Metabolic rescue of α-synuclein-induced neurodegeneration through propionate supplementation and intestine-neuron signaling in C. elegans.

Microbial metabolites that can modulate neurodegeneration are promising therapeutic targets. Here, we found that the short-chain fatty acid propionate protects against α-synuclein-induced neuronal death and locomotion defects in a Caenorhabditis elegans model of Parkinson's disease (PD) through bidirectional regulation between the intestine and neurons. Both depletion of dietary vitamin B12, which induces propionate breakdown, and propionate supplementation suppress neurodegeneration and reverse PD-associated transcriptomic aberrations. Neuronal α-synuclein aggregation induces intestinal mitochondrial unfolded protein response (mitoUPR), which leads to reduced propionate levels that trigger transcriptional reprogramming in the intestine and cause defects in energy production. Weakened intestinal metabolism exacerbates neurodegeneration through interorgan signaling. Genetically enhancing propionate production or overexpressing metabolic regulators downstream of propionate in the intestine rescues neurodegeneration, which then relieves mitoUPR. Importantly, propionate supplementation suppresses neurodegeneration without reducing α-synuclein aggregation, demonstrating metabolic rescue of neuronal proteotoxicity downstream of protein aggregates. Our study highlights the involvement of small metabolites in the gut-brain interaction in neurodegenerative diseases.

The Effect of Osthole on Transient Receptor Potential Channels: A Possible Alternative Therapy for Atopic Dermatitis.

Introduction: Chronic recurrent skin inflammation and severe itching in patients with atopic dermatitis (AD) significantly impair their quality of life. The H4 histamine receptor plays a key role in histamine-induced itching. During the skin inflammation associated with AD, pro-inflammatory mediators (interleukins, cytokines) are released from neurons. Ultimately, a cascade of reactions leads to the activation and sensitization of transient receptor potential channels (TRP), which exacerbate the inflammation and itching associated with AD. Osthole (OST) is a natural coumarin with a proven versatile pharmacological effect: anti-cancer, anti-inflammatory and immunomodulatory. However, the molecular mechanism of OST in relieving inflammation in histamine-mediated itching is not yet clear. Purpose: In the studies presented, the possible effect of the OST action on the inhibition of the gene expression of the histamine H4 receptor and the key genes of the TRP channels as well as on the concentration of proinflammatory interleukins was analyzed. Methods: Inflammation was induced in a 3D skin model and a keratinocyte cell line Normal Human Epidermal Keratinocytes (NHEK) identical to that of AD, and then OST was administered at various doses. The concentrations of IL-4/-13 were determined by ELISA. RNA was isolated from the 3D skin cells and the NHEK cell line, and the qPCR method was used to determine the expression of: IL-4α, H4R, TRPV1, TRPV4, TRPM8 analyzed. Results: The study showed that OST significantly reduced the secretion of IL-4/-13 in a keratinocyte cell line and in a 3D skin model. In addition, OST was found to significantly decrease the gene expression of IL-4α, H4R, TRPV1, TRPV4 and increase TRPM8 in both the NHEK cell line and the organotypic 3D skin model. Conclusion: The data obtained provide the first in vitro evidence of itch relief following the application of OST to atopic skin. Research on the use of OST as an active component of emollients in the treatment of AD should be continued in the future.

Chromium propionate in turkeys: effects on insulin sensitivity.

The objective of this study was to evaluate the effects of dietary chromium (Cr), as Cr propionate (Cr Prop), on measures of insulin sensitivity in turkeys. Plasma glucose and nonesterified fatty acid (NEFA), and liver glycogen concentrations were used as indicators of insulin sensitivity. One-day-old Nicholas Large White female poults (n = 336) were randomly assigned to dietary treatments consisting of 0 (control), 0.2, 0.4, or 0.6 mg supplemental Cr/kg diet. Each treatment consisted of 12 replicate cages with 7 turkeys per cage. Final BW were taken on d 34, and on d 35 two birds from each cage were sampled for plasma glucose and NEFA, and liver glycogen determination at the initiation (fed state) and termination (fasted state) of a 24-h fast. Following a 24-h fast, 2 turkeys per cage were refed (refed state) their treatment diet for 4 h, and then harvested. Feed/gain and ADG did not differ between control and Cr-supplemented turkeys over the 34-d study, but feed intake tended (P = 0.071) to be greater for controls than turkeys receiving 0.4 mg Cr/kg diet. Fed turkeys had greater plasma glucose (P = 0.002) and liver glycogen (P = 0.001) concentrations, and lower (P = 0.001) NEFA concentrations than fasted birds. Turkeys refed after fasting had greater (P = 0.001) plasma glucose and liver glycogen concentrations, and lower (P = 0.001) plasma NEFA levels than fed turkeys. Liver glycogen and plasma NEFA concentrations did not differ among control and Cr-supplemented birds in the fed, fasted, or refed state. Plasma glucose concentrations were not affected by treatment in fed or fasted turkeys. Turkeys supplemented with 0.2 or 0.4 mg Cr/kg and refed after fasting had lower (quadratic, P = 0.038) plasma glucose concentrations than controls. Plasma glucose concentrations in refed birds did not differ among Cr-supplemented turkeys. The lower plasma glucose concentration in Cr-supplemented turkeys following refeeding is consistent with Cr enhancing insulin sensitivity.

