bims-kimdis 2023-12-10 papers

bims-kimdis

Biomed News

on Ketones, inflammation and mitochondria in disease

Issue of 2023–12–10
fourteen papers selected by
Matías Javier Monsalves Álvarez, Universidad de O’Higgins

Ketone bodies in right ventricular failure: A unique therapeutic opportunity.
The effect of a ketogenic diet on weight loss in CKD: a randomized controlled trial in obese stage G1-3a CKD patients.
Skeletal muscle mitochondria demonstrate similar respiration per cristae surface area independent of training status and sex in healthy humans.
Exercise training modifies skeletal muscle clock gene expression but not 24-hour rhythmicity in substrate metabolism of men with insulin resistance.
A High MCT-Based Ketogenic Diet Suppresses Th1 and Th17 Responses to Ameliorate Experimental Autoimmune Encephalomyelitis in Mice by Inhibiting GSDMD and JAK2-STAT3/4 Pathways.
GDF15 is a major determinant of ketogenic diet-induced weight loss.
A Ketone Monoester with Carbohydrate Improves Cognitive Measures Post-Exercise, but not Performance in Trained Females.
Ingestion of triglycerides containing medium- and long-chain fatty acids can increase metabolism of ingested long-chain triglycerides in overweight persons.
The contribution of mitochondria to age-related skeletal muscle wasting: A sex-specific perspective.
NLRP3 inflammasome activation in sensory neurons promotes chronic inflammatory and osteoarthritis pain.
NLRP3 inflammasome pathway, the hidden balance in pregnancy: A comprehensive review.
Resistance Exercise Training in Individuals With and Without Cardiovascular Disease: 2023 Update: A Scientific Statement From the American Heart Association.
Mitochondrial dynamics and metabolism across skin cells: implications for skin homeostasis and aging.
The mitochondrial fission protein DRP1 influences memory CD8+ T cell formation and function.

Heliyon. 2023 Nov;9(11): e22227

Ketone bodies in right ventricular failure: A unique therapeutic opportunity.

Madelyn Blake, Patrycja Puchalska, Felipe Kazmirczak, Jeffrey Blake, Ryan Moon, Thenappan Thenappan, Peter A Crawford, Kurt W Prins.

Background: Ketone bodies are pleotropic metabolites that play important roles in multiple biological processes ranging from bioenergetics to inflammation regulation via suppression of the NLRP3 inflammasome, and epigenetic modifications. Ketone bodies are elevated in left ventricular failure (LVF) and multiple approaches that increase ketone concentrations exert advantageous cardiac effects in rodents and humans. However, the relationships between ketone bodies and right ventricular failure (RVF) are relatively unexplored.
Methods: 51 PAH patients were dichotomized into preserved or impaired RV function based on a cardiac index of 2.2 L/min/m2. Impaired RV function patients were further segmented into intermediate or severe RV dysfunction based on a right atrial pressure of 8 mm Hg. Serum ketone bodies acetoacetate (AcAc) and beta-hydroxybutyrate (βOHB) were quantified using ultra performance liquid chromatography and mass spectrometry. In rodent studies, male Sprague Dawley rats were assigned to three groups: control (saline injection), monocrotaline (MCT) standard chow diet (MCT-Standard), and MCT ketogenic diet (MCT-Keto). Immunoblots and confocal microscopy probed macrophage NLRP3 activation in RV extracts and sections. RV fibrosis was determined by Picrosirus Red. Echocardiography evaluated RV function. Pulmonary arteriole remodeling was assessed from histological specimens.
Results: Human RVF patients lacked a compensatory ketosis as serum AcAc and βOHB levels were not associated with hemodynamic, echocardiographic, or biochemical measures of RV dysfunction. In rodent studies, AcAc and βOHB levels were also not elevated in MCT-mediated RVF, but the ketogenic diet significantly increased AcAc and βOHB levels. MCT-Keto exhibited suppressed NLRP3 activation with a reduction in NLRP3, ASC (apoptosis-associated speck-like protein), pro-caspase-1, and interleukin-1 beta on immunoblots. Moreover, the number of ASC-positive macrophage in RV sections was reduced, RV fibrosis was blunted, and RV function was augmented in MCT-Keto rats.
Conclusion: The ketogenic response is blunted in pulmonary arterial hypertension (PAH) patients with RVF. In the MCT rat model of PAH-mediated RVF, a dietary-induced ketosis improves RV function, suppresses NLRP3 inflammasome activation, and combats RV fibrosis. The summation of these data suggest ketogenic therapies may be particularly efficacious in RVF, and therefore future studies evaluating ketogenic interventions in human RVF are warranted.

DOI: https://doi.org/10.1016/j.heliyon.2023.e22227
Clin Kidney J. 2023 Dec;16(12): 2309-2313

The effect of a ketogenic diet on weight loss in CKD: a randomized controlled trial in obese stage G1-3a CKD patients.

Carmine Zoccali, Vincenzo Bellizzi, Roberto Minutolo, Francesca Mallamaci, Giuseppe Conte, Luca De Nicola.

