bims-kimdis 2024-01-07 papers

bims-kimdis

Biomed News

on Ketones, inflammation and mitochondria in disease

Issue of 2024–01–07
seventeen papers selected by
Matías Javier Monsalves Álvarez, Universidad Andrés Bello

[Ketone Body Metabolism and Renal Diseases].
Ketone bodies promote epididymal white adipose expansion to alleviate liver steatosis in response to a ketogenic diet.
A very-low carbohydrate content in a high-fat diet modifies the plasma metabolome and impacts systemic inflammation and experimental atherosclerosis.
Modulation of beta-hydroxybutyrate in traumatic brain injury.
Feasibility and metabolic outcomes of a well-formulated ketogenic diet as an adjuvant therapeutic intervention for women with stage IV metastatic breast cancer: The Keto-CARE trial.
Nutritional adjuncts in the management of gliomas: Food for thought.
Effectiveness of breath acetone monitoring in reducing body fat and improving body composition: A randomized controlled study.
3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights into MFN-2 Mediated Changes.
Rates of diabetic ketoacidosis with empagliflozin use during hospitalization for acute heart failure.
Cannabinoids improve mitochondrial function in skeletal muscle of exhaustive exercise training rats by inhibiting mitophagy through the Pink1/Parkin and Bnip3 pathways.
Effect of intermittent fasting on lipid biokinetics in obese and overweight patients with type 2 diabetes mellitus: prospective observational study.
Low Energy Availability Followed by Optimal Energy Availability Does Not Benefit Performance in Trained Females.
Potential Impact of Bioactive Compounds as NLRP3 Inflammasome Inhibitors: An Update.
Diagnostic agreement between three point-of-care glucose and β-hydroxybutyrate meters and reference laboratory methods in stingrays.
Mitochondrial-derived vesicles in metabolism, disease, and aging.
Macrophage fatty acid oxidation in atherosclerosis.
Mitochondria as secretory organelles and therapeutic cargos.

Sichuan Da Xue Xue Bao Yi Xue Ban. 2023 Nov 20. 54(6): 1091-1096

[Ketone Body Metabolism and Renal Diseases].

Ying Liu, Liang Ma, Ping Fu.

  A ketogenic diet limits energy supply from glucose and stimulates lipolysis, lipid oxidation, and ketogenesis, resulting in elevated levels of ketone bodies in the bloodstream. Ketone bodies are synthesized in the mitochondrial matrix of liver cells and β-hydroxybutyric acid (BHB) is the most abundant type of ketone body. Herein, we reviewed published findings on the metabolism of ketone bodies and the role of BHB in renal diseases. Through blood circulation, ketone bodies reach metabolically active tissues and provides an alternative source of energy. BHB, being a signaling molecule, mediates various types of cellular signal transduction and participates in the development and progression of many diseases. BHB also has protective and therapeutic effects on a variety of renal diseases. BHB improves the prognosis of renal diseases, such as diabetic kidney disease, chronic kidney disease, acute kidney injury, and polycystic kidney disease, through its antioxidant, anti-inflammatory, and stress response mechanisms. Previous studies have focused on the role of ketone bodies in regulating inflammation and oxidative stress in immune cells. Investigations into the effect of elevated levels of ketone bodies on the metabolism of renal podocytes and tubular cells remain inconclusive. Further research is needed to investigate the effect of BHB on podocyte damage and podocyte senescence in renal diseases.

Keywords:  Anti-inflammatory; Anti-oxidative; Ketone body; Renal disease; Review

DOI:  https://doi.org/10.12182/20231160202
J Biol Chem. 2024 Jan 02. pii: S0021-9258(23)02646-7. [Epub ahead of print] 105617

Ketone bodies promote epididymal white adipose expansion to alleviate liver steatosis in response to a ketogenic diet.

Meng-Fei Zhao, Xin-Ge Zhang, Yi-Ping Tang, Ying-Xi Zhu, Hong-Yu Nie, Dan-Dan Bu, Lei Fang, Chao-Jun Li.