Chromium propionate in turkeys: effect on performance and animal safety.

Two hundred eighty-eight male Nicholas Large White turkey poults were used to determine the effect of supplementing turkeys with chromium propionate (Cr Prop) from 1 to 84 d of age on performance and animal safety. Treatments consisted of Cr prop supplemented to provide 0, 0.2, or 1.0 mg Cr/kg diet. One mg of supplemental Cr is 5 times (x) the minimal concentration of Cr Prop that enhanced insulin sensitivity in turkeys. Each treatment consisted of 8 floor pens with 12 poults per pen. Turkeys were individually weighed initially, and at the end of the starter 1 (d 21), starter 2 (d 42), grower 1 (d 63), and grower 2 phase (d 84). On d 85, blood was collected from the wing vein in heparinized tubes from 2 turkeys per pen for plasma chemistry measurements. A separate blood sample was collected from the same turkeys in tubes containing K2EDTA for hematology measurements. Turkey performance was not affected by treatment during the starter 1 phase. Gain was greater (P = 0.024) and feed/gain lower (P = 0.030) for turkeys supplemented with Cr compared with controls during the starter 2 phase. Over the entire 84-d study turkeys supplemented with Cr had greater (P = 0.005) ADG and tended (P = 0.074) to gain more efficiently than controls. Gain (P = 0.180) and feed/gain (P = 0.511) of turkeys supplemented with 0.2 mg Cr/kg did not differ from those receiving 1.0 mg Cr/kg over the entire 84-d study. Feed intake was not affected by treatment. Body weights of turkeys supplemented with Cr were heavier (P = 0.005) than controls by d 84. Chromium supplementation did not affect hematological measurements and had minimal effect on plasma chemistry variables. Results of this study indicates that Cr Prop supplementation can improve turkey performance, and is safe when supplemented to turkey diets at 5x the minimal concentration that enhanced insulin sensitivity.

Chromium propionate supplementation to energy- and protein-reduced diets reduces feed consumption but improves feed conversion ratio of yellow-feathered male broilers in the early period and improves meat quality.

Growth performance and carcass traits may be retarded by low nutrient density diets. Organic chromium propionate (CrProp) can improve growth, carcass traits, and meat quality in farmed lambs, white broilers, and fish. Limited data regarding CrProp's impacts on yellow-feathered broilers are available. Eight hundred yellow-feathered male broilers (1-day old) were randomly allocated to 4 dietary groups and reared for 56 d. The trial was a 2 (dietary nutrient density) ×2 (CrProp) factorial arrangement with 4 diets: regular nutrient diet and low nutrient density (LND, reduction in metabolizable energy by 81 kcal and crude protein by 0.43%) diet supplemented with or without 200 mg/kg CrProp. Broilers were euthanized at d 56 after blood collection. The results indicated that the LND diet led to greater average daily feed intake (ADFI) from d 1 to 42 and feed conversion ratio (FCR) from d 22 to 42 (P < 0.05). Supplementation of CrProp improved body weight (BW) from d 1 to 56, average daily gain (ADG), and FCR during d 1 to 42 but reduced ADFI during d 1 to 21, as well as lowered abdominal fat percentage (P < 0.05). Supplementation with CrProp to regular and LND diets reduced ADFI but improved FCR from d 1 to 21 (P < 0.05). The LND diet lowered total antioxidant capacity (T-AOC) concentration and total superoxide dismutase (T-SOD) activity in the jejunal mucosa. CrProp elevated T-AOC levels and glutathione peroxidase activity (GSH-Px, P < 0.05). Dietary CrProp upregulated (P < 0.05) the expression of fatty acid transporter (FABP1) gene and peptide transporter (Pept1) gene. CrProp administration increased jejunal FABP1 expression and lowered cooking loss of breast meat (P < 0.05) in the LND group while reducing shear force (P = 0.009) of broilers treated by regular diet. In summary, CrProp administration to the LND diet can improve growth performance in the starter period and meat quality on d 56, possibly through upregulated nutrient transporter gene expression in the jejunum and enhanced antioxidant capability.

