S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) link one-carbon metabolism to methylation status. However, it is unknown whether regulation of SAM and SAH by nutrient availability can be ...directly sensed to alter the kinetics of key histone methylation marks. We provide evidence that the status of methionine metabolism is sufficient to determine levels of histone methylation by modulating SAM and SAH. This dynamic interaction led to rapid changes in H3K4me3, altered gene transcription, provided feedback regulation to one-carbon metabolism, and could be fully recovered upon restoration of methionine. Modulation of methionine in diet led to changes in metabolism and histone methylation in the liver. In humans, methionine variability in fasting serum was commensurate with concentrations needed for these dynamics and could be partly explained by diet. Together these findings demonstrate that flux through methionine metabolism and the sensing of methionine availability may allow direct communication to the chromatin state in cells.
Display omitted
•Histone methylation dynamics occur in response to changes in SAM and SAH•Metabolism-regulated histone methylation affects gene expression•Diet alters methionine metabolism and histone methylation in the liver•Variation in human serum MET occurs at levels needed to alter histone methylation
Mentch et al. show that modulation of methionine metabolism, by altering nutrient availability, regulates SAM and SAH levels to drive specific histone methylation events that affect gene expression. Methionine cycle alterations can be sustained by diet in vivo and modulate histone methylation in the liver.
The Food and Agriculture Organization of the United Nations estimates that 843 million people worldwide are hungry and a greater number suffer from nutrient deficiencies. Approximately one billion ...people have inadequate protein intake. The challenge of preventing hunger and malnutrition will become even greater as the global population grows from the current 7.2 billion people to 9.6 billion by 2050. With increases in income, population, and demand for more nutrient‐dense foods, global meat production is projected to increase by 206 million tons per year during the next 35 years. These changes in population and dietary practices have led to a tremendous rise in the demand for food protein, especially animal‐source protein. Consuming the required amounts of protein is fundamental to human growth and health. Protein needs can be met through intakes of animal and plant‐source foods. Increased consumption of food proteins is associated with increased greenhouse gas emissions and overutilization of water. Consequently, concerns exist regarding impacts of agricultural production, processing and distribution of food protein on the environment, ecosystem, and sustainability. To address these challenging issues, the New York Academy of Sciences organized the conference “Frontiers in Agricultural Sustainability: Studying the Protein Supply Chain to Improve Dietary Quality” to explore sustainable innovations in food science and programming aimed at producing the required quality and quantity of protein through improved supply chains worldwide. This report provides an extensive discussion of these issues and summaries of the presentations from the conference.
Skeletal muscle is the largest metabolic organ system in the human body. As such, metabolic dysfunction occurring in skeletal muscle impacts whole-body nutrient homeostasis. Macronutrient metabolism ...changes within the skeletal muscle with aging, and these changes are associated in part with age-related skeletal muscle remodeling. Moreover, age-related changes in skeletal muscle metabolism are affected differentially between males and females and are likely driven by changes in sex hormones. Intrinsic and extrinsic factors impact observed age-related changes and sex-related differences in skeletal muscle metabolism. Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms. Understanding sex-specific aging skeletal muscle will assist with the development of therapies to attenuate adverse metabolic and functional outcomes.
Citrate lies at a critical node of metabolism, linking tricarboxylic acid metabolism and lipogenesis via acetyl-coenzyme A. Recent studies have observed that deficiency of the sodium-dependent ...citrate transporter (NaCT), encoded by SLC13A5, dysregulates hepatic metabolism and drives pediatric epilepsy. To examine how NaCT contributes to citrate metabolism in cells relevant to the pathophysiology of these diseases, we apply 13C isotope tracing to SLC13A5-deficient hepatocellular carcinoma (HCC) cells and primary rat cortical neurons. Exogenous citrate appreciably contributes to intermediary metabolism only under hypoxic conditions. In the absence of glutamine, citrate supplementation increases de novo lipogenesis and growth of HCC cells. Knockout of SLC13A5 in Huh7 cells compromises citrate uptake and catabolism. Citrate supplementation rescues Huh7 cell viability in response to glutamine deprivation or Zn2+ treatment, and NaCT deficiency mitigates these effects. Collectively, these findings demonstrate that NaCT-mediated citrate uptake is metabolically important under nutrient-limited conditions and may facilitate resistance to metal toxicity.
