitrogen (N) and phosphorus (P) overloads and water pollution, which have been reversed to initiate the construction of free trade ports. Here, we systematically review the status, driving factors, and environmental impacts of cropland degradation and nutrient overload with quantified evaluations and compared with other global tropics. Over the last 30 years, the soil pH in Hainan decreased by 0.3 units, and the soil organic carbon (SOC) decreased by 20%. This soil degradation has consequently aggravated nutrient losses, caused low use efficiency, and has required farmers add additional large nutrient to maintain harvests. P overuse is more serious than N overuse in Hainan due to the misuse of high P content compound fertilizers. The current N and P usage densities were 4% and 66% higher than the national average per crop season, i.e., 301 kg N ha-1 and 98 kg P ha-1, respectively, and the application rates were even higher for vegetables, i.e., 43% and 115% higher than the national average for vegetables. Consequently, water quality degradation occurred. The nutrient contents of several estuaries have exceeded the Class III standards. Potential improvement strategies are proposed: (i) Organic materials must be recycled to curb the declines in SOC and pH, and more benefits would be obtained by together use of biochar. (ii) Nutrient quotas must be implemented to balance nutrient budgets and reduce excessive surpluses and losses. (iii) The service functions of ecological protection zones for water and soil conservation must be strengthened. These strategies also apply to other global tropics that face similar challenges of soil and ecological degradation.


Assuntos
Fertilizantes , Solo , Agricultura , Carbono , China , Produtos Agrícolas/química , Fertilizantes/análise , Nitrogênio/análise , Nutrientes/metabolismo , Fósforo/análise , Solo/química
10.
Pak J Biol Sci ; 25(8): 755-764, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36098202

RESUMO

<b>Background and Objective:</b> The inclusion of clay minerals in dairy nutrition is getting attention owing to their proven beneficial effects. The current study aimed to evaluate the effect of dietary supplementation of three different clay minerals (bentonite, zeolite and humic acid) on the performance of lactating Boer goats. <b>Materials and Methods:</b> Twenty lactating Boer goats (having an average body weight ~42.7 kg) were divided into four groups (5 animals each) by using a completely randomized design (CRD). Each group was fed with one of four dietary treatments: Control group with basal ration R1: Consisting of concentrate feed mixture (CFM) and clover hay (50:50%, C:R) on a dry matter (DM) basis, R2: Basal ration plus 1% bentonite, R3: Basal ration plus 1.25% zeolite and R4: Basal ration plus 0.5% humic acid. <b>Results:</b> The results revealed that bentonite and humic acid increased (p<0.05) the nutrient digestibility and nutritive values compared to zeolite and control groups. Ruminal ammonia and total volatile fatty acids (TVFAs) contents increased (p<0.05) with supplementation of bentonite. No effect of clays supplementation was observed on plasma total protein, urea and creatinine, however, it increased (p<0.05) the albumin concentration and albumin/globulin ratios compared to the control while decreasing the plasma globulin contents. Supplementation of humic acid increased (p<0.05) the AST concentrations. Bentonite supplementation recorded the highest milk yield (p<0.05) and composition, while the zeolite group had the lowest values. <b>Conclusion:</b> The present study indicated that the inclusion of clay minerals particularly bentonite (at 1%) can positively affect the performance of lactating Boer goats.


Assuntos
Rúmen , Zeolitas , Albuminas , Animais , Bentonita/metabolismo , Bentonita/farmacologia , Argila , Dieta/veterinária , Feminino , Fermentação , Cabras , Substâncias Húmicas , Lactação , Leite/metabolismo , Nutrientes/metabolismo , Rúmen/metabolismo , Zeolitas/metabolismo , Zeolitas/farmacologia
11.
J Anim Sci ; 100(10)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35950990

