Chronic Administration of Exogenous Lactate Increases Energy Expenditure during Exercise through Activation of Skeletal Muscle Energy Utilization Capacity in Mice.

We compared the effects of chronic exogenous lactate and exercise training, which influence energy substrate utilization and body composition improvements at rest and during exercise, and investigated the availability of lactate as a metabolic regulator. The mice were divided into four groups: CON (sedentary + saline), LAC (sedentary + lactate), EXE (exercise + saline), and EXLA (exercise + lactate). The total experimental period was set at 4 weeks, the training intensity was set at 60-70% VO2max, and each exercise group was administered a solution immediately after exercise. Changes in the energy substrate utilization at rest and during exercise, the protein levels related to energy substrate utilization in skeletal muscles, and the body composition were measured. Lactate intake and exercise increased carbohydrate oxidation as a substrate during exercise, leading to an increased energy expenditure and increased protein levels of citrate synthase and malate dehydrogenase 2, key factors in the TCA(tricarboxylic acid) cycle of skeletal muscle. Exercise, but not lactate intake, induced the upregulation of the skeletal muscle glucose transport factor 4 and a reduction in body fat. Hence, chronic lactate administration, as a metabolic regulator, influenced energy substrate utilization by the skeletal muscle and increased energy expenditure during exercise through the activation of carbohydrate metabolism-related factors. Therefore, exogenous lactate holds potential as a metabolic regulator.

Inhibition of Crif1 protects fatty acid-induced POMC neuron-like cell-line damage by increasing CPT-1 function.

Hypothalamic proopiomelanocortin (POMC) neurons are sensors of signals that reflect the energy stored in the body. Inducing mild stress in proopiomelanocortin neurons protects them from the damage promoted by the consumption of a high-fat diet, mitigating the development of obesity; however, the cellular mechanisms behind these effects are unknown. Here, we induced mild stress in a proopiomelanocortin neuron cell line by inhibiting Crif1. In proopiomelanocortin neurons exposed to high levels of palmitate, the partial inhibition of Crif1 reverted the defects in mitochondrial respiration and ATP production; this was accompanied by improved mitochondrial fusion/fission cycling. Furthermore, the partial inhibition of Crif1 resulted in increased reactive oxygen species production, increased fatty acid oxidation, and reduced dependency on glucose for mitochondrial respiration. These changes were dependent on the activity of CPT-1. Thus, we identified a CPT-1-dependent metabolic shift toward greater utilization of fatty acids as substrates for respiration as the mechanism behind the protective effect of mild stress against palmitate-induced damage of proopiomelanocortin neurons.NEW & NOTEWORTHY Saturated fats can damage hypothalamic neurons resulting in positive energy balance, and this is mitigated by mild cellular stress; however, the mechanisms behind this protective effect are unknown. Using a proopiomelanocortin cell line, we show that under exposure to a high concentration of palmitate, the partial inhibition of the mitochondrial protein Crif1 results in protection due to a metabolic shift warranted by the increased expression and activity of the mitochondrial fatty acid transporter CPT-1.

Obesity-Resistant Mice on a High-Fat Diet Display a Distinct Phenotype Linked to Enhanced Lipid Metabolism.

Individually, metabolic variations can significantly influence predisposition to obesity in the form of the obesity-prone (super-responders) and obesity-resistant (non-responders) phenotypes in response to modern calorie-dense diets. In this study, C57BL/6J mice (n = 76) were randomly assigned to either a low-fat diet (LFD) or a high-fat diet (HFD) for 6 weeks, followed by selection of the normally obese (HFD), non-responders (NR), super-responders (SR), or super-responders switched back to the low-fat diet (SR-LFD) for an additional 8 weeks. SR mice showed the highest gains in body weight, lean and fat body mass, and total and free water, in part due to increased feed efficiency, despite having a respiratory exchange ratio (RER) similar to that of NR mice. A switch to the LFD was sufficient to revert most of the observed physiological changes in the SR-LFD mice; however, voluntary physical activity and exercise capacity did not return to the basal level. NR mice showed the highest food intake, lowest feed efficiency, increased oxygen consumption during the light (rest) cycle, increased physical activity during the dark (active) cycle, and increased heat production during both cycles. These variations were observed in the absence of changes in food intake and fecal parameters; however, NR fecal lipid content was lower, and the NR fecal microbiome profile was characterized by reduced abundance of Actinobacteria. Taken together, our findings suggest that NR mice showed an increased ability to metabolize excessive dietary fats in skeletal muscle at the expense of reduced exercise capacity that persisted for the duration of the study. These findings underscore the need for further comprehensive investigations into the mechanisms of obesity resistance, as they hold potential implications for weight-loss strategies in human subjects.