  Liver can sense the nutrient status and send signals to other organs to regulate overall metabolic homoeostasis. Herein, we demonstrate that ketone bodies act as signals released from the liver that specifically determine the distribution of excess lipid in epididymal white adipose tissue (eWAT) when exposed to a ketogenic diet (KD). An acute KD can immediately result in excess lipid deposition in the liver. Subsequently, the liver sends the ketone body β-hydroxybutyrate (BHB) to regulate white adipose expansion, including adipogenesis and lipogenesis, to alleviate hepatic lipid accumulation. When ketone bodies are depleted by deleting 3-Hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) gene in liver, the enhanced lipid deposition in eWAT but not in inguinal white adipose tissue (iWAT) is preferentially blocked, while lipid accumulation in liver is not alleviated. Mechanistically, ketone body BHB can significantly decrease lysine acetylation of peroxisome proliferator-activated receptor gamma (PPARγ) in eWAT, causing enhanced activity of PPARγ, the key adipogenic transcription factor. These observations suggest that the liver senses metabolic stress first and sends a corresponding signal, that is, ketone body BHB, to specifically promote eWAT expansion to adapt to metabolic challenges.

Keywords:  adipose remodelling; liver steatosis; liver–adipose signaling axis; peroxisome proliferator-activated receptor gamma; protein acetylation

DOI:  https://doi.org/10.1016/j.jbc.2023.105617
J Nutr Biochem. 2024 Jan 02. pii: S0955-2863(23)00295-4. [Epub ahead of print] 109562

A very-low carbohydrate content in a high-fat diet modifies the plasma metabolome and impacts systemic inflammation and experimental atherosclerosis.

R Castro, K Kalecký, N K Huang, K Petersen, V Singh, A C Ross, T Neuberger, T Bottiglieri.

   BACKGROUND AND AIMS: Ketogenic diets (KD) are very high-fat low-carbohydrate diets that promote nutritional ketosis and are widely used for weight loss, although concerns about potential adverse cardiovascular effects remain. We investigated a very high-fat KD's vascular impact and plasma metabolic signature compared to a non-ketogenic high-fat diet (HFD).
MATERIAL AND METHODS: Apolipoprotein E deficient (ApoE -/-) mice were fed a KD (%kcal: 81:1:18, fat/carbohydrates/protein) or a non-ketogenic high-fat diet with half of the fat content (HFD) (%kcal: 40:42:18, fat/carbohydrates/protein) for 12 weeks. Plasma samples were used to quantify the major ketone body beta-hydroxybutyrate (BHB) and several pro-inflammatory cytokines (IL-6, MCP-1, MIP-1alpha, and TNF alpha), and to targeted metabolomic profiling by mass spectrometry. In addition, aortic atherosclerotic lesions were quantified ex-vivo by magnetic resonance imaging (MRI) on a 14-tesla system.
RESULTS: KD was atherogenic when compared to the control diet, but KD mice when compared to the HFD group (1) had markedly higher levels of BHB and lower levels of cytokines than HFD mice, confirming the presence of ketosis that alleviated the well-established fat-induced systemic inflammation; (2) displayed significant changes in the plasma metabolome that included a decrease in lipophilic and increase in hydrophilic metabolites; (3) had significantly lower levels of several atherogenic lipid metabolites, including phosphatidylcholines, cholesterol esters, sphingomyelins, and ceramides; (4) presented significantly lower aortic plaque burden.
CONCLUSION: KD was atherogenic and was associated with specific metabolic changes but alleviated the fat-induced inflammation and lessened the progression of atherosclerosis when compared to the HFD.

Keywords:  aortic atheroma; apolipoprotein E deficient mice; diets and vascular disease; ketogenic diets; nutritional ketosis

DOI:  https://doi.org/10.1016/j.jnutbio.2023.109562
Curr Opin Clin Nutr Metab Care. 2024 Jan 04.

Modulation of beta-hydroxybutyrate in traumatic brain injury.