Display omitted
•HCC cells utilize NaCT-mediated citrate uptake for lipogenesis•Citrate import supports lipogenesis and anaplerosis upon glutamine deprivation•NaCT-mediated citrate uptake facilitates protection against zinc toxicity
Using isotope tracing, 13C MFA, and proliferation assays, Kumar et al. show that NaCT-mediated extracellular citrate is cytosolically catabolized, contributing to de novo lipogenesis (DNL) in HCC cells. Furthermore, extracellular citrate import by NaCT promotes growth in oxygen- and glutamine-limited conditions and protects against zinc-induced toxicity.
Dietary protein and amino acids are necessary for overall human health. Insufficient protein intake induces a negative protein balance with adverse outcomes such as muscle atrophy and functional ...decline—outcomes that are worsened in older adults. Furthermore, during inactivity, such as bed rest/hospitalization, skeletal muscle protein synthesis is reduced, protein balance is negative, and older adults lose significant amounts of muscle. Dietary protein and amino acid supplementation (∼30 g protein and ∼3 g leucine) stimulate skeletal muscle protein anabolism in healthy, community‐dwelling older adults and may be considered as possible nutritional interventions to improve the muscle protein balance and potentially support skeletal muscle maintenance in hospitalized older adults. The following is a timely review of metabolic and dietary challenges faced by hospitalized older adults and potential dietary protein and amino acids solutions for maintaining skeletal muscle health during hospitalization‐induced inactivity in this population.
Histidine is a nutritionally essential amino acid with many recognized benefits to human health, while circulating concentrations of histidine decline in pathologic conditions e.g., chronic ...obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). The purpose of this review is to examine the existing literature regarding the benefits of histidine intake, the adverse effects of excess histidine, and the upper tolerance level for histidine. Supplementation with doses of 4.0–4.5 g histidine/d and increased dietary histidine intake are associated with decreased BMI, adiposity, markers of glucose homeostasis (e.g., HOMA-IR, fasting blood glucose, 2-h postprandial blood glucose), proinflammatory cytokines, and oxidative stress. It is unclear from the limited number of studies in humans whether the improvements in glucoregulatory markers, inflammation, and oxidative stress are due to reduced BMI and adiposity, increased carnosine (a metabolic product of histidine with antioxidant effects), or both. Histidine intake also improves cognitive function (e.g., reduces appetite, anxiety, and stress responses and improves sleep) potentially through the metabolism of histidine to histamine; however, this relation is ambiguous in humans. At high intakes of histidine (>24 g/d), studies report adverse effects of histidine such as decreased serum zinc and cognitive impairment. There is limited research on the effects of histidine intake at doses between 4.5 and 24 g/d, and thus, a tolerable upper level has not been established. Determining tolerance to histidine supplementation has been limited by small sample sizes and, more important, a lack of a clear biomarker for histidine supplementation. The U-shaped curve of circulating zinc concentrations with histidine supplementation could be exploited as a relevant biomarker for supplemental histidine tolerance. Histidine is an important amino acid and may be necessary as a supplement in some populations; however, gaps in knowledge, which this review highlights, need to be addressed scientifically.
Activation of satellite cells and expansion of the muscle progenitor cell (MPC) population are essential to generate a sufficient number of cells to repair damaged skeletal muscle. Proliferating MPCs ...have high energetic and biosynthetic material requirements, and the ability to utilize oxidative phosphorylation (OXPHOS) and/or glycolysis may affect expansion capacity of MPCs. In the present study, we investigated the effect of donor age and sex on human (h)MPC expansion capacity and metabolic fuel preference. hMPCs from young and old male and female donors were grown for 408 h (17 days). Percent confluence, live nuclei count, and dead cell count were measured every 24 h. Metabolic phenotype was assessed by glucose uptake, expression of genes related to glycolysis and OXPHOS, and the Seahorse XF24 Phenotype Test Kit during the exponential phase of growth. hMPCs from old male donors had impaired expansion capacity secondary to heightened cell death early in expansion compared with hMPCs from young male donors, an effect not observed in female hMPCs. Age-related differences in metabolism were also sex dependent; markers of OXPHOS were altered in old (vs. young) male hMPCs, whereas markers of metabolism were largely unaffected by age in female hMPCs. For the first time, we identify sex-specific differences in cell death and OXPHOS that contribute to impaired expansion capacity of hMPC cell populations with age.