Effects of pemafibrate on left ventricular diastolic function in patients with type 2 diabetes mellitus: a pilot study.

Aims/introduction: Diabetic cardiomyopathy (DCM) is characterized predominantly by diastolic dysfunction. The multiple mechanisms underlying DCM include altered energy substrate utilization. Recent studies indicate that PPARα plays an important role in the pathogenesis of lipotoxic cardiomyopathy. Pemafibrate is known to be a selective PPARα modulator (SPPARMα). We thus investigated the effects of pemafibrate on cardiac diastolic function in patients with type 2 diabetes. Materials and methods: Seventeen patients with type 2 diabetes (T2D) and hypertriglyceridemia were screened and treated with pemafibrate at a dose of 0.2 mg/day for 8-16 weeks. Fourteen patients were eligible for analysis. Echocardiography was used for assessment of diastolic function. Early diastolic filling velocity (E), late atrial filling velocity (A) and the E/A ratio were included in this study. Peak early diastolic annular velocities (e') were also assessed using color tissue Doppler images. The primary endpoints were changes in the ratio of E to A (E/A), e', and the ratio of E to e' (E/e') from baseline. Results: Pemafibrate significantly increased average e' (7.24 ± 0.58 vs 7.94 ± 0.67, p = 0.019) and a significant reduction in E/e' (9.01 ± 0.94 vs 8.20 ± 0.91, p = 0.041). The increase in e' was significantly related to increases in fasting blood glucose (r = 0.607, p = 0.021) and non-esterified fatty acid (r = 0.592, p = 0.026). Conclusion: Pemafibrate improved diastolic function in patients with T2D and hypertriglyceridemia, suggesting that PPARα activation by pemafibrate prevents the development of DCM at an early stage.

Empagliflozin reduces podocyte lipotoxicity in experimental Alport syndrome.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are anti-hyperglycemic agents that prevent glucose reabsorption in proximal tubular cells. SGLT2i improves renal outcomes in both diabetic and non-diabetic patients, indicating it may have beneficial effects beyond glycemic control. Here, we demonstrate that SGLT2i affects energy metabolism and podocyte lipotoxicity in experimental Alport syndrome (AS). In vitro, we found that the SGLT2 protein was expressed in human and mouse podocytes to a similar extent in tubular cells. Newly established immortalized podocytes from Col4a3 knockout mice (AS podocytes) accumulate lipid droplets along with increased apoptosis when compared to wild-type podocytes. Treatment with SGLT2i empagliflozin reduces lipid droplet accumulation and apoptosis in AS podocytes. Empagliflozin inhibits the utilization of glucose/pyruvate as a metabolic substrate in AS podocytes but not in AS tubular cells. In vivo, we demonstrate that empagliflozin reduces albuminuria and prolongs the survival of AS mice. Empagliflozin-treated AS mice show decreased serum blood urea nitrogen and creatinine levels in association with reduced triglyceride and cholesterol ester content in kidney cortices when compared to AS mice. Lipid accumulation in kidney cortices correlates with a decline in renal function. In summary, empagliflozin reduces podocyte lipotoxicity and improves kidney function in experimental AS in association with the energy substrates switch from glucose to fatty acids in podocytes.

The thermal dependence of the protein-sparing effect in rainbow trout (Oncorhynchus mykiss, Walbaum 1792).