Niraj Arora, Dhaval Hitendrakumar Shastri, Utsav Prakashbhai Patel, Kunal Bhatia.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) is a significant public health concern with substantial morbidity and mortality rates in the United States. Current management strategies primarily focus on symptomatic approaches and prevention of secondary complications. However, recent research highlights the potential role of ketone bodies, particularly beta-hydroxybutyrate (BHB), in modulating cellular processes involved in TBI. This article reviews the metabolism of BHB, its effect in TBI, and its potential therapeutic impact in TBI.
RECENT FINDINGS: BHB can be produced endogenously through fasting or administered exogenously through ketogenic diets, and oral or intravenous supplements. Studies suggest that BHB may offer several benefits in TBI, including reducing oxidative stress, inflammation, controlling excitotoxicity, promoting mitochondrial respiration, and supporting brain regeneration. Various strategies to modulate BHB levels are discussed, with exogenous ketone preparations emerging as a rapid and effective option.
SUMMARY: BHB offers potential therapeutic advantages in the comprehensive approach to improve outcomes for TBI patients. However, careful consideration of safety and efficacy is essential when incorporating it into TBI treatment protocols. The timing, dosage, and long-term effects of ketone use in TBI patients require further investigation to fully understand its potential benefits and limitations.

DOI: https://doi.org/10.1097/MCO.0000000000001008
PLoS One. 2024 ;19(1): e0296523

Feasibility and metabolic outcomes of a well-formulated ketogenic diet as an adjuvant therapeutic intervention for women with stage IV metastatic breast cancer: The Keto-CARE trial.

Alex Buga, David G Harper, Teryn N Sapper, Parker N Hyde, Brandon Fell, Ryan Dickerson, Justen T Stoner, Madison L Kackley, Christopher D Crabtree, Drew D Decker, Bradley T Robinson, Gerald Krystal, Katherine Binzel, Maryam B Lustberg, Jeff S Volek.

PURPOSE: Ketogenic diets may positively influence cancer through pleiotropic mechanisms, but only a few small and short-term studies have addressed feasibility and efficacy in cancer patients. The primary goals of this study were to evaluate the feasibility and the sustained metabolic effects of a personalized well-formulated ketogenic diet (WFKD) designed to achieve consistent blood beta-hydroxybutyrate (βHB) >0.5 mM in women diagnosed with stage IV metastatic breast cancer (MBC) undergoing chemotherapy.
METHODS: Women (n = 20) were enrolled in a six month, two-phase, single-arm WFKD intervention (NCT03535701). Phase I was a highly-supervised, ad libitum, personalized WFKD, where women were provided with ketogenic-appropriate food daily for three months. Phase II transitioned women to a self-administered WFKD with ongoing coaching for an additional three months. Fasting capillary βHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three and six months.
RESULTS: Capillary βHB indicated women achieved nutritional ketosis (Phase I mean: 0.8 mM (n = 15); Phase II mean: 0.7 mM (n = 9)). Body weight decreased 10% after three months, primarily from body fat. Fasting plasma glucose, plasma insulin, and insulin resistance also decreased significantly after three months (p < 0.01), an effect that persisted at six months.
CONCLUSIONS: Women diagnosed with MBC undergoing chemotherapy can safely achieve and maintain nutritional ketosis, while improving body composition and insulin resistance, out to six months.

DOI: https://doi.org/10.1371/journal.pone.0296523
Clin Neurol Neurosurg. 2023 Dec 23. pii: S0303-8467(23)00518-8. [Epub ahead of print]236 108102

Nutritional adjuncts in the management of gliomas: Food for thought.

Ashwin Kumaria, Ahmad Kamaludin, Keyoumars Ashkan.



Keywords:  Brain gut axis; Brain tumours; Glioma; Ketogenic diet; Nutrition

DOI:  https://doi.org/10.1016/j.clineuro.2023.108102
J Breath Res. 2024 Jan 04.

Effectiveness of breath acetone monitoring in reducing body fat and improving body composition: A randomized controlled study.

Seonggyu Choi, Minsuk Oh, Oyama Okimitsu, Dong-Hyuk Park, Sunghyun Hong, Tae Ho Lee, Junho Hwang, Hyun-Sook Lee, Yong-Sahm Choe, Wooyoung Lee, Justin Jeon.