  This study describes a multicentre randomized controlled trial comparing the effects of a ketogenic diet with a low-energy standard diet containing 0.8 g/kg/day on weight loss and metabolic alterations in adult patients with mild-to-moderate non-diabetic chronic kidney disease (CKD) and mild-to-severe obesity. The study is being conducted to understand the impact of the ketogenic diet on weight loss in these patients, as the existing evidence on the ketogenic diet's effect in CKD patients is limited and inconclusive. The study will enrol mild-to moderate adult CKD patients (Stages G1-3a) with albumin to creatinine ratio ≥200 mg/g, without diabetes, with obesity (body mass index ≥30 kg/m2), and stable body weight and estimated glomerular filtration rate from at least 3 months. The primary outcome will be weight loss at 6 months, and secondary outcomes will include adherence to prescribed dietary regimens, body composition changes, changes in standardized blood pressure measurements, metabolic parameters, lipid profile, liver profile, mineral bone disease biomarkers, and changes in renal function and albuminuria. The findings of this study will contribute to a better understanding of the potential benefits and risks of the ketogenic diet in CKD patients with obesity. The results will help guide future research on the ketogenic diet and renal health.

Keywords:  CKD; dietary proteins; ketogenic diet; low-carbohydrate diet; obesity

DOI:  https://doi.org/10.1093/ckj/sfad176
J Physiol. 2023 Dec 05.

Skeletal muscle mitochondria demonstrate similar respiration per cristae surface area independent of training status and sex in healthy humans.

Camilla Tvede Schytz, Niels Ørtenblad, Anne-Kristine Meinild Lundby, Robert Acton Jacobs, Joachim Nielsen, Carsten Lundby.

  The impact of training status and sex on intrinsic skeletal muscle mitochondrial respiratory capacity remains unclear. We examined this by analysing human skeletal muscle mitochondrial respiration relative to mitochondrial volume and cristae density across training statuses and sexes. Mitochondrial cristae density was estimated in skeletal muscle biopsies originating from previous independent studies. Participants included females (n = 12) and males (n = 41) across training statuses ranging from untrained (UT, n = 8), recreationally active (RA, n = 9), active-to-elite runners (RUN, n = 27) and cross-country skiers (XC, n = 9). The XC and RUN groups demonstrated higher mitochondrial volume density than the RA and UT groups while all active groups (RA, RUN and XC) displayed higher mass-specific capacity of oxidative phosphorylation (OXPHOS) and mitochondrial cristae density than UT. Differences in OXPHOS diminished between active groups and UT when normalising to mitochondrial volume density and were lost when normalising to muscle cristae surface area density. Moreover, active females (n = 6-9) and males (n = 15-18) did not differ in mitochondrial volume and cristae density, OXPHOS, or when normalising OXPHOS to mitochondrial volume density and muscle cristae surface area density. These findings demonstrate: (1) differences in OXPHOS between active and untrained individuals may be explained by both higher mitochondrial volume and cristae density in active individuals, with no difference in intrinsic mitochondrial respiratory capacity (OXPHOS per muscle cristae surface area density); and (2) no sex differences in mitochondrial volume and cristae density or mass-specific and normalised OXPHOS. This highlights the importance of normalising OXPHOS to muscle cristae surface area density when studying skeletal muscle mitochondrial biology. KEY POINTS: Oxidative phosphorylation is the mitochondrial process by which ATP is produced, governed by the electrochemical gradient across the inner mitochondrial membrane with infoldings named cristae. In human skeletal muscle, the mass-specific capacity of oxidative phosphorylation (OXPHOS) can change independently of shifts in mitochondrial volume density, which may be attributed to variations in cristae density. We demonstrate that differences in skeletal muscle OXPHOS between healthy females and males, ranging from untrained to elite endurance athletes, are matched by differences in cristae density. This suggests that higher OXPHOS in skeletal muscles of active individuals is attributable to an increase in the density of cristae. These findings broaden our understanding of the variability in human skeletal muscle OXPHOS and highlight the significance of cristae, specific to mitochondrial respiration.

Keywords:  intrinsic mitochondrial respiratory capacity; mitochondria; mitochondrial cristae density; oxidative phosphorylation; sex; skeletal muscle; training status

DOI:  https://doi.org/10.1113/JP285091
J Physiol. 2023 Dec 05.

Exercise training modifies skeletal muscle clock gene expression but not 24-hour rhythmicity in substrate metabolism of men with insulin resistance.

Jan-Frieder Harmsen, Marit Kotte, Ivo Habets, Frederieke Bosschee, Koen Frenken, Johanna A Jorgensen, Soraya de Kam, Esther Moonen-Kornips, Jochem Cissen, Daniel Doligkeit, Tineke van de Weijer, Edmundo Erazo-Tapia, Mijke Buitinga, Joris Hoeks, Patrick Schrauwen.

  Twenty-four hour rhythmicity in whole-body substrate metabolism, skeletal muscle clock gene expression and mitochondrial respiration is compromised upon insulin resistance. With exercise training known to ameliorate insulin resistance, our objective was to test if exercise training can reinforce diurnal variation in whole-body and skeletal muscle metabolism in men with insulin resistance. In a single-arm longitudinal design, 10 overweight and obese men with insulin resistance performed 12 weeks of high-intensity interval training recurrently in the afternoon (between 14.00 and 18.00 h) and were tested pre- and post-exercise training, while staying in a metabolic research unit for 2 days under free-living conditions with regular meals. On the second days, indirect calorimetry was performed at 08.00, 13.00, 18.00, 23.00 and 04.00 h, muscle biopsies were taken from the vastus lateralis at 08.30, 13.30 and 23.30 h, and blood was drawn at least bi-hourly over 24 h. Participants did not lose body weight over 12 weeks, but improved body composition and exercise capacity. Exercise training resulted in reduced 24-h plasma glucose levels, but did not modify free fatty acid and triacylglycerol levels. Diurnal variation of muscle clock gene expression was modified by exercise training with period genes showing an interaction (time × exercise) effect and reduced mRNA levels at 13.00