Histidine is an essential amino acid with health benefits that may warrant histidine supplementation; however, the clinical safety of histidine intake above the average dietary intake (1.52–5.20 g/d) ...needs to be vetted.
We aimed to determine the tolerance to graded dosages of histidine in a healthy adult population.
Healthy adults aged 21–50 y completed graded dosages of histidine supplement (4, 8, and 12 g/d, Study 1) (n = 20 men and n = 20 women) and/or a 16-g/d dosage of histidine (Study 2, n = 21 men and n = 19 women); 27 participants (n = 12 men and n = 15 women) completed both studies. After study enrollment and baseline measures, participants consumed encapsulated histidine for 4 wk followed by a 3-wk recovery period. Primary outcomes included vitals, select biochemical analytes, anthropometry, serum zinc, and body composition (via DXA).
No changes in vitals or body composition occurred with histidine supplementation in either study. Plasma histidine (measured in subjects who completed all dosages for Studies 1 and 2) was elevated at the 12- and 16-g/d dosages (compared with 0–8 g/d, P < 0.05) and blood urea nitrogen increased with dosage (P = 0.013) and time (P < 0.001) in Study 1 and with time in Study 2 (P < 0.001). In Study 1, mean ferritin concentrations were lower in 12 g/d (46.0 ng/mL; 95% CI: 34.8, 60.9 ng/mL) than in 4 g/d (51.6 ng/mL; 95% CI: 39.0, 68.4 ng/mL; P = 0.038). In Study 2, 16 g/d increased mean aspartate aminotransferase from baseline (19 U/L; 95% CI: 17, 22 U/L) to week 4 (24 U/L; 95% CI: 21, 27 U/L; P < 0.001) and mean serum zinc decreased from baseline (0.75 μg/dL; 95% CI: 0.71, 0.80 μg/dL) to week 4 (0.70 μg/dL; 95% CI: 0.66, 0.74 μg/dL; P = 0.011).
Although values remained within the normal reference ranges for all analytes measured, in all dosages tested, the human no-observed adverse effect level was determined to be 8 g/d owing to changes in blood parameters at the 12-g/d dosage. This trial was registered at clinicaltrials.gov as NCT04142294.
Physical function is the physical ability to fulfill one’s daily roles and responsibilities. Poor physical function is detrimental to health and income-generating activities. Unfortunately, there is ...a lack of validated methods to measure physical function in adult women in low- and middle-income countries, including Ethiopia, the locus of this study. This study evaluated the feasibility, reliability, and validity of physical tests, including the sit-to-stand (STS) and usual gait speed (UGS) and a context-appropriate instrumental activities of daily living (IADL) survey. The results of the STS were used to calculate a muscle quality index (MQI, STS accounting for body mass and leg length). Feasibility was ascertained qualitatively based on reports from the enumerators on their ability to administer the tests. Reliability was assessed by comparing the results of the tests and questions between each visit using either Cohen’s κ or Pearson’s ρ. The validity of MQI was assessed using relevant participant characteristics such as age and self-reported disability. The validity of the IADL was assessed using MQI. Study participants comprised 316 women between the ages of 18 and 45 years, living in rural Tigray, Ethiopia, who had previously participated in an impact evaluation of a safety net program. Over a one-week period, participants completed the STS and UGS tests and responded to the IADL survey questions three times. MQI was determined to be a feasible, reliable, and valid physical function test for women in rural, highland Ethiopia. UGS lacked feasibility and reliability; validity was not ascertained. The IADL questions were feasible and reliable, but validity was inconclusive. In rural Ethiopia, the MQI will be a valuable tool to develop interventions for improving physical function, which will have positive impacts on health and quality of life.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