  When attempts to lose body fat mass frequently fail, breath acetone monitoring may assist fat mass loss during a low-carbohydrate diet as it can provide real-time body fat oxidation levels. This randomized controlled study aimed to evaluate the effectiveness of monitoring breath acetone levels and providing feedback on fat oxidation during a three-week low-carbohydrate diet intervention. Forty-seven participants (mean age=27.8±4.4 years, 53.3% females, body mass index=24.1±3.4 kg/m2) were randomly assigned to three groups (1:1:1 ratio): daily breath acetone assessment with a low-carbohydrate diet, body weight assessment (body scale) with a low-carbohydrate diet, and low-carbohydrate diet only. Primary outcome was the change in fat mass and secondary outcomes were the changes in body weight and body composition. Forty-five participants completed the study (compliance rate: 95.7%). Fat mass was significantly reduced in all three groups (all P<0.05); however, the greatest reduction in fat mass was observed in the breath acetone group compared to the body scale (differences in changes in fat mass, -1.1 kg; 95% confidence interval: -2.3, -0.2; P=0.040) and control (differences in changes in fat mass, -1.3 kg; 95% confidence interval: -2.1, -0.4; P=0.013) groups. The breath acetone group showed significantly greater reductions in body weight and visceral fat mass than the body scale and control groups (all P<0.05). In addition, the percent body fat and skeletal muscle mass were significantly reduced in both breath acetone and body scale groups (all P<0.05). However, no significant differences were found in changes in body fat percentage and skeletal muscle mass between the study groups. Monitoring breath acetone levels, which could have motivated participants to adhere more closely to the low-carbohydrate diet, to assess body fat oxidation rates may be an effective intervention for reducing body fat mass (compared to body weight assessment or control conditions). This approach could be beneficial for individuals seeking to manage body fat and prevent obesity.

Keywords:  body composition; breath acetone; obesity

DOI:  https://doi.org/10.1088/1752-7163/ad1b19
bioRxiv. 2023 Dec 14. pii: 2023.11.13.566502. [Epub ahead of print]

3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights into MFN-2 Mediated Changes.

Estevão Scudese, Zer Vue, Prassana Katti, Andrea Marshall, Larry Vang, Edgar Garza López, Kit Neikirk, Dominique Stephens, Duane D Hall, Rahmati Rostami, Jian-Qiang Shao, Margaret Mungai, Salma T AshShareef, Innes Hicsasmaz, Sasha Manus, Celestine Wanjalla, Aaron Whiteside, Clintoria Williams, Steven M Damo, Jennifer A Gaddy, Annet Kirabo, Brian Glancy, Estélio Henrique Martin Dantas, André Kinder, Fabiana Scartoni, Matheus Baffi, Melanie R McReynolds, Mark A Phillips, Anthonya Cooper, Sandra A Murray, Vernat Exil, Bret C Mobley, Antentor Hinton.

Sarcopenia is an age-related loss of skeletal muscle, characterized by loss of mass, strength, endurance, and oxidative capacity during aging. Notably, bioenergetics and protein turnover studies have shown that mitochondria mediate this decline in function. Although mitochondrial aging is associated with decreased mitochondrial capacity, the three-dimensional (3D) mitochondrial structure associated with morphological changes in skeletal muscle during aging still requires further elucidation. Although exercise has been the only therapy to mitigate sarcopenia, the mechanisms that govern these changes remain unclear. We hypothesized that aging causes structural remodeling of mitochondrial 3D architecture representative of dysfunction, and this effect is mitigated by exercise. We used serial block-face scanning electron microscopy to image human skeletal tissue samples, followed by manual contour tracing using Amira software for 3D reconstruction and subsequent analysis of mitochondria. We then applied a rigorous in vitro and in vivo exercise regimen during aging. We found that mitochondria became less complex with age. Specifically, mitochondria lost surface area, complexity, and perimeter, indicating age-related declines in ATP synthesis and interaction capacity. Concomitantly, muscle area, exercise capacity, and mitochondrial dynamic proteins showed age-related losses. Exercise stimulation restored mitofusin 2 (MFN2), which we show is required for mitochondrial structure. Furthermore, we show that this pathway is evolutionarily conserved with Marf, the MFN2 ortholog in Drosophila , as Marf knockdown alters mitochondrial morphology and leads to the downregulation of genes regulating mitochondrial processes. Our results define age-related structural changes in mitochondria and further suggest that exercise may mitigate age-related structural decline through modulation of mitofusins.

