Metabolic Technologies (United States)

β-Hydroxy-β-methylbutyrate (HMB), a metabolite of leucine, increases both protein synthesis and lipolysis, immune function, and overall health in both humans and animals. Previous cattle studies have shown that HMB, fed as calcium HMB (CaHMB), can minimize stress responses and improve meat quality. The objective of the present study was to investigate the effect of feeding CaHMB in a subtropical feedlot on performance of Nellore (Bos indicus) bulls. A total of 3,520 bulls (64 pens; 55 animals per pen) were studied with four levels of CaHMB (0 [control, CON], 3, 5, or 7 g per head per day) and half the pens had shade access (SH), and half did not in a split-plot experimental design. Diets containing CaHMB were fed during three phases of the study, adaptation, growth, and finishing. There were no CaHMB × SH interactions observed for any variable measured. However, adjusted final body weight (FBW) tended to increase in CaHMB-treated bulls up to 5.8 kg in bulls fed 3 g per day (linear P < 0.07). Additionally, adjusted average daily gain (ADG) and carcass ADG were also increased with 3 g per day CaHMB by 3.2% and 2.6%, respectively, when compared with CON (linear P < 0.04). Bulls fed CaHMB tended to have increased hot carcass weight (HCW) by up to 3.4 kg in bulls fed 3 g CaHMB per day and a 0.36% increase in dressing percentage (DP) (linear P < 0.07 and 0.09, respectively). No differences were observed in dry matter intake (DMI) during any of the feeding periods. No significant differences were observed in gain:feed. Of major importance to the subtropical environment, 34% of the days were considered hot to very hot with the comfort level (InCI) >0.45 on a 0 to 1.0 scale. In conclusion, supplementing Bos indicus bulls with CaHMB resulted in improved growth performance and carcass yield.

Inflammation is associated with the formation of reactive oxygen species (ROS) and the formation of lipid-derived compounds, such as isolevuglandins (IsoLGs), malondialdehyde, 4-hydroxy-nonenal, and 4-oxo-nonenal. The most reactive of these are the IsoLGs, which form covalent adducts with lysine residues and other cellular primary amines leading to changes in protein function, immunogenicity, and epigenetic alterations and have been shown to contribute to a number of inflammatory diseases. 2-Hydroxybenzylamine (2-HOBA) is a natural compound found in buckwheat seeds and reacts with all IsoLG adducts preventing adduct formation with proteins and DNA. Therefore, 2-HOBA is well positioned as an agent for the prevention of inflammatory-prone diseases. In this study, we examined the potential beneficial effects of 2-HOBA on oxidative stress and inflammatory biomarkers in two cohorts of healthy younger and older adults. We utilized the Olink® targeted inflammation panel before and after an oral 15-day treatment regimen with 2-HOBA. We found significant relative changes in the plasma concentration of 15 immune proteins that may reflect the in vivo immune targets of 2-HOBA. Treatment of 2-HOBA resulted in significant increased levels of CCL19, IL-12β, IL-20Rα, and TNFβ, whereas levels of TWEAK significantly decreased. Ingenuity Pathway Analysis identified canonical pathways regulated by the differentially secreted cytokines, chemokines, and growth factors upon 2-HOBA treatment and further points to biofunctions related to the recruitment, attraction, and movement of different immune cell types. In conclusion, 2-HOBA significantly altered the protein biomarkers CCL19, IL-12β, IL-20Rα, TNFβ, and TWEAK, and these may be responsible for the protective effects of 2-HOBA against reactive electrophiles, such as IsoLGs, commonly expressed in conditions of excessive oxidative stress. 2-HOBA has a role as a IsoLG scavenger to proactively improve immune health in a variety of conditions.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10753-023-01801-w.