RESUMO

This study was to evaluate the effects of soy protein concentrate (SPC) supplementation replacing animal protein supplements on intestinal immune status, intestinal oxidative stress status, nutrient digestibility, mucosa-associated microbiota, and growth performance of nursery pigs. Thirty-two newly weaned pigs at 21 d of age with 6.4 ± 0.4 kg body weight (BW) were allotted to four treatments in a randomized complete block design with initial BW and sex as blocks. Pigs were fed for 35 d in three phases. Dietary treatments were SPC 0% (diets with fish meal 4/2/1%, poultry meal 10/8/4%, blood plasma 4/2/1%, and crude protein 24.6/22.6/20.9% for phase 1/2/3, respectively), SPC 33%, SPC 66%, and SPC 100% (SPC 0% diets with SPC replacing 33/66/100% of animal protein supplements, respectively). Pigs were euthanized on day 35 to collect jejunal mucosa and tissues to evaluate intestinal immune status, intestinal oxidative stress status, intestinal morphology, and mucosa-associated microbiota in the jejunum. Titanium dioxide was added in phase three diets as an indigestible marker. Ileal digesta was collected to measure apparent ileal digestibility (AID) of nutrients. Data were analyzed using MIXED and NLMIXED procedures of SAS. Increasing SPC supplementation by replacing animal protein supplements linearly decreased (P < 0.05) the BW, ADG, and ADFI of pigs during the overall period, and linearly increased (P < 0.05) peptide tyrosine tyrosine (PYY) in jejunum. Increasing SPC supplementation linearly decreased (P < 0.05) feed cost per weight gain. In the exponential model, SPC can replace animal protein supplements up to 10.5% and 16.5% without reducing the ADG and ADFI of pigs, respectively. The SPC 100% decreased (P < 0.05) Helicobacteraceae, Campylobacteraceae, alpha diversity, and changed beta diversity of microbiota in the jejunal mucosa. In conclusion, SPC supplementation replacing animal protein supplements reduced growth performance by reducing feed intake, which might be related to increased PYY. However, 10.5% and 16.8% of animal protein supplements can be replaced by SPC without affecting BW gain and feed intake of nursery pigs, respectively. Complete removal of animal protein supplements by SPC supplementation modulated the composition of jejunal mucosa-associated microbiota by reducing Helicobacteraceae and Campylobacteraceae, whereas without affecting the intestinal immune status, intestinal oxidative stress status, intestinal morphology, and AID of nutrients in nursery pigs.


Due to the high-quality nutrients and functional compounds, animal protein supplements are generally included in nursery pig diets to relieve the negative impacts caused by weaning stress. However, the high cost, short supply, and potential safety issues of animal protein supplements limit their use. Soybean meal is commonly used in swine diets due to the high nutritional values and competitive cost, however, antinutritional factors in soybean meal have been shown to impair the health and growth of nursery pigs. Soy protein concentrate is processed from soybean meal by ethanol extraction and efficiently removes the anti-nutritional factors. The aim of this study was to investigate the effects of soy protein concentrate replacing animal protein supplements at various levels on intestinal immune status, intestinal oxidative stress status, nutrient digestibility, and growth performance of nursery pigs. The use of soy protein concentrate completely replacing animal protein supplements showed benefits on modulating the bacterial ecosystem on the mucosal lining of the small intestine by decreasing potentially harmful bacteria, whereas without affecting intestinal immune status, intestinal oxidative stress status, intestinal morphology, and nutrient digestibility. However, excessive use of soy protein concentrate replacing animal protein supplements decreased the weight gain of nursery pigs due to reduced feed intake.


Assuntos
Microbiota , Proteínas de Soja , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Digestão , Mucosa Intestinal/metabolismo , Nutrientes/metabolismo , Estresse Oxidativo , Peptídeos/metabolismo , Proteínas de Soja/metabolismo , Suínos , Tirosina/metabolismo , Aumento de Peso
12.
Nature ; 608(7922): 374-380, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35831501

RESUMO

Food and water are rewarding in part because they satisfy our internal needs1,2. Dopaminergic neurons in the ventral tegmental area (VTA) are activated by gustatory rewards3-5, but how animals learn to associate these oral cues with the delayed physiological effects of ingestion is unknown. Here we show that individual dopaminergic neurons in the VTA respond to detection of nutrients or water at specific stages of ingestion. A major subset of dopaminergic neurons tracks changes in systemic hydration that occur tens of minutes after thirsty mice drink water, whereas different dopaminergic neurons respond to nutrients in the gastrointestinal tract. We show that information about fluid balance is transmitted to the VTA by a hypothalamic pathway and then re-routed to downstream circuits that track the oral, gastrointestinal and post-absorptive stages of ingestion. To investigate the function of these signals, we used a paradigm in which a fluid's oral and post-absorptive effects can be independently manipulated and temporally separated. We show that mice rapidly learn to prefer one fluid over another based solely on its rehydrating ability and that this post-ingestive learning is prevented if dopaminergic neurons in the VTA are selectively silenced after consumption. These findings reveal that the midbrain dopamine system contains subsystems that track different modalities and stages of ingestion, on timescales from seconds to tens of minutes, and that this information is used to drive learning about the consequences of ingestion.