DOI: https://doi.org/10.1101/2023.11.13.566502
J Hosp Med. 2024 Jan 03.

Rates of diabetic ketoacidosis with empagliflozin use during hospitalization for acute heart failure.

Cheng-Wei Huang, Janet S Lee, Ming-Sum Lee.

There is concern that sodium-glucose cotransporter-2 inhibitors during hospitalization for acute heart failure (aHF) may precipitate diabetic ketoacidosis (DKA). A retrospective study of all hospitalization encounters for aHF defined by a primary HF International Classification of Diseases (ICD)-10 code in 15 Kaiser Permanente Southern California medical centers hospitalized between January 1, 2021 and August 31, 2023 was performed to describe rates of DKA with empagliflozin use. DKA was defined by the presence of either a DKA ICD-10 code or ketoacidosis lab criteria (bicarbonate <18 mmol/L and urine ketone 1+ or more or elevated serum beta-hydroxybutyrate within 12 h) during hospitalization. Among 21,630 hospital encounters (15,518 patients) for aHF, 1678 (8%) had empagliflozin use. There were 2 (0.1%) probable DKA cases in empagliflozin encounters and 15 (0.1%) in nonexposed encounters. These rates were similar when stratified by diabetes status and ejection fraction. Empagliflozin may be safe during aHF hospitalization.

DOI: https://doi.org/10.1002/jhm.13268
Chem Biol Interact. 2024 Jan 03. pii: S0009-2797(24)00001-2. [Epub ahead of print] 110855

Cannabinoids improve mitochondrial function in skeletal muscle of exhaustive exercise training rats by inhibiting mitophagy through the Pink1/Parkin and Bnip3 pathways.

Juncheng Si, Lili Sun, Ying Qin, Lina Peng, Yongshan Gong, Chun Gao, Wenhui Shen, Mengqi Li.

  Cannabidiol (CBD) is a pure natural phytocannabinoid derived from cannabis that has anti-inflammatory, antiapoptotic and antioxidative stress abilities. In recent years, an increasing number of studies have reported the regulatory effect of CBD on skeletal muscle injury induced by exercise, but its mechanism is still unclear. Mitochondria are the main organelles responsible for the energy supply within eukaryotic cells, and their function has been closely linked to cellular health. Moderate exercise improves mitochondrial function, but the excessive exercise has a negative impact on mitochondria. Therefore, we speculate that CBD may promote exercise induced skeletal muscle cell damage by improving mitochondrial function. In this study, by establishing an animal model of exhaustive exercise training in rats, the effects of CBD on the protective effect of CBD on skeletal muscle mitochondrial structure and function was elaborated, and the possible molecular mechanism was discussed based on transcriptomics. Our results indicate that skeletal muscle mitochondrial structure and function were improved after CBD intervention. GO and KEGG pathway enrichment analysis showed that exhaustive exercise training induced mitochondrial dysfunction in skeletal muscle is associated with excessive autophagy/mitophagy, the signaling pathways involved in FOXO3 and GABARAPL1 may play important roles. After CBD intervention, the protein expression of Pink1, Parkin and Bnip3 was down-regulated, indicating that CBD may improve the mitochondrial function by inhibiting mitophagy through the Pink1/Parkin and Bnip3 pathway.

Keywords:  Cannabinoid; Exhaustive exercise; Mitophagy; Skeletal muscle; Transcriptome

DOI:  https://doi.org/10.1016/j.cbi.2024.110855
Diabetol Metab Syndr. 2024 Jan 03. 16(1): 4

Effect of intermittent fasting on lipid biokinetics in obese and overweight patients with type 2 diabetes mellitus: prospective observational study.