Influence of Prolonged Whole Egg Supplementation on Insulin-like Growth Factor 1 and Short-Chain Fatty Acids Product: Implications for Human Health and Gut Microbiota.

The gut microbiota exert a profound influence on human health and metabolism, with microbial metabolites playing a pivotal role in shaping host physiology. This study investigated the impact of prolonged egg supplementation on insulin-like growth factor 1 (IGF-1) and circulating short-chain fatty acids (SCFAs). In a subset of a cluster-randomized trial, participants aged 8-14 years were randomly assigned into three groups: (1) Whole Egg (WE)-consuming 10 additional eggs per week [n = 24], (2) Protein Substitute (PS)-consuming yolk-free egg substitute equivalent to 10 eggs per week [n = 25], and (3) Control Group (C) [n = 26]. At week 35, IGF-1 levels in WE significantly increased (66.6 ± 27.7 ng/mL, p < 0.05) compared to C, with positive SCFA correlations, except acetate. Acetate was stable in WE, increasing in PS and C. Significant propionate differences occurred between WE and PS (14.8 ± 5.6 µmol/L, p = 0.010). WE exhibited notable changes in the relative abundance of the Bifidobacterium and Prevotella genera. Strong positive SCFA correlations were observed with MAT-CR-H4-C10 and Libanicoccus, while Roseburia, Terrisporobacter, Clostridia_UCG-014, and Coprococcus showed negative correlations. In conclusion, whole egg supplementation improves growth factors that may be related to bone formation and growth; it may also promote benefits to gut microbiota but may not affect SCFAs.

Efficacy of calcium propionate against fungicide-resistant fungal plant pathogens and suppression of botrytis blight of ornamental flowers.

Conventional fungicides are used in IPM programs to manage fungal plant pathogens, but there are concerns about resistance development in target organisms, environmental contamination, and human health risks. This study explored the potential of calcium propionate (CaP), a common food preservative generally recognized as safe (GRAS) to control fungicide-resistant plant pathogens, mainly Botrytis cinerea, and botrytis blight in ornamentals. In-vitro experiments using mycelium growth inhibition indicated a mean EC50 value for CaP (pH 6.0) of 527 mg/L for six isolates of Botrytis cinerea as well as 618, 1354, and 1310 mg/L for six isolates each of Monilinia fructicola, Alternaria alternata, and Colletotrichum acutatum. In vitro efficacy tests indicated CaP equally inhibited mycelium growth of fungal isolates sensitive and resistant to FRAC codes 1, 2, 3, 7, 9, 11, 12, and 17 fungicides. CaP at 0.1% (pH 6.0-6.5) reduced infection cushion (IC) formation in vitro, botrytis blight on petunia flowers, and botrytis blight of cut flower roses with little to no visible phytotoxicity. Although higher concentrations strongly inhibited infection cushion formation, they did not improve efficacy and exhibited phytotoxicity. We hypothesize that high concentrations may create tissue damage that facilitates direct fungal penetration without the need for infection cushion and subsequent appressoria formation. This study indicates the potential usefulness of CaP for blossom blight disease management in ornamentals if applied at concentrations low enough to avoid phytotoxicity.

Effects of Chromium Propionate and Calcium Propionate on Lactation Performance and Rumen Microbiota in Postpartum Heat-Stressed Holstein Dairy Cows.