The authors performed an instantaneous bioenergetic study with rainbow trout (Oncorhynchus mykiss) of 206.3 g ± 2.9 g in a group respirometer of nine 250 l tanks at five different water temperatures (12, 14, 16, 18, 20°C) to determine the optimal thermal condition for a maximal visualization of the protein-sparing effect. Twelve fish per tank were tested at a stocking density of 9.94 kg m-3 ± 0.14 kg m-3 and fed three low-protein/high-energy diets with constant crude protein content of c. 35% and three different energy contents (17.35, 18.76, 20.50 MJ kg-1 ) once daily at a ration of 1.3% body weight (n = 3). Energy levels were increased by adding gelatinized wheat starch as a carbohydrate source and fish oil, canola oil and palmitin as lipid sources. Three different dietary digestible protein/digestible energy ratios (DP/DE: 20.38, 19.08, 18.09 mg kJ-1 ) were achieved by replacing bentonite as a non-nutritive filler with carbohydrates and lipids. Oxygen consumption and ammonia excretion were assessed to obtain the potentially retainable energy (RE) and ammonia quotient (AQ) as benchmarks for potential growth and protein-sparing effect. The results showed the lowest relative metabolic combustion of protein at 16.9°C ± 0.1°C. The authors determined this temperature to set the optimal thermal condition for the induction of a maximum protein-sparing effect in juvenile rainbow trout. Increasing the DP/DE ratio significantly altered the magnitude of the relative metabolic protein use but had no effect on its interactions with temperature. The authors were able to reduce average metabolic fuel use of protein across diets from 16.2% ± 2.3% at 12°C to 8.0% ± 1.2% at 16°C. This study found no relevant significant differences of RE with the environmental temperature.

Data on cardiac and vascular functionality in ex vivo and in vivo models following acute administration of trimethylamine N-oxide.

This dataset describes in detail the outcomes of acute trimethylamine N-oxide (TMAO) administration on cardiac, vascular and mitochondrial functionality in ex vivo and in vivo models. The accumulation of TMAO in target tissues was assessed after performing heart perfusion or by incubating aortic tissue in a solution containing TMAO. To evaluate the impact of TMAO on mitochondrial function, the aortic rings and heart homogenates of Wistar rats were incubated in a solution containing [9,10-3H] palmitate (5 µCi/ml) or D-[U-14C] glucose (0.625 µCi/ml) in the presence or absence of TMAO with subsequent measurement of substrate oxidation and uptake. The effects of TMAO on the vascular reactivity of isolated conductance and resistance vessels were tested by measuring their response to acetylcholine and sodium nitroprusside. The impact of elevated TMAO levels on cardiac function and infarct size caused by ischemia-reperfusion injury was evaluated in Langendorff perfused heart model. Normal and forced heart functioning was analyzed by echocardiography in CD-1 mouse acute cardiac stress model induced by isoproterenol (10 µg/mouse) upon single and 7 repeated daily administrations of TMAO (120 mg/kg). The data presented in the manuscript provide valuable information on measurements performed under conditions of acutely elevated TMAO levels in experimental models of cardiac and vascular function and energy metabolism. Furthermore, the data have high reuse potential as they could be applied in the planning of future in vitro, ex vivo, and in vivo studies addressing the molecular mechanisms targeted by elevated levels of TMAO.

Are Early Embryo Cleavage Kinetics Affected by Energy Substrates in Different Culture Media?

OBJECTIVE: This study aimed to investigate the influence of different culture media on early embryonic cleavage kinetics using time-lapse analysis and to determine the possible relationships between energy substrates in culture media and the cleavage kinetics. METHODS: A total of 10 021 embryos from 1310 couples were cultured in time-lapse incubators. Embryos cultured in Vitrolife media were allocated to group I, and those in COOK media to group II. Embryo cleavage time points up to the 8-cell stage (t2-t8) were observed after pronuclei fading. RESULTS: The baseline demographic features, in vitro fertilization indications, ovarian stimulation protocol, oocyte-cumulus complexes, fertilization rate, together with pregnancy and perinatal outcomes were similar (P>0.05) between groups I and II. According to the time-lapse analysis, all embryos in group I showed significantly faster cleavage speed than those in group II (P<0.05). Furthermore, there was better synchrony in division (s3) and a longer length of the third cell cycle duration (cc3) in group II. Interestingly, implanted embryos in group II showed faster cleavage speed than those in group I, especially at t4 and t7. The glucose contents and multiple major amino acids were similar between the two groups. Lactic and pyruvic acid contents were generally higher in group I than those in group II. CONCLUSION: Because different commercial culture media may influence cleavage kinetics of embryos, it is essential for embryologists to take culture media into consideration in selecting a potential embryo when using a time-lapse system before implantation.