Yasmin Atwa Mohamed, Megahed Abouelmagd, Aya Elbialy, Mona Elwassefy, Fady Kyrillos.

   BACKGROUND: Intermittent fasting (IF) is a commonly used dietary practice that alternates between periods of unrestricted dietary consumption and abstinence from caloric intake. IF reduces caloric intake along with metabolic switch from utilization of glucose to fatty acids and ketones and resulting in reduction in adiposity and subsequently insulin resistance. Thus, it has been hypothesized that IF regimens can improve body composition in obese and overweight individuals.
AIM: To assess the effect of IF on lipid biokinetics in obese and overweight patients with type 2 diabetes (T2D).
PATIENTS AND METHODS: Thirty overweight or obese T2D patients were recruited from the diabetes outpatient clinics at the Specialized Medical Hospital, Mansoura University. Patients were subjected to time restricted fasting for 16 h (from dawn to sunset) during Ramadan. Anthropometric data were measured for participants before and 3 weeks after Ramadan fasting. Fasting plasma glucose (FPG), HbA1c, lipid profile, leptin, beta hydroxybutyrate (βHB) and high sensitive CRP levels were measured 1 week before and 3 weeks after Ramadan fasting.
RESULTS: 30 diabetic patients were recruited with a mean age of 54.3 ± 7.2 years. 24 (80%) were females. Obesity was diagnosed in 27 cases (90%). The median diabetes duration was 10 years. The study showed a statistically significant decrease in post-fasting body weight (BW), Body mass index (BMI), waist circumference (WC) & hip circumference (HC). There was a statistically significant decrease of post-fasting low density lipoprotein (LDL-C), Total cholesterol (TC), and leptin. The study also showed a statistically significant increase of post-fasting high density lipoprotein (HDL-C) and βHB. No significant change was found in post-fasting levels of HbA1c, FPG, triglycerides (TG) or high sensitive CRP. Post-fasting leptin was positively correlated with post-fasting BW, BMI, WC, and HC. Post-fasting βHB was positively correlated with post-fasting TG, HbA1c, and LDL-C. Leptin levels change (pre vs post fasting) was positively correlated with the change in LDL-C levels.
CONCLUSION: IF reduced leptin and increased β-hydroxybutyrate levels. IF is an effective tool for losing weight and visceral fat and improving lipid profile in obese and overweight patients with T2D.

Keywords:  Beta hydroxy butyric acid; Intermittent fasting; Leptin; Metabolic switch

DOI:  https://doi.org/10.1186/s13098-023-01234-3
Med Sci Sports Exerc. 2023 Dec 27.

Low Energy Availability Followed by Optimal Energy Availability Does Not Benefit Performance in Trained Females.

Mikkel Oxfeldt, Daniel Marsi, Peter M Christensen, Ole Emil Andersen, Frank Ted Johansen, Maj Bangshaab, Jeyanthini Risikesan, Jan S Jeppesen, Ylva Hellsten, Stuart M Phillips, Anna K Melin, Niels Ørtenblad, Mette Hansen.

PURPOSE: Short periods of reduced energy availability are commonly undertaken by athletes to decrease body mass, possibly improve the power-to-mass ratio, and enhance physical performance. Our primary aim was to investigate the impact of 10 days of low energy availability (LEA) followed by 2 days of optimal energy availability (OEA) on physical performance parameters in trained females. Secondly, physiological markers at the whole-body and molecular level related to performance were evaluated.
METHODS: Thirty young trained eumenorrheic females were matched in pairs based on training history and randomized to a 10-day intervention period of LEA (25 kcal • fat-free mass (FFM)-1 • day-1) or OEA (50 kcal • FFM-1 • day-1) along with supervised exercise training. Before the intervention, participants underwent a 5-day run-in period with OEA + supervised exercise training. Following the LEA intervention, two days of recovery with OEA were completed. Participants underwent muscle biopsies, blood sampling, physical performance tests, body composition measurements, and resting metabolic rate measurements. A linear mixed model was used with group and time as fixed effects and subject as random effects.
RESULTS: Compared to OEA, LEA resulted in reduced body mass, muscle glycogen content, repeated sprint ability, 4-min time trial performance, and rate of force development of the knee extensors (absolute values) (p < 0.05). Two days of recovery restored 4-min time trial performance and partly restored repeated sprint ability, but performance remained inferior to the OEA group. When expressed relative to body mass, LEA did not enhance performance.
CONCLUSIONS: Ten days of LEA resulted in impaired performance (absolute values), with concomitant reductions in muscle glycogen. Two days of recovery with OEA partially restored these impairments, although physical performance (absolute values) was still inferior to being in OEA. Our findings do not support the thesis that LEA giving rise to small reductions in body mass improves the power-to-mass ratio and, thus, increases physical performance.