Chromium propionate (Cr-Pro) and calcium propionate (Ca-Pro) are widely applied in dairy production, especially in the alleviation of heat stress (HS). HS can reduce the abundance of rumen microbiota and the lactation performance of dairy cows. The present work mainly focused on evaluating the effects of Cr-Pro and Ca-Pro on the performance, ruminal bacterial community, and stress of postpartum HS dairy cows as well as identifying the differences in their mechanisms. Fifteen multiparous postpartum Holstein cows with equivalent weights (694 ± 28 kg) and milk yields (41.2 ± 1.21 kg/day) were randomly divided into three groups: control (CON), Cr-Pro (CRPR), and Ca-Pro (CAPR). The control cows received the basal total mixed ration (TMR) diet, while the CRPR group received TMR with 3.13 g/day of Cr-Pro, and the CAPR group received TMR with 200 g/day of Ca-Pro. The rumen microbial 16S rRNA was sequenced using the Illumina NovaSeq platform along with the measurement of ruminal volatile fatty acids (VFAs) and milking performance. Cr-Pro and Ca-Pro improved lactation performance, increased the rumen VFA concentration, and altered the rumen microbiota of the HS dairy cows. Cr-Pro significantly improved the milk yield (p < 0.01). The richness and diversity of the microbial species significantly increased after feeding on Ca-Pro (p < 0.05). Gene function prediction revealed increased metabolic pathways and biological-synthesis-related function in the groups supplemented with Cr-Pro and Ca-Pro. Our results indicate that the application of Cr-Pro or Ca-Pro can provide relief for heat stress in dairy cows through different mechanisms, and a combination of both is recommended for optimal results in production.

The effects of chromium propionate supplementation to yearling steers in a commercial feedyard on growth performance, carcass characteristics, and health.

British crossbred steers (n = 3,072; initial body weight [BW] = 358 ±â€…37 kg) were used to evaluate the effects of chromium propionate supplementation to yearling steers in a commercial feedyard on growth performance, carcass characteristics, and health. Steers were blocked by initial BW; pens were assigned randomly to one of two dietary treatments within block. Treatments, replicated in 15 pens per treatment with 75 to 135 heads per pen, included 1) control, 0 mg supplemental Cr/kg dietary dry matter (DM) (CTL); 2) 0.50 mg supplemental Cr/kg diet DM (chromium propionate; KemTRACE Chromium 0.4%, Kemin Industries, Des Moines, IA) (chromium propionate, CR). Final BW (638 vs. 641 kg), average daily gain (1.81 vs. 1.82 kg), DM intake (11.02 vs. 11.02 kg), and gain efficiency (0.164 vs. 0.165) did not differ between CTL and CR, respectively (P ≥ 0.75). No differences among treatments for hot carcass weight (407 vs. 408 kg, CTL and CR, respectively), dressing percentage, longissimus muscle area, or yield grade were observed (P ≥ 0.15). Twelfth-rib fat thickness tended (P = 0.10) to be greater for CR vs. CTL (1.55 vs. 1.29 cm, respectively). A trend (P = 0.10) for marbling score to be higher for CR vs. CTL was detected (452 vs. 440, respectively). Distribution of quality grade was similar between CR and CTL; 1.52% of carcasses graded prime (P = 0.68), and 87.2% of carcasses graded choice (P = 0.68). Respiratory morbidity was low (1.93%) and not different among treatments (P = 0.20); likewise, there was no difference in respiratory treatment rates between treatments (P ≥ 0.18). Supplementing Cr to high-performing yearling steers did not alter growth performance, carcass characteristics, or health outcomes.

Review: State of the knowledge on the importance of folates and cobalamin for dairy cow metabolism.

Synthesis of B vitamins by the rumen microbiota is usually sufficient to avoid the appearance of clinical deficiency symptoms in dairy cows under normal feeding conditions. Nevertheless, it is now generally accepted that vitamin deficiency is much more than the appearance of major functional and morphological symptoms. Subclinical deficiency, which is present as soon as the supply is lower than the need, causes cellular metabolic changes leading to a loss of metabolic efficiency. Folates and cobalamin, two B vitamins, share close metabolic relationships. Folates act as co-substrates in one-carbon metabolism, providing one-carbon unit for DNA synthesis and de novo synthesis of methyl groups for the methylation cycle. Cobalamin acts as a coenzyme for reactions in the metabolism of amino acids, odd-numbered chain fatty acids including propionate and de novo synthesis of methyl groups. Both vitamins are involved in reactions to support lipid and protein metabolism, nucleotide synthesis, methylation reactions and possibly, maintenance of redox status. Over the last decades, several studies have reported the beneficial effects of folic acid and vitamin B12 supplements on lactation performance of dairy cows. These observations indicate that, even when cows are fed diets adequately balanced for energy and major nutrients, B-vitamin subclinical deficiency could be present. This condition reduces casein synthesis in the mammary gland and milk and milk component yields. Folic acid and vitamin B12 supplements, especially when given together, may alter energy partitioning in dairy cows during early and mid-lactation as indicated by increased milk, energy-corrected milk, or milk component yields without affecting DM intake and BW or even with reductions in BW or body condition loss. Folate and cobalamin subclinical deficiency interferes with efficiency of gluconeogenesis and fatty acid oxidation and possibly alters responses to oxidative conditions. The present review aims to describe the metabolic pathways affected by folate and cobalamin supply and the consequences of a suboptimal supply on metabolic efficiency. The state of knowledge on the estimation of folate and cobalamin supply is also briefly mentioned.