Assuntos
Dopamina , Neurônios Dopaminérgicos , Hipotálamo , Vias Neurais , Nutrientes , Estado de Hidratação do Organismo , Área Tegmentar Ventral , Animais , Sinais (Psicologia) , Digestão , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Ingestão de Alimentos , Trato Gastrointestinal/metabolismo , Hipotálamo/citologia , Hipotálamo/fisiologia , Mesencéfalo/citologia , Mesencéfalo/fisiologia , Camundongos , Nutrientes/metabolismo , Estado de Hidratação do Organismo/efeitos dos fármacos , Recompensa , Fatores de Tempo , Área Tegmentar Ventral/citologia , Área Tegmentar Ventral/fisiologia , Água/metabolismo , Água/farmacologia , Equilíbrio Hidroeletrolítico
13.
Nature ; 607(7919): 610-616, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35831510

RESUMO

Mechanistic target of rapamycin complex 1 (mTORC1) controls growth by regulating anabolic and catabolic processes in response to environmental cues, including nutrients1,2. Amino acids signal to mTORC1 through the Rag GTPases, which are regulated by several protein complexes, including GATOR1 and GATOR2. GATOR2, which has five components (WDR24, MIOS, WDR59, SEH1L and SEC13), is required for amino acids to activate mTORC1 and interacts with the leucine and arginine sensors SESN2 and CASTOR1, respectively3-5. Despite this central role in nutrient sensing, GATOR2 remains mysterious as its subunit stoichiometry, biochemical function and structure are unknown. Here we used cryo-electron microscopy to determine the three-dimensional structure of the human GATOR2 complex. We found that GATOR2 adopts a large (1.1 MDa), two-fold symmetric, cage-like architecture, supported by an octagonal scaffold and decorated with eight pairs of WD40 ß-propellers. The scaffold contains two WDR24, four MIOS and two WDR59 subunits circularized via two distinct types of junction involving non-catalytic RING domains and α-solenoids. Integration of SEH1L and SEC13 into the scaffold through ß-propeller blade donation stabilizes the GATOR2 complex and reveals an evolutionary relationship to the nuclear pore and membrane-coating complexes6. The scaffold orients the WD40 ß-propeller dimers, which mediate interactions with SESN2, CASTOR1 and GATOR1. Our work reveals the structure of an essential component of the nutrient-sensing machinery and provides a foundation for understanding the function of GATOR2 within the mTORC1 pathway.


Assuntos
Aminoácidos , Microscopia Crioeletrônica , Complexos Multiproteicos , Nutrientes , Subunidades Proteicas , Aminoácidos/metabolismo , Arginina , Proteínas de Transporte , Humanos , Leucina , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Complexos Multiproteicos/ultraestrutura , Nutrientes/metabolismo , Domínios Proteicos , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Proteínas
14.
Nat Commun ; 13(1): 3544, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729093

RESUMO

Immunometabolism contributes to inflammation, but how activated macrophages acquire extracellular nutrients to fuel inflammation is largely unknown. Here, we show that the plasma membrane potential (Vm) of macrophages mediated by Kir2.1, an inwardly-rectifying K+ channel, is an important determinant of nutrient acquisition and subsequent metabolic reprogramming promoting inflammation. In the absence of Kir2.1 activity, depolarized macrophage Vm lead to a caloric restriction state by limiting nutrient uptake and concomitant adaptations in nutrient conservation inducing autophagy, AMPK (Adenosine 5'-monophosphate-activated protein kinase), and GCN2 (General control nonderepressible 2), which subsequently depletes epigenetic substrates feeding histone methylation at loci of a cluster of metabolism-responsive inflammatory genes, thereby suppressing their transcription. Kir2.1-mediated Vm supports nutrient uptake by facilitating cell-surface retention of nutrient transporters such as 4F2hc and GLUT1 by its modulation of plasma membrane phospholipid dynamics. Pharmacological targeting of Kir2.1 alleviated inflammation triggered by LPS or bacterial infection in a sepsis model and sterile inflammation in human samples. These findings identify an ionic control of macrophage activation and advance our understanding of the immunomodulatory properties of Vm that links nutrient inputs to inflammatory diseases.