Energy substrate metabolism and oxidative stress in metabolic cardiomyopathy.

Metabolic cardiomyopathy is an emerging cause of heart failure in patients with obesity, insulin resistance, and diabetes. It is characterized by impaired myocardial metabolic flexibility, intramyocardial triglyceride accumulation, and lipotoxic damage in association with structural and functional alterations of the heart, unrelated to hypertension, coronary artery disease, and other cardiovascular diseases. Oxidative stress plays an important role in the development and progression of metabolic cardiomyopathy. Mitochondria are the most significant sources of reactive oxygen species (ROS) in cardiomyocytes. Disturbances in myocardial substrate metabolism induce mitochondrial adaptation and dysfunction, manifested as a mismatch between mitochondrial fatty acid oxidation and the electron transport chain (ETC) activity, which facilitates ROS production within the ETC components. In addition, non-ETC sources of mitochondrial ROS, such as ß-oxidation of fatty acids, may also produce a considerable quantity of ROS in metabolic cardiomyopathy. Augmented ROS production in cardiomyocytes can induce a variety of effects, including the programming of myocardial energy substrate metabolism, modulation of metabolic inflammation, redox modification of ion channels and transporters, and cardiomyocyte apoptosis, ultimately leading to the structural and functional alterations of the heart. Based on the above mechanistic views, the present review summarizes the current understanding of the mechanisms underlying metabolic cardiomyopathy, focusing on the role of oxidative stress.

Corrigendum: Lactate and Myocardiac Energy Metabolism.

[This corrects the article DOI: 10.3389/fphys.2021.715081.].

The blood lactate/pyruvate equilibrium affair.

The Lactate Shuttle hypothesis is supported by a variety of techniques including mass spectrometry analytics following infusion of carbon-labeled isotopic tracers. However, there has been controversy over whether lactate tracers measure lactate (L) or pyruvate (P) turnover. Here, we review the analytical errors, use of inappropriate tissue and animal models, failure to consider L and P pool sizes in modeling results, inappropriate tracer and blood sampling sites, and failure to anticipate roles of heart and lung parenchyma on L⇔P interactions. With support from magnetic resonance spectroscopy (MRS) and immunocytochemistry, we conclude that carbon-labeled lactate tracers can be used to quantitate lactate fluxes.

Lactate and Myocardiac Energy Metabolism.

The myocardium is capable of utilizing different energy substrates, which is referred to as "metabolic flexibility." This process assures ATP production from fatty acids, glucose, lactate, amino acids, and ketones, in the face of varying metabolic contexts. In the normal physiological state, the oxidation of fatty acids contributes to approximately 60% of energy required, and the oxidation of other substrates provides the rest. The accumulation of lactate in ischemic and hypoxic tissues has traditionally be considered as a by-product, and of little utility. However, recent evidence suggests that lactate may represent an important fuel for the myocardium during exercise or myocadiac stress. This new paradigm drives increasing interest in understanding its role in cardiac metabolism under both physiological and pathological conditions. In recent years, blood lactate has been regarded as a signal of stress in cardiac disease, linking to prognosis in patients with myocardial ischemia or heart failure. In this review, we discuss the importance of lactate as an energy source and its relevance to the progression and management of heart diseases.

Effect of electromyostimulation on intramyocellular lipids of the vastus lateralis in older adults: a randomized controlled trial.