Isolation and characterization of a new oxyphenisatin analogue, oxyphenisatin propionate, from a processed plum intended as a weight loss product.

A new oxyphenisatin analogue was detected from a processed plum claiming to be a weight loss product without any side effects during the daily inspecting and monitoring of illegal adulterants in health supplements. An abundant peak caused our interest firstly owing to its identical fragments of m/z 224 and 196 in the MS/MS experiments with those of oxyphenisatin acetate. The chemical structure of the unknown compound was characterized by ultra-high performance liquid chromatography equipped with diode array detector and quadrupole time-of-flight tandem mass spectrometry (UHPLC-DAD-Q-TOF/MS), followed by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy experiments. Based on the data, it was defined that the two symmetrical acetyl groups in oxyphenisatin acetate were replaced by two propionyl groups for the unknown structure. Finally, the new oxyphenisatin analogue was identified as 3,3-bis[4'-(propionyloxy)phenyl]-1,3-dihydroindole-2-one and designated as oxyphenisatin propionate. Thereafter, the content of the new analogue was quantitatively determined to be 681 mg/kg, which would inevitably cause adverse health effect because there was not specification for daily consumption of this product. To the best of our knowledge, this is the first report for identification of oxyphenisatin propionate.

Effect of acupuncture at Xinwu acupoint combined with loratadine and fluticasone propionate on symptom alleviation, nasal function, and serum histamine level in patients with allergic rhinitis.

OBJECTIVE: To determine the influence of acupuncture at the Xinwu acupoint combined with western medicine (loratadine and fluticasone propionate) on symptom alleviation, nasal mucociliary clearance velocity (MCV), and serum histamine level of patients with allergic rhinitis (AR). METHODS: A total of 122 patients with AR treated in Gansu province hospital of TCM and The Third People's Hospital of Gansu Province from April 2019 to April 2021 were retrospectively analyzed. Among them, 54 patients treated with loratadine and fluticasone propionate were assigned to the control group, and 68 patients treated with additional acupuncture at the Xinwu acupoint based on treatment of the control group were assigned to the observation group. The treatment efficacy of the two groups was compared, and the scores of main symptoms and nasal function were also compared before and after therapy. Additionally, the two groups were compared in the levels of histamine, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and immunoglobulin E (IgE) before and after therapy. RESULTS: After therapy, the observation group yielded a higher total effective rate than the control group (P=0.006) and had lower symptom scores than the control group (P<0.001). Additionally, the MCV of the two groups increased (P<0.001), and the nasal mucociliary transit time (MTT) and nasal resistance (NR) of both groups decreased (P<0.001) after therapy. The observation group showed a greatly better improvement of nasal function than the control group (P<0.001). Moreover, after therapy, the observation group showed lower histamine and IgE levels than the control group (P<0.01) and the observation group presented significantly lower levels than the control group, and had lower rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores than the control group (P<0.001). The two groups were not different in the incidence of adverse reactions (P=0.886). CONCLUSION: Acupuncture at Xinwu acupoint combined with loratadine and fluticasone propionate can deliver a powerful efficacy on AR and alleviate the clinical symptoms, without increasing adverse reactions.

Effect of propionate, monensin, and saccharomyces cerevisiae or their combination on production and rumen fermentation of holstein steers.

This study aimed to evaluate the effects of calcium propionate (PrCa), PrCa + monensin sodium (PrCa + Mon), and PrCa + Saccharomyces cerevisiae (PrCa + Sc) on the productive performance of Holstein steers. Twenty-four Holstein steers (270.0 ± 25.85 kg) were distributed individually into four treatments of six replicates. The treatments were control (no additives), PrCa (10 g/kg), PrCa + Mon (10 g/kg + 30 mg/kg), and PrCa + Sc (10 g/kg + 12.8 × 109 cfu). The steers were fed for 43 days, and afterwards, nutrient intake and digestibility as well as volatile fatty acids were determined, while the weight gained, feed efficiency, and CH4 production were calculated. Diet of PrCa + Sc had the highest (P < 0.0001) acid detergent fiber intake and propionate acid as well as the nutrient digestibility, with lowest (P < 0.0001) rumen acetic acid, methane, and protozoa concentration versus other diets. In conclusion, dietary inclusion of PrCa + Sc (10 g/kg + 12.8 × 109 cfu) improved nutrient digestibility, rumen fermentation, and reduced methane emission, thereby enhancing the possibility of ecofriendly ruminant farming.