Assuntos
Canais de Potássio Corretores do Fluxo de Internalização , Membrana Celular/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Potenciais da Membrana , Proteínas de Membrana Transportadoras/metabolismo , Nutrientes/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo
15.
J Dairy Sci ; 105(8): 6710-6723, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35717332

RESUMO

The objectives of this study were to examine the effects of pelleted starter diets differing in starch and neutral detergent fiber (NDF) content when fed differing levels of milk replacer (MR) on nutrient digestibility, whole gastrointestinal tract fermentation, pH, and inflammatory markers in dairy calves around weaning. Calves were randomly assigned to 1 of 4 dietary treatments (n = 12 per treatment) in a 2 × 2 factorial design based on daily MR allowance and amount of starch in pelleted starter (SPS): 0.691 kg of MR per day [dry matter (DM) basis] with starter containing low or high starch (12.0% and 35.6% starch on DM basis, respectively), and 1.382 kg of MR per day (DM) with starter containing low or high starch. All calves were housed in individual pens with straw bedding until wk 5 when bedding was covered. Calves were fed MR twice daily (0700 and 1700 h) containing 24.5% crude protein (DM) and 19.8% fat (DM), and had access to pelleted starter (increased by 50 g/d if there were no refusals before weaning and then 200 g/d during and after weaning) and water starting on d 1. Calves arrived between 1 and 3 d of age and were enrolled into an 8-wk study, with calves undergoing step-down weaning during wk 7. Starting on d 35, an indwelling pH logger was inserted orally to monitor rumen pH until calves were dissected at the end of the study in wk 8. Higher SPS calves showed an increase in rumen pH magnitude (1.46 ± 0.07) compared with low SPS calves (1.16 ± 0.07), a decrease in rumen pH in wk 8 (high SPS: 5.37 ± 0.12; low SPS: 5.57 ± 0.12), and a decrease in haptoglobin in wk 8 (high SPS: 0.24 ± 0.06 g/L; low SPS: 0.49 ± 0.06 g/L). The majority of differences came from increased starter intake in general, which suggests that with completely pelleted starters the differences in starch and NDF do not elicit drastic changes in fermentation, subsequent end products, and any resulting inflammation in calves around weaning.


Assuntos
Substitutos do Leite , Leite , Ração Animal/análise , Animais , Peso Corporal , Bovinos , Dieta/veterinária , Fibras na Dieta/metabolismo , Fermentação , Trato Gastrointestinal/metabolismo , Concentração de Íons de Hidrogênio , Leite/metabolismo , Nutrientes/metabolismo , Rúmen/metabolismo , Amido/metabolismo , Desmame
16.
Cell Rep ; 39(11): 110943, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35705052

RESUMO

The suppressive function of regulatory T (Treg) cells is tightly controlled by nutrient-fueled mechanistic target of rapamycin complex 1 (mTORC1) activation, yet its dynamics and negative regulation remain unclear. Here we show that Treg-specific depletion of vacuolar protein sorting 33B (Vps33B) in mice results in defective Treg cell suppressive function and acquisition of effector phenotype, which in turn leads to disturbed T cell homeostasis and boosted antitumor immunity. Mechanistically, Vps33B binds with lysosomal nutrient-sensing complex (LYNUS) and promotes late endosome and lysosome fusion and clearance of the LYNUS-containing late endosome/lysosome, and therefore suppresses mTORC1 activation. Vps33B deficiency in Treg cells results in disordered endosome lysosome fusion, which leads to accumulation of LYNUS that causes elevated mTORC1 activation and hyper-glycolytic metabolism. Taken together, our study reveals that Vps33B maintains Treg cell suppressive function through sustaining endolysosomal homeostasis and therefore restricting amino acid-licensed mTORC1 activation and metabolism.


Assuntos
Lisossomos , Alvo Mecanístico do Complexo 1 de Rapamicina , Linfócitos T Reguladores , Proteínas de Transporte Vesicular , Animais , Lisossomos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Nutrientes/metabolismo , Transporte Proteico , Linfócitos T Reguladores/metabolismo , Proteínas de Transporte Vesicular/metabolismo
17.
J Environ Manage ; 317: 115395, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35751241