BACKGROUND: Excessive intramyocellular lipid (IMCL) accumulation is a primary cause of skeletal muscle insulin resistance, especially in older adults, and interventions that reduce IMCL contents are important to improve insulin sensitivity. Electromyostimulation (EMS)-induced changes in IMCL content in older adults remain unknown. The purpose of this study was to clarify the effects of a single bout of EMS on the IMCL content of the vastus lateralis muscle in older adults. METHODS: Twenty-two physically active, non-obese older men and women were randomly assigned to an EMS intervention group (69.0 ± 5.2 years, n = 12) or a control group (68.4 ± 3.5 years, n = 10). EMS was applied to the vastus lateralis (7 s on and 7 s off) for 30 min; control participants sat quietly for 30 min. IMCL content within the vastus lateralis was quantified with 1H-magnetic resonance spectroscopy (n = 7 per group). Fasting plasma glucose and insulin values were determined from blood samples collected before and after the EMS intervention. RESULTS: EMS induced a significant reduction in plasma glucose (93.1 ± 9.6 to 89.5 ± 9.1 mg/dL, p < 0.01), but not IMCL content (15.7 ± 15.7 to 15.8 ± 13.1 mmol/kg wet weight, p = 0.49) or insulin (5.4 ± 2.4 to 4.7 ± 2.7 µIU/mL, p = 0.18). In the control group, no changes in IMCL content in the vastus lateralis was observed after prolonged quiet sitting. CONCLUSION: EMS intervention for 30 min induces changes in plasma glucose, but no changes in IMCL content in older adults. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center ID: UMIN000020126 . Retrospectively registered on December 222,015. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023242.

The effects of metabolic substrates glucose, pyruvate, and lactate added to a skim milk-based semen extender for cooled storage of stallion sperm.

Under in vitro conditions, stallion sperm might preferentially use energy substrates that primarily undergo mitochondrial metabolism. The present study sought to determine the effects of glucose, pyruvate, lactate, or their combinations on the quality of stallion sperm subjected to cooled storage at different temperatures, when using a skim milk-based semen extender. In Experiment 1, no substrate (Control), glucose (40 mM; Glu-40), pyruvate (2 mM, 19.8 mM; Pyr-2, Pyr-19), lactate (2 mM, 19.8 mM; Lac-2, Lac-19, respectively), or their combinations (G/P/L-2 or G/P/L-19, respectively) were added to a milk-based extender and their effects were determined on motion characteristics, viability/acrosomal intactness (VAI), lipid peroxidation status (VLPP), and DNA integrity (COMPα-t) of sperm incubated for 1 h at 37 °C, or sperm stored for 24 h at either 10 or 20 °C. At any period and temperature tested, Glu-40, G/P/L-2, and G/P-L-19 resulted in similar motion characteristics (P > 0.05) but were higher than that of other treatment groups (P < 0.05). Mean VAI was highest in Glu-40 (P < 0.05). Mean VLPP was highest in G/P/L-2 and G/P/L-19 groups (P < 0.05), and mean COMPα-t was lowest in Control, Glu-40, G/P/L-2 and G/P/L-19 groups (P < 0.05). All measures of sperm quality were higher in semen stored at 10 °C than 20 °C (P < 0.05). In Experiment 2, increasing concentrations of either pyruvate or lactate (Pyr-40, Lac-40 or Pyr-80, Lac-80) were added to the extender as energy substrates and compared to glucose (40 mM), following storage for 72 h at either 10 or 20 °C. Groups Glu-40 and Pyr-40 yielded similar sperm motion characteristics and VAI, while VLPP and COMPα-t were reduced in these treatment groups, as compared to Pyr-80, Lac-40, and Lac-80 (P < 0.05). All measures of sperm quality were higher in semen stored at 10 °C vs 20 °C (P < 0.05). This study demonstrates that at storage temperatures of 10 or 20 °C, stallion sperm quality is optimized by the presence of glucose in a skim milk-based semen extender. The addition of substrates that readily support oxidative phosphorylation (i.e., pyruvate or lactate) did not improve the quality of stallion sperm over that of glucose alone and resulted in deleterious effects on sperm quality over time. These effects appeared to be associated with oxidative stress. Use of pyruvate (40 mM) as an alternative energy substrate to glucose generally yielded similar results to that of glucose when sperm were stored at 10 °C only.

Dietary Energy Partition: The Central Role of Glucose.