Protective effects of Chromolaena odorata extract on experimental benign prostatic hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is an age-related disease in dogs and man leading to prostate enlargement which impinges on the urethra causing urinary outflow obstruction. Due to the side effects of surgery and chemotherapy used for the treatment of this disease, attention is now focused on phytotherapeutics for its management. Thus, we investigated the inhibitory effect of hydro-methanol extract of Chromolaena odorata (HMECO) on testosterone propionate (TP)-induced BPH rat model. A total of forty-two 10-12 weeks old male Sprague-Dawley outbred albino rats (Rattus norvegicus) weighing 200 - 250 g were randomly divided into six equal groups of seven rats each based on body weight as follows: A) Control group given phosphate-buffered saline orally and corn oil subcutaneously (SC) once daily, B) TP at a dose of 3.00 mg kg-1 SC once daily, C) TP at a dose of 3.00 mg kg-1 SC and finasteride at a dose of 10.00 mg kg-1 orally once daily, D) TP at a dose of 3.00 mg kg-1 SC plus 200 mg kg-1 HMECO orally once daily, E) TP at a dose of 3.00 mg kg-1 SC plus 400 mg kg-1 HMECO orally once daily and F) TP at a dose of 3.00 mg kg-1 SC plus 800 mg kg-1 HMECO orally once daily for 28 days. Results showed that HMECO significantly reduced prostate weight, prostatic index; serum levels of testosterone and prostatic epithelial thickness and increased luminal diameter in BPH induced rats. Thus, the results of this study suggest that C. odorata is a potential pharmacological candidate for the management of BPH.

Sodium Propionate or Sodium Butyrate Promotes Fatty Acid Oxidation in HepG2 Cells Under Oxidative Stress.

The beneficial effects of sodium butyrate (NaB) and sodium propionate (NaP) on fatty acid oxidation (FAO) genes and production of proinflammatory cytokines related to nonalcoholic fatty liver disease (NAFLD) were evaluated using HepG2 human liver hepatocellular carcinoma cells exposed to palmitate/oleate or lipopolysaccharides (LPSs) as a model. The results showed that NaP or NaB was able to promote FAO, regulate lipolysis, and reduce reactive oxygen species production by significantly increasing the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1 alpha (CPT1α), fibroblast growth factor 21 (FGF21), and uncoupling protein 2 (UCP2) in HepG2 cells. Together, NaP and NaB may produce greater effects by increasing CPT1α, PPARα, and UCP2 mRNA expression in LPS-treated HepG2 cells and by increasing CPT1α and ATGL mRNA expression in palmitate-/oleate-treated HepG2 cells. Only NaP treatment significantly increased FGF21 mRNA expression in palmitate-/oleate-treated HepG2 cells. The enzyme-linked immunosorbent assay results revealed that only pretreatment with LPSs and not palmitate/oleate significantly increased tumor necrosis factor alpha (TNF-α) expression in HepG2 cells. NaP alone or in combination with NaB significantly decreased TNF-α expression in LPS-induced HepG2 cells. The expression of interleukin-8 in both models showed no significant differences in all treatments. NaP and NaB show potential for in vivo studies on NAFLD.

Effects of combined addition of 3-nitrooxypropanol and vitamin B12 on methane and propionate production in dairy cows by in vitro-simulated fermentation.