RESUMO

Broadacre (arable) crops generally require a relatively higher nutrient input toward yield targets. The efficient use of nutrients in arable farmlands is very vital to this endeavor. It minimizes fertilizer input and adverse soil and environmental implications that may arise from the incremental use of fertilizers. It is understood that enhancing the natural capacity of the soil (i.e., the soil's physical, chemical, and biological quality), may effectively improve soil nutrient dynamics, availability, and efficient use by crops. The adoption of integrated nutrient management (INM) approaches such as the organic amendment of the soil in addition to fertilizer use has shown positive impacts on maintaining and recovering soil quality, hence lowering excessive fertilizer use in farmlands. Therefore, this review contextualized the effect of compost and fertilizer on nutrient use efficiency (NUE) and productivity of broadacre crops. The use of compost as an organic soil amendment material has shown some inherently unique advantages and beneficial impacts on soil health and fertility such as improved soil structure, nutrient retention, mobilization, and bioavailability. Several studies have explored these comparative advantages by either blending compost with chemical fertilizer before soil application or a co-application and have noted the observed amelioration of unfavorable soil conditions such as low porosity, high bulk density, low organic matter (OM), unfavorable pH, and cation exchange capacity (CEC), low biological activities with different doses of compost. Consequently, the co-utilization of composts and chemical fertilizers may become viable substitutes for chemical fertilizers in maintaining soil fertility, improving NUE, and crop yield in farmlands. The review further described the comparative environmental and economic implications of adopting the combined utilization of compost and fertilizers in farmlands.


Assuntos
Compostagem , Fertilizantes , Agricultura , Produtos Agrícolas/metabolismo , Fertilizantes/análise , Nitrogênio/análise , Nutrientes/metabolismo , Solo/química
18.
Nat Commun ; 13(1): 2706, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577788

RESUMO

In yeast, actin cables are F-actin bundles that are essential for cell division through their function as tracks for cargo movement from mother to daughter cell. Actin cables also affect yeast lifespan by promoting transport and inheritance of higher-functioning mitochondria to daughter cells. Here, we report that actin cable stability declines with age. Our genome-wide screen for genes that affect actin cable stability identified the open reading frame YKL075C. Deletion of YKL075C results in increases in actin cable stability and abundance, mitochondrial fitness, and replicative lifespan. Transcriptome analysis revealed a role for YKL075C in regulating branched-chain amino acid (BCAA) metabolism. Consistent with this, modulation of BCAA metabolism or decreasing leucine levels promotes actin cable stability and function in mitochondrial quality control. Our studies support a role for actin stability in yeast lifespan, and demonstrate that this process is controlled by BCAA and a previously uncharacterized ORF YKL075C, which we refer to as actin, aging and nutrient modulator protein 1 (AAN1).


Assuntos
Citoesqueleto de Actina , Longevidade , Mitocôndrias , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Longevidade/genética , Mitocôndrias/metabolismo , Nutrientes/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
19.
Trends Parasitol ; 38(8): 618-628, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35641406

RESUMO

The conserved plasmodial surface anion channel (PSAC) mediates nutrient uptake by bloodstream malaria parasites and is an antimalarial target. This pathogen-associated channel is linked to the clag multigene family, which is variably expanded in Plasmodium spp. Member genes are under complex epigenetic regulation, with the clag3 genes of the human P. falciparum pathogen exhibiting monoallelic transcription and mutually exclusive surface exposure on infected erythrocytes. While other multigene families use monoallelic expression to evade host immunity, the reasons of epigenetic control of clag genes are unclear. I consider existing models and their implications for nutrient acquisition and immune evasion. Understanding the reasons for epigenetic regulation of PSAC-mediated nutrient uptake will help clarify host-pathogen interactions and guide development of therapies resistant to allele switching.


Assuntos
Epigênese Genética , Malária Falciparum , Malária , Plasmodium falciparum , Plasmodium , Animais , Epigênese Genética/genética , Epigênese Genética/fisiologia , Eritrócitos/parasitologia , Humanos , Malária/parasitologia , Malária Falciparum/genética , Malária Falciparum/metabolismo , Nutrientes/metabolismo , Plasmodium/genética , Plasmodium/metabolismo , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo
20.
Commun Biol ; 5(1): 385, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35444215

RESUMO

The interaction between a cell and its environment shapes fundamental intracellular processes such as cellular metabolism. In most cases growth rate is treated as a proximal metric for understanding the cellular metabolic status. However, changes in growth rate might not reflect metabolic variations in individuals responding to environmental fluctuations. Here we use single-cell microfluidics-microscopy combined with transcriptomics, proteomics and mathematical modelling to quantify the accumulation of glucose within Escherichia coli cells. In contrast to the current consensus, we reveal that environmental conditions which are comparatively unfavourable for growth, where both nutrients and salinity are depleted, increase glucose accumulation rates in individual bacteria and population subsets. We find that these changes in metabolic function are underpinned by variations at the translational and posttranslational level but not at the transcriptional level and are not dictated by changes in cell size. The metabolic response-characteristics identified greatly advance our fundamental understanding of the interactions between bacteria and their environment and have important ramifications when investigating cellular processes where salinity plays an important role.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Bactérias/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Glucose/metabolismo , Humanos , Nutrientes/metabolismo
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