DOI: https://doi.org/10.1249/MSS.0000000000003370
Curr Pharm Biotechnol. 2024 Jan 01.

Potential Impact of Bioactive Compounds as NLRP3 Inflammasome Inhibitors: An Update.

Sonia Singh, Shiwangi Sharma, Himanshu Sharma.

  The inflammasome NLRP3 comprises a caspase recruitment domain, a pyrin domain containing receptor 3, an apoptosis-linked protein like a speck containing a procaspase-1, and an attached nucleotide domain leucine abundant repeat. There are a wide variety of stimuli that can activate the inflammasome NLRP3. When activated, the protein NLRP3 appoints the adapter protein ASC. Adapter ASC protein then recruits the procaspase-1 protein, which causes the procaspase- 1 protein to be cleaved and activated, which induces cytokines. At the same time, abnormal activation of inflammasome NLRP3 is associated with many diseases, such as diabetes, atherosclerosis, metabolic syndrome, cardiovascular and neurodegenerative diseases. As a result, a significant amount of effort has been put into comprehending the mechanisms behind its activation and looking for their specific inhibitors. In this review, we primarily focused on phytochemicals that inhibit the inflammasome NLRP3, as well as discuss the defects caused by NLRP3 signaling. We conducted an in-depth research review by searching for relevant articles in the Scopus, Google Scholar, and PubMed databases. By gathering information on phytochemical inhibitors that block NLRP3 inflammasome activation, a complicated balance between inflammasome activation or inhibition with NLRP3 as a key role was revealed in NLRP3-driven clinical situations.

Keywords:  NLRP3; apoptosis; bioactive compounds; cytokines; inflammasome

DOI:  https://doi.org/10.2174/0113892010276859231125165251
Front Vet Sci. 2023 ;10 1254340

Diagnostic agreement between three point-of-care glucose and β-hydroxybutyrate meters and reference laboratory methods in stingrays.

Nicholas G Dannemiller, Carolyn Cray, Lori S Westmoreland, Emily F Christiansen.

  Point-of-care (POC) glucose and β-hydroxybutyrate (β-HB) meters can potentially provide rapid insight into an elasmobranch's metabolic state in clinical and field research settings. This study evaluated the diagnostic agreement of three commercial POC meters against reference laboratory methods for glucose and β-HB concentrations in stingrays. Blood was collected during anesthetized exams from 28 stingrays representing four species: cownose rays (Rhinoptera bonasus), Atlantic stingrays (Hypanus sabina), southern stingrays (Hypanus americanus), and yellow stingrays (Urobatis jamaicensis). Glucose and β-HB concentrations were measured with each POC meter using whole blood and plasma; in parallel, plasma glucose and β-HB concentrations were measured via reference laboratory methods. Agreement between POC meters and reference laboratory methods was assessed using Bland-Altman methods, Passing-Bablok regression, observed total error, percent relative error, and linear mixed effect models. Plasma glucose and β-HB concentrations determined by reference laboratory methods ranged from <20-63 mg/dL to 0.05-5.38 mmol/L, respectively. One human POC meter-the Precision Xtra-showed the greatest agreement with reference laboratory methods when measuring glucose with whole blood [mean bias and 95% CI: 0 (-3-4) mg/dL] and β-HB with plasma [mean bias and 95% CI: 0.1 (-0.04-0.2) mmol/L]. Stingray sex, weight, buffy coat, and packed cell volume did not significantly affect the agreement between POC meters and reference laboratory methods. Across all three POC meters, mean bias and imprecision for plasma β-HB concentrations were relatively small (0-0.1 mmol/L and 0%, respectively). Utilizing POC meters to measure glucose and β-HB in stingrays may be viable when reference methods are unavailable.