The compound 3-nitrooxypropanol (3-NOP) is a promising methane inhibitor, which performs well in inhibiting methane emission and does not affect animal feed intake and digestibility. However, it causes a significant increase in hydrogen production while suppressing methane emission, resulting in a waste of feed energy. Vitamin B12 is a key factor in the propionate production pathway and thus plays an important role in regulating the hydrogen utilization pathway. In this study, the effects of 3-NOP combined with vitamin B12 supplementation on rumen fermentation and microbial compositional structure in dairy cattle were investigated by simulating rumen fermentation in vitro. Experiments were performed using a 2 × 2-factorial design: two 3-NOP levels (0 or 2 mg/g dry matter) and 2 vitamin B12 levels (0 or 2 mg/g dry matter). Three experiments were performed, each consisting of 4 treatments, 4 replicates, and 4 blanks containing only inoculum. The combined supplementation of 3-NOP and vitamin B12 reduced methane emission by 12% without affecting dry matter digestibility. The combined addition of 3-NOP and vitamin B12 significantly increased the concentration of propionate and reduced the concentration of acetate and the acetate to propionate ratio. At the bacterial level, 3-NOP increased the relative abundances of Christensenellaceae_R-7_group and Lachnospiraceae_NK3A20_group. Vitamin B12 increased the relative abundances of unclassified_f__Prevotellaceae and Prevotellaceae_UCG-003 and decreased the relative abundance of Lachnospiraceae_NK3A20_group. At the archaeal level, the combination of 3-NOP and vitamin B12 increased the relative abundances of Methanobrevibacter_ sp._ Abm4, OTU1125, and OTU95 and decreased the relative abundances of uncultured_methanogenic_archaeon_g__Methanobrevibacter, OTU1147, OTU1056, and OTU55. The results indicated that 3-NOP combined with vitamin B12 could alleviate rumen hydrogen emission and enhance the inhibition of methane emission compared with 3-NOP alone.

Limosilactobacillus reuteri and caffeoylquinic acid synergistically promote adipose browning and ameliorate obesity-associated disorders.

OBJECTIVE: High intake of caffeoylquinic acid (CQA)-rich dietary supplements, such as green coffee bean extracts, offers health-promoting effects on maintaining metabolic homeostasis. Similar to many active herbal ingredients with high pharmacological activities but low bioavailability, CQA has been reported as a promising thermogenic agent with anti-obesity properties, which contrasts with its poor oral absorption. Intestinal tract is the first site of CQA exposure and gut microbes might react quickly to CQA. Thus, it is of interest to explore the role of gut microbiome and microbial metabolites in the beneficial effects of CQA on obesity-related disorders. RESULTS: Oral CQA supplementation effectively enhanced energy expenditure by activating browning of adipose and thus ameliorated obesity-related metabolic dysfunctions in high fat diet-induced obese (DIO) mice. Here, 16S rRNA gene amplicon sequencing revealed that CQA treatment remodeled the gut microbiota to promote its anti-obesity actions, as confirmed by antibiotic treatment and fecal microbiota transplantation. CQA enriched the gut commensal species Limosilactobacillus reuteri (L. reuteri) and stimulated the production of short-chain fatty acids, especially propionate. Mono-colonization of L. reuteri or low-dose CQA treatment did not reduce adiposity in DIO mice, while their combination elicited an enhanced thermogenic response, indicating the synergistic effects of CQA and L. reuteri on obesity. Exogenous propionate supplementation mimicked the anti-obesity effects of CQA alone or when combined with L. reuteri, which was ablated by the monocarboxylate transporter (MCT) inhibitor 7ACC1 or MCT1 disruption in inguinal white adipose tissues to block propionate transport. CONCLUSIONS: Our data demonstrate a functional axis among L. reuteri, propionate, and beige fat tissue in the anti-obesity action of CQA through the regulation of thermogenesis. These findings provide mechanistic insights into the therapeutic use of herbal ingredients with poor bioavailability via their interaction with the gut microbiota. Video Abstract.

Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling.

BACKGROUND: Vascular calcification is a major cause of the high morbidity and mortality of cardiovascular diseases and is closely associated with the intestinal microbiota. Short-chain fatty acids (SCFAs) are derived from the intestinal microbiota and can also regulate intestinal microbiota homeostasis. However, it remains unclear whether exogenous supplementation with propionate, a SCFA, can ameliorate vascular calcification by regulating the intestinal microbiota. This study was conducted to explore the roles of propionate and the intestinal microbiota in the process of vascular calcification. METHODS: In total, 92 patients were enrolled consecutively as the observational cohort to analyse the relationship between SCFAs and vascular calcification in both blood and faecal samples. A rat model of vascular calcification was induced by vitamin D3 and nicotine (VDN) to validate the effect of propionate. Differences in the intestinal microbiota were analysed by 16S ribosomal RNA gene sequencing. Faecal microbiota transplantation and Akkermansia muciniphila transplantation experiments were performed to evaluate the functions of the intestinal microbiota. RESULTS: The results of the observational cohort study revealed that the levels of SCFAs (particularly propionate) in both blood and faecal samples independently correlated negatively with calcification scores (P < 0.01). To verify the activities of propionate, it was provided to VDN-treated rats, and oral or rectal propionate delivery reshaped the intestinal microbiota, resulted in elevated SCFA production, improved intestinal barrier function and alleviated inflammation, ultimately ameliorating vascular calcification. Furthermore, we demonstrated that transplantation of the propionate-modulated intestinal microbiota induced beneficial outcomes similar to those with oral or rectal propionate administration. Interestingly, linear discriminant analysis (LDA) effect size (LEfSe) revealed that oral or rectal propionate administration and propionate-modulated intestinal microbiota transplantation both enriched primarily Akkermansia. Subsequently, we demonstrated that Akkermansia supplementation could ameliorate VDN-induced vascular calcification in rats. CONCLUSIONS: Propionate can significantly ameliorate vascular calcification in VDN-treated rats, and this effect is mediated by intestinal microbiota remodelling. The findings in our study indicate that the intestinal tract-vessel axis is a promising target for alleviating vascular calcification. Video Abstract.

