Transorgan short-chain fatty acid fluxes in the fasted and postprandial state in the pig

Kirschner, Sarah; Have, Gabriella A.M. Ten; Engelen, M.P.; Deutz, N.E.P.

doi:10.1152/ajpendo.00121.2021

Cited by 9 publications

(8 citation statements)

References 42 publications

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“…Likewise, meconium contains relevant concentrations of SCFA (especially acetate and propionate), which supports that microbial action in a piglet's gut commences before Nutrients 2022, 14, 2524 2 of 15 birth [3,5,6]. Short-chain fatty acids (SCFA) may also reach the fetuses via the placenta, as small concentrations are present in maternal blood [7,8]. Postnatally, SCFA, such as acetate, propionate, butyrate, isobutyrate, valerate, isovalerate and caproate, are recognized as important energetic and signaling agents.…”

Section: Introductionmentioning

confidence: 70%

Short-Chain Fatty Acids Modulate Permeability, Motility and Gene Expression in the Porcine Fetal Jejunum Ex Vivo

et al. 2022

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Postnatally, short-chain fatty acids (SCFA) are important energetic and signaling agents, being involved in host nutrition, gut imprinting and immune and barrier function. Whether SCFA exert similar effects during the late fetal phase has been insufficiently elucidated. This study aimed to evaluate whether the fetal jejunum senses SCFA and whether SCFA modify the muscle tension and epithelial permeability and related signaling in jejunal tissue from the porcine fetus in late gestation. Exposure of fetal jejunal tissue to a mix of SCFA (70 µmol/mL) in an organ bath for 20 min lowered the muscle tension. Moreover, SCFA decreased the transepithelial conductance while increasing the short-circuit current in the Ussing chamber, indicating reduced permeability and increased SCFA absorption. Gene expression in the tissues harvested from the Ussing chamber after 30 min indicated downregulation of the expression of receptors (i.e., FFAR2 and TLR2), MCT1 and tight-junction and adherens proteins, which may be a negative feedback response to the applied high SCFA concentration compared with the micromolar concentration detected in fetal gastric fluid. Taken together, our data demonstrate that the fetal jejunum senses SCFA, which trigger electrophysiological, muscle contraction and related gene transcription responses. Hence, SCFA may play a role in prenatal gut nutrition and imprinting.

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Section: Introductionmentioning

confidence: 70%

Short-Chain Fatty Acids Modulate Permeability, Motility and Gene Expression in the Porcine Fetal Jejunum Ex Vivo

et al. 2022

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“…As the SCFAs reaching the systemic circulation are metabolized by peripheral organs, lower muscle mass may reduce the uptake of these energy source, resulting in higher urine levels of isobutyric acid and valerate. 36 Glycine, serine, and threonine are metabolic pathways related to amino acids, and N,N-dimethylglycine, sarcosine, and phosphocholine were frequent metabolites in the PLS-DA models. Slight increase in plasma and muscle amino acid concentration stimulates muscle protein synthesis and secretion of anabolic hormones.…”

Section: Discussionmentioning

confidence: 92%

“…Our study was also the first to show a correlation of oxoisovalerate with muscle mass, which probably occurs through the relationship of SCFAs with systemic inflammation that can be involved in muscle degradation in RA. As the SCFAs reaching the systemic circulation are metabolized by peripheral organs, lower muscle mass may reduce the uptake of these energy source, resulting in higher urine levels of isobutyric acid and valerate 36 …”

Section: Discussionmentioning

confidence: 99%

Urinary metabolomic biomarker candidates for skeletal muscle wasting in patients with rheumatoid arthritis

Oliveira

Santo

Silva

et al. 2023

J cachexia sarcopenia muscle

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Background Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints, leading to chronic synovial inflammation and local tissue destruction. Extra‐articular manifestations may also occur, such as changes in body composition. Skeletal muscle wasting is often observed in patients with RA, but methods for assessing loss of muscle mass are expensive and not widely available. Metabolomic analysis has shown great potential for identifying changes in the metabolite profile of patients with autoimmune diseases. In this setting, urine metabolomic profiling in patients with RA may be a useful tool to identify skeletal muscle wasting. Methods Patients aged 40–70 years with RA have been recruited according to the 2010 ACR/EULAR classification criteria. Further, the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) determined the disease activity. The muscle mass was measured by Dual X‐ray absorptiometry (DXA) to generate the appendicular lean mass index (ALMI) by summing the lean mass measurements for both arms and legs and dividing them by height squared (kg/height2). Finally, urine metabolomic analysis by 1H nuclear magnetic resonance (1H‐NMR) spectroscopy was performed and the metabolomics data set analysed using the BAYESIL and MetaboAnalyst software packages. Principal component analysis (PCA) and partial least squares‐discriminant analysis (PLS‐DA) were applied to the 1H‐NMR data, followed by Spearman's correlation analysis. The combined receiver operating characteristic curve (ROC) was calculated, as well as the logistic regression analyses to establish a diagnostic model. The significance level at P < 0.05 was set for all analyses. Results The total set of subjects investigated included 90 patients with RA. Most patients were women (86.7%), with a mean age of 56.5 ± 7.3 years old and a median DAS28‐CRP of 3.0 (IQR 1.0–3.0). Fifteen metabolites were identified in the urine samples with high variable importance in projection (VIP scores) by MetaboAnalyst. Of these, dimethylglycine (r = 0.205; P = 0.053), oxoisovalerate (r = −0.203; P = 0.055), and isobutyric acid (r = −0.249; P = 0.018) were significantly correlated with ALMI. Based on the low muscle mass (ALMI ≤6.0 kg/m2 for women and ≤8.1 kg/m2 for men) a diagnostic model have been established with dimethylglycine (area under the curve [AUC] = 0.65), oxoisovalerate (AUC = 0.49), and isobutyric acid (AUC = 0.83) with significant sensitivity and specificity. Conclusions Isobutyric acid, oxoisovalerate, and dimethylglycine from urine samples were associated with low skeletal muscle mass in patients with RA. These findings suggest that this group of metabolites may be further tested as biomarkers for identification of skeletal muscle wasting.

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“…In contrast, a relationship between appetite and acetate during exercise has not been identified previously. The intestine is the primary site of acetate production in the fasting and postprandial state (Kirschner et al., 2021), with skeletal muscle becoming a major contributor to acetate production during exercise (Van Hall et al., 2002). Despite limited human evidence, exogenous administration of acetate has been shown to suppress appetite in rodent models, acting via a central homeostatic mechanism (Frost et al., 2014).…”

Section: Discussionmentioning

confidence: 99%

The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study

Frampton

Serrano-Contreras

García-Pérez

et al. 2023

The Journal of Physiology

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An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight‐loss treatment. Metabolic responses to acute exercise are, however, dependent on pre‐exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise‐induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon‐like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, −48.8 pmol/L; exercise: −22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise‐induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. imageKey points Carbohydrate and exercise independently influence key appetite‐regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon‐like peptide 1 and succinate levels.

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Transorgan short-chain fatty acid fluxes in the fasted and postprandial state in the pig

Cited by 9 publications

References 42 publications

Short-Chain Fatty Acids Modulate Permeability, Motility and Gene Expression in the Porcine Fetal Jejunum Ex Vivo

Short-Chain Fatty Acids Modulate Permeability, Motility and Gene Expression in the Porcine Fetal Jejunum Ex Vivo

Urinary metabolomic biomarker candidates for skeletal muscle wasting in patients with rheumatoid arthritis

The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study

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