ObjectiveTo determine the effects of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on strength, muscle mass, and contractile material in muscle wasting induced by onabotulinumtoxin type-A (BoNT-A) injection into the quadriceps femoris muscles of New Zealand white rabbits.MethodsA total of 21, female rabbits were divided into 3 groups (n = 7, each). Group 1 (Control) received intramuscular injection of saline. Groups 2 and 3 received intramuscular injection of BoNT-A (3.5 units/kg), with group 3 receiving supplementation with HMB (120 mg/kg-BW/day). Muscle morphology, mass, and strength were assessed 8 weeks later in both injected and non-injected contralateral limbs.ResultsInjected muscle strength of group 2 (BoNT-A) and group 3 (BoNT-A+HMB) was reduced by 63% and 60%, respectively, compared with Controls (p < 0.0001). Strength in contralateral muscles of group 2 was reduced by 23% vs Controls (p <0.002), while in group 3, strength was similar to Controls. Muscle mass in the injected muscles of the BoNT-A and BoNT-A+HMB groups was significantly reduced, by 46% and 48%, respectively.ConclusionWhile HMB did not prevent loss of muscle strength and mass in the BoNT-A-injected musculature, it prevented significant loss of contractile material in the injected musculature and strength loss in the contralateral non-injected musculature.LAY ABSTRACTOnabotulinum toxin A (BoNT-A) is currently approved for cosmetic procedures and for the treatment of many conditions, such as migraine headaches and neuromuscular conditions associated with spasticity, such as cerebral palsy or post-stroke in USA. Once injected into the muscle BoNT-A causes muscle paralysis, which is reversible. The current study examined the local and distant detrimental effects of BoNT-A on decreasing muscle wasting and muscle function in a rabbit model, and the effects of dietary use of HMB (β-hydroxy-βmethylbutyrate), a leucine metabolite, on these detrimental effects. BoNT-A was injected into 1 leg of a rabbit model and muscle mass and strength measured in both the injected and non-injected legs. BoNT-A caused a loss of muscle mass in the injected legs. It also caused a loss of strength in the injected legs and a somewhat reduced loss of strength in the non-injected legs. This suggests that BoNT-A injections can cause a decrease in function in distant, non-target muscles. HMB partially reversed some of the detrimental side-effects of BoNT-A, being shown to be effective in maintaining muscle strength in the non-injected leg.

The extensive collection of glossy (gl) and eceriferum (cer) mutants of maize and Arabidopsis have proven invaluable in dissecting the branched metabolic pathways that support cuticular lipid deposition. This bifurcated pathway integrates a fatty acid elongation‐decarbonylative branch and a fatty acid elongation‐reductive branch, which collectively has the capacity to generate hundreds of cuticular lipid metabolites. In this study, a combined transgenic and biochemical strategy was implemented to explore and compare the physiological function of three homologous genes, Gl2, Gl2‐like, and CER2, in the context of this branched pathway. These biochemical characterizations integrated new extraction chromatographic procedures with high spatial resolution mass spectrometric imaging methods to profile the cuticular lipids on developing floral tissues transgenically expressing these transgenes in wild‐type or cer2 mutant lines of Arabidopsis. Collectively, these datasets establish that both the maize Gl2 and Gl2‐like genes are functional homologs of the Arabidopsis CER2 gene. In addition, the dynamic distribution of cuticular lipid deposition follows distinct floral organ localization patterns indicating that the fatty acid elongation‐decarbonylative branch of the pathway is differentially localized from the fatty acid elongation‐reductive branch of the pathway.

SummaryWhat do you do after plunger lifting? What if lift gas is not readily available or your liquid level is around a bend? What can you do with a well that has low reservoir pressure, liquid-loading trouble, and fragile economics? Do you give up on the remaining reserves and advance to plugging and abandonment? These questions were considered, and the answers were found to be unsatisfactory. This paper will describe the development and testing of a novel wireline-deployed positive-displacement pump (WLPDP) that was invented to address these challenges.Artificial-lift (AL) pumps have historically been developed with high-producing oil wells in mind. Pumps for late-life wells have mostly been repurposed from these applications and optimized for reduced liquids production. The WLPDP development began with the constraints of late-life wells with the goal of addressing reserves that conventional AL methods would struggle to produce profitably. Internal and industry-wide data were first reviewed to determine what WLPDP specifications would address the majority of late-life wells. The primary target was gas wells, although “stripper” oil wells were also considered. The resulting goal was a pump that could deliver 30 BFPD from 10,000-ft true vertical depth (TVD).The pumping system must be cost-effective to be a viable solution, which led to several design boundaries. Pumps fail and replacement costs can drive economics, so the system must be deployable/retrievable through tubing. The majority of new onshore wells have tortuous geometries, so the system must be able to function at the desired depth despite them—without damaging associated downhole components. The system should use as many off-the-shelf components and known technologies as possible to reduce development costs and encourage integration. Finally, the pump should be able to handle a variety of wellbore liquids, produced gases, and limited solids.The WLPDP was designed to meet the established specifications and boundary conditions. The 2.25-in.-outer-diameter (OD) pump is deployed through tubing. and powered with a standard wireline (WL) logging cable. The cable powers a direct-current (DC) motor that drives an axial piston pump. The piston pump circulates a dielectric oil between two bladders by means of a switching valve. When each bladder expands, it pressurizes inlet-wellbore liquids, pushing them out of the well. Produced gas flows in the annulus between the tubing and production casing. The intake/discharge check valves and bladders are the only internal pump components that contact the wellbore fluids.The WLPDP system was able to meet the design-volume/pressure specifications in all orientations, as confirmed through laboratory and integration testing. Targeted studies were conducted to verify/improve check-valve reliability, gas handling, elastomer suitability, and cable-corrosion resistance. The results of these and related studies will be discussed in the paper.