Perinatal Propionate Supplementation Protects Adult Male Offspring from Maternal Chronic Kidney Disease-Induced Hypertension.

Emerging evidence supports that early-life disturbance of gut microbiota has an impact on adult disease in later life. Offspring hypertension can be programmed by maternal chronic kidney disease (CKD). Conversely, perinatal use of gut microbiota-targeted therapy has been implemented to reverse programming processes and prevent hypertension. Short-chain fatty acids (SCFAs), the major gut microbiota-derived metabolites, can be applied as postbiotics. Propionate, one of predominant SCFAs, has been shown to have antihypertensive property. We examined whether perinatal propionate supplementation can prevent offspring hypertension induced by maternal CKD. CKD was induced by chow supplemented with 0.5% adenine for 3 weeks before pregnancy. Propionate (P) was supplemented at 200 mmol/L in drinking water during pregnancy and lactation. Male offspring were divided into four groups (n = 7-8/group): control, CKD, control+propionate (CP), and CKD+propionate (CKDP). Maternal CKD-induced offspring hypertension was reversed by perinatal propionate supplementation. The protective effects of perinatal propionate treatment were related to increased propionate-generating bacteria Clostridium spp. and plasma propionate level, increased expression of renal G protein-coupled receptor 41 (GPR41, a SCFA receptor), augmentation of α-diversity, and shifts in gut microbiota composition. In summary, our results highlight that maternal CKD-induced offspring hypertension can be prevented by the use of gut microbial metabolite SCFAs in early life, which could shed light on the prevention of the current hypertension pandemic.

Dietary supplementation with calcium propionate could beneficially alter rectal microbial composition of early lactation dairy cows.

Dietary supplementation with calcium propionate can effectively alleviate negative energy balance and hypocalcemia of dairy cows in early lactation. The objective of this study was to investigate the effects of calcium propionate feeding levels on the immune function, liver function, and fecal microbial composition of dairy cows in early lactation. Thirty-two multiparous Holstein cows were randomly assigned to four treatments after calving. Treatments were a basal diet plus 0, 200, 350, and 500 g calcium propionate per cow per day throughout a 5-week trial period. Cows were milked three times a day, and blood was sampled to measure immune function and liver function on d 7, 21, and 35. The rectal contents were sampled and collected on d 35 to analyze the microbial composition using 16S rRNA gene sequencing. The results indicated that increasing amounts of calcium propionate did not affected the serum concentrations of total protein, IgG, IgM, and calcium, but the concentrations of albumin and IgA changed quadratically. With the increase of calcium propionate, the activity of serum alanine transaminase and aspartate aminotransferase increased linearly, in contrast, the activity of alkaline phosphatase decreased linearly. Moreover, dietary supplementation with increasing levels of calcium propionate tended to quadratically decrease the relative abundance of Firmicutes while quadratically increased the abundance of Bacteroidetes, and consequently linearly decreased the Firmicutes/Bacteroidetes ratio in the rectal microbiota. Additionally, the supplementation of calcium propionate increased the relative abundances of Ruminococcaceae_UCG-005 and Prevotellaceae_UCG-004 linearly, and Ruminococcaceae_UCG-014 quadratically, but decreased the relative abundances of Lachnospiraceae_NK3A20_group and Family_XIII_AD3011_group quadratically. Compared with the CON group, the calcium propionate supplementation significantly decreased the relative abundance of Acetitomaculum but increased the abundances of Rikenellaceae_RC9_gut_group and Alistipes. In summary, these results suggested that the supplementation of calcium propionate to dairy cows in early lactation could beneficially alter the rectal microbiota.