Humans have developed effective survival mechanisms under conditions of nutrient (and energy) scarcity. Nevertheless, today, most humans face a quite different situation: excess of nutrients, especially those high in amino-nitrogen and energy (largely fat). The lack of mechanisms to prevent energy overload and the effective persistence of the mechanisms hoarding key nutrients such as amino acids has resulted in deep disorders of substrate handling. There is too often a massive untreatable accumulation of body fat in the presence of severe metabolic disorders of energy utilization and disposal, which become chronic and go much beyond the most obvious problems: diabetes, circulatory, renal and nervous disorders included loosely within the metabolic syndrome. We lack basic knowledge on diet nutrient dynamics at the tissue-cell metabolism level, and this adds to widely used medical procedures lacking sufficient scientific support, with limited or nil success. In the present longitudinal analysis of the fate of dietary nutrients, we have focused on glucose as an example of a largely unknown entity. Even most studies on hyper-energetic diets or their later consequences tend to ignore the critical role of carbohydrate (and nitrogen disposal) as (probably) the two main factors affecting the substrate partition and metabolism.

The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review.

Exercise is an effective strategy for preventing and treating obesity and its related cardiometabolic disorders, resulting in significant loss of body fat mass, white adipose tissue browning, redistribution of energy substrates, optimization of global energy expenditure, enhancement of hypothalamic circuits that control appetite-satiety and energy expenditure, and decreased systemic inflammation and insulin resistance. Novel exercise-inducible soluble factors, including myokines, hepatokines, and osteokines, and immune cytokines and adipokines are hypothesized to play an important role in the body's response to exercise. To our knowledge, no review has provided a comprehensive integrative overview of these novel molecular players and the mechanisms involved in the redistribution of metabolic fuel during and after exercise, the loss of weight and fat mass, and reduced inflammation. In this review, we explain the potential role of these exercise-inducible factors, namely myokines, such as irisin, IL-6, IL-15, METRNL, BAIBA, and myostatin, and hepatokines, in particular selenoprotein P, fetuin A, FGF21, ANGPTL4, and follistatin. We also describe the function of osteokines, specifically osteocalcin, and of adipokines such as leptin, adiponectin, and resistin. We also emphasize an integrative overview of the pleiotropic mechanisms, the metabolic pathways, and the inter-organ crosstalk involved in energy expenditure, fat mass loss, reduced inflammation, and healthy weight induced by exercise.

In ovo injection with glycerol and insulin-like growth factor (IGF-I): hatchability, intestinal morphometry, performance, and carcass characteristics of broilers.

The objective of this study was to evaluate the effects of in ovo injection with glycerol (GLY) and insulin-like growth factor (IGF-I) on hatchability, biochemical parameters, intestinal morphometry, performance, and carcass characteristics of broiler chickens. A total of 400 fertilised eggs were distributed into five experimental groups. The treatments were arranged as non-injected (control), saline solution injected (0.9% NaCl solution), GLY solution injected (10 nmol/ml), IGF-I solution injected (100 ng/ml), and GLY + IGF-I solution injected. At 17.5 d of incubation, 0.5 ml of each solution was injected into the amniotic fluid of each egg of the injected groups. The injection of different solutions did not influence the hatchability and incubation time of the eggs. Compared to intact eggs, IGF-I and IGF-I+ GLY increased (p < 0.01) the blood IGF-I at hatching. Higher hepatic glycogen was observed (p < 0.05) with GLY or IGF-I. The tested substances decreased (p = 0.02) the fructose 1,6-biphosfate phosphatase activity but did not affect glycaemia. No difference in performance was observed in the first week. Higher feed intake and weight gain with lower feed conversion ratio was obtained ( p  < 0.05) with IGF-I at 14 d. At 21 d, higher weight gain was obtained (p = 0.05) with IGF-I, GLY, IGF-I, and GLY + IGF-I, resulting (p < 0.01) in birds with greater weight gain at 35 and 42 d of age. GLY provided higher villus height in the ileum at hatching and at 7 d of age. The tested solutions increased the relative weight of the liver at hatching. At 42 d of age, no carcass characteristics were influenced. It is concluded that GLY and IGF-I, together or separately, can be used in the in ovo feeding to improve the post-hatch performance of broilers, without affecting hatchability and carcass composition.