Keywords:  batoid; clinical pathology; elasmobranch; ketone; metabolism

DOI:  https://doi.org/10.3389/fvets.2023.1254340
Cell Metab. 2024 Jan 02. pii: S1550-4131(23)00446-1. [Epub ahead of print]36(1): 21-35

Mitochondrial-derived vesicles in metabolism, disease, and aging.

Tim König, Heidi M McBride.

Mitochondria are central hubs of cellular metabolism and are tightly connected to signaling pathways. The dynamic plasticity of mitochondria to fuse, divide, and contact other organelles to flux metabolites is central to their function. To ensure bona fide functionality and signaling interconnectivity, diverse molecular mechanisms evolved. An ancient and long-overlooked mechanism is the generation of mitochondrial-derived vesicles (MDVs) that shuttle selected mitochondrial cargoes to target organelles. Just recently, we gained significant insight into the mechanisms and functions of MDV transport, ranging from their role in mitochondrial quality control to immune signaling, thus demonstrating unexpected and diverse physiological aspects of MDV transport. This review highlights the origin of MDVs, their biogenesis, and their cargo selection, with a specific focus on the contribution of MDV transport to signaling across cell and organ barriers. Additionally, the implications of MDVs in peroxisome biogenesis, neurodegeneration, metabolism, aging, and cancer are discussed.

DOI: https://doi.org/10.1016/j.cmet.2023.11.014
Biomed Pharmacother. 2023 Dec 28. pii: S0753-3322(23)01890-5. [Epub ahead of print]170 116092

Macrophage fatty acid oxidation in atherosclerosis.

Sujun Xiao, Mingxu Qi, Qinyi Zhou, Huiqin Gong, Duhui Wei, Guangneng Wang, Qilun Feng, Zhou Wang, Zhe Liu, Yiren Zhou, Xiaofeng Ma.

  Atherosclerosis significantly contributes to the development of cardiovascular diseases (CVD) and is characterized by lipid retention and inflammation within the artery wall. Multiple immune cell types are implicated in the pathogenesis of atherosclerosis, macrophages play a central role as the primary source of inflammatory effectors in this pathogenic process. The metabolic influences of lipids on macrophage function and fatty acid β-oxidation (FAO) have similarly drawn attention due to its relevance as an immunometabolic hub. This review discusses recent findings regarding the impact of mitochondrial-dependent FAO in the phenotype and function of macrophages, as well as transcriptional regulation of FAO within macrophages. Finally, the therapeutic strategy of macrophage FAO in atherosclerosis is highlighted.

Keywords:  Atherosclerosis; Fatty acid oxidation; Macrophage; NLRP3 inflammasome; Peroxisome proliferator-activated receptors

DOI:  https://doi.org/10.1016/j.biopha.2023.116092
Exp Mol Med. 2024 Jan 04.

Mitochondria as secretory organelles and therapeutic cargos.

Joonho Suh, Yun-Sil Lee.

Mitochondria have been primarily considered intracellular organelles that are responsible for generating energy for cell survival. However, accumulating evidence suggests that mitochondria are secreted into the extracellular space under physiological and pathological conditions, and these secreted mitochondria play diverse roles by regulating metabolism, the immune response, or the differentiation/maturation in target cells. Furthermore, increasing amount of research shows the therapeutic effects of local or systemic administration of mitochondria in various disease models. These findings have led to growing interest in exploring mitochondria as potential therapeutic agents. Here, we discuss the emerging roles of mitochondria as extracellularly secreted organelles to shed light on their functions beyond energy production. Additionally, we provide information on therapeutic outcomes of mitochondrial transplantation in animal models of diseases and an update on ongoing clinical trials, underscoring the potential of using mitochondria as a novel therapeutic intervention.

DOI: https://doi.org/10.1038/s12276-023-01141-7