2-hydroxybenzylamine (2-HOBA), a naturally occurring compound found in buckwheat, has potential for use as a nutrition supplement due to its ability to protect against the damaging effects of oxidative stress. In a series of rodent toxicity studies, 2-HOBA acetate was well-tolerated and did not produce any toxic effects over 28 or 90 days of repeated oral administration. However, it remained necessary to test the potential toxicity of 2-HOBA acetate in a non-rodent species. In this investigation, 2-HOBA acetate was orally administered to male and female New Zealand White Rabbits for 90 days at doses of 100, 500, and 1000 mg·kg BW−1·day−1 (n = 5 per sex/group). As previously observed in rodents, 2-HOBA acetate administration was well tolerated. No toxic effects of 2-HOBA acetate were detected in body weight, feed consumption, hematology, blood chemistry, urine chemistry, organ weights, gross pathology or histopathology. Based on these findings, the no-observed-adverse-effect-level of 2-HOBA acetate in rabbits was determined to be 1000 mg·kg BW−1·day−1, which was the highest dose tested. These results provide further support for the safety of 2-HOBA acetate administration.

β-Hydroxy-β-methylbutyrate (HMB) is a leucine metabolite available in calcium salt (CaHMB) and free acid forms as a sports nutrition ergogenic aid. HMB has also been used to support muscle health in the elderly and other populations needing to maintain muscle mass. Several human studies have reported safety data for CaHMB, and rodent sub-chronic toxicity studies have been conducted; however, there are no published genotoxicity studies for HMB. Therefore, three studies (a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian cell micronucleus test) were performed. In the Ames test, no changes in revertant colonies or background were noted with CaHMB concentrations up to 5000 μg per plate, either with or without metabolic activation in five bacterial strains. In the chromosomal aberration test, the number of aberrations associated with up to 2.5 mM CaHMB (long-term) or 10.0 mM (short-term) were similar to those observed for negative controls (<5%), and no polyploidy was observed. Lastly, in the mammalian micronucleus test, no changes in immature erythrocyte or micronuclei frequencies were observed in animals treated with up to 2000 mg·kg−1 body weight CaHMB. In conclusion, CaHMB was determined to have no genotoxic effects.

BACKGROUND: Vitamin D status (VITD) has been related to impaired skeletal muscle function, and may be associated with recovery after muscle injury. Limited data exists on the relationship between VITD concentrations, muscle damage and inflammatory markers from an acute bout of exercise. PURPOSE: Examine the effect of VITD concentrations on acute physiological responses and recovery indices from resistance exercise. METHODS: 15 resistance trained men (24±4 y) with at least 2 years of resistance training experience volunteered to participate in this study. Participants were grouped into a low 25(OH)-VITD (LVD; 26.7±1.7 ng·ml-1; n=7) or high 25(OH)-VITD (HVD; 37.2±7.2 ng·ml-1; n=8) group based upon baseline (BL) 25(OH)-VITD concentrations. Participants performed 8 sets of 10-12 repetitions at 70% of the maximal strength of the squat exercise, with 75 s of rest between sets. Performance [counter movement jump (CMJP), endocrine (testosterone [T] and cortisol [C]), inflammatory (IL-6 and C-reactive protein [CRP]), and muscle damage (creatine kinase [CK] and myoglobin [MB]) assessments were performed at BL, 30-min, 24-h, 48-h and 72-h post-exercise. Data was analyzed using a repeated measures ANOVA. To complement this procedure, magnitude based inferences were used to provide additional interpretation of the differences that VITD concentrations may have had on the recovery response. RESULTS: No significant interactions were noted between LVD and HVD in CMJP (p=0.26), C (p=0.97), T (p=0.21), CRP (p=0.30), IL-6 (p=0.58) or CK (p=0.16) responses to the exercise protocol. However, a significant interaction was observed in MB (p=0.05) responses. Although post-hoc analyses failed to see any significant differences between the groups at any time point, inferential analysis indicated that MB concentrations was “likely” higher at 30-min for LVD (87.2±57.4 ng·ml-1) than HVD (51.3±21.9 ng·ml-1). CRP levels were “likely” lower at 24-h (549±373 mg·L-1 vs.1344±1654 mg·L-1) and 48-h (565±386 mg·L-1 vs.1079±1077 mg·L-1) for HVD. Inferences for all other comparisons were unclear. CONCLUSIONS: Results indicated that HVD provides a degree of resiliency towards acute muscle damage and enhances recovery of high velocity resistance exercise compared to LVD. Further research using greater sample size appears warranted.