Lactate as a fulcrum of metabolism.

Mistakenly thought to be the consequence of oxygen lack in contracting skeletal muscle we now know that the L-enantiomer of the lactate anion is formed under fully aerobic conditions and is utilized continuously in diverse cells, tissues, organs and at the whole-body level. By shuttling between producer (driver) and consumer (recipient) cells lactate fulfills at least three purposes: 1] a major energy source for mitochondrial respiration; 2] the major gluconeogenic precursor; and 3] a signaling molecule. Working by mass action, cell redox regulation, allosteric binding, and reprogramming of chromatin by lactylation of lysine residues on histones, lactate has major influences in energy substrate partitioning. The physiological range of tissue [lactate] is 0.5-20 mM and the cellular Lactate/Pyruvate ratio (L/P) can range from 10 to >500; these changes during exercise and other stress-strain responses dwarf other metabolic signals in magnitude and span. Hence, lactate dynamics have rapid and major short- and long-term effects on cell redox and other control systems. By inhibiting lipolysis in adipose via HCAR-1, and muscle mitochondrial fatty acid uptake via malonyl-CoA and CPT1, lactate controls energy substrate partitioning. Repeated lactate exposure from regular exercise results in major effects on the expression of regulatory enzymes of glycolysis and mitochondrial respiration. Lactate is the fulcrum of metabolic regulation in vivo.

Effects of Different Energy Substrates and Nickel and Cadmium Ions on the Growth of Acidithiobacillus ferrooxidans and Its Application for Disposal of Ni-Cd Batteries.

In the present work, the effects of different energy substrates and nickel ions (Ni2+) and cadmium ions (Cd2+) on the growth of Acidithiobacillus ferrooxidans (A. ferrooxidans) were investigated. Ferrous sulphate (FeSO4) was the optimum energy substrate for A. ferrooxidans growth, among the selected substrates. When cultured together with FeSO4 and sulphur (S), A. ferrooxidans first oxidised the ferrous ions (Fe2+), and the S was utilised as the concentration of Fe2+ decreased. After adapting to culture with Ni2+ and Cd2+, A. ferrooxidans presented good tolerance to both ions, with the maximum concentration reaching 4.11 g/L Ni2+ and 1.69 g/L Cd2+. A preliminary simulation of industrial application was also performed on used Ni-Cd batteries. With bioleaching, the highest concentrations of Cd2+ and Ni2+ were 3003 mg/L at day 8 and 1863 mg/L at day 14, respectively.

Molecular ecological network reveals the response of metallurgical microorganisms to energy substrates / 生物工程学报

By analyzing the shift of microbial communities under different iron/sulfur ratios, the response of metallurgical microorganisms to energy substrates was investigated based on molecular ecological networks. High-throughput sequencing of microbial samples from different domesticated batches was conducted to analyze the changes in community composition, alpha and beta diversity. Based on the molecular ecological network, the interactions between microorganisms under different iron/sulfur ratios were explored. Keystones were identified to analyze the community response to energy substrates. In the process of domestication based on different energy substrates, the dominant species in the in iron-rich and sulfur-less community were Acidithiobacillus ferrooxidans and A. ferriphilus. A. thiooxidans accounted for up to 90% in the sulfur-rich and iron-less community after 3 domesticating batches. The results of alpha and beta diversity analysis show that the domestication process of sulfur-rich and iron-less substrates reduced the diversity of microbial communities. Molecular ecological network analysis shows that the keystones were all rare species with low abundance. During the domestication by sulfur-rich and iron-less energy substrates, the bacterial species had a closer symbiotic relationship and the community was more stable. Through this domestication experiment, the impact of different energy substrates on microbial aggregation was clarified. Domesticating metallurgical microorganisms by using sulfur-rich and iron-less energy substrates made the microbial colonies to be more stable, which was conducive to the oxidation of iron and sulfur, promoting the dissolution of sulfide minerals. Our findings provide a reference for the directional domestication of metallurgical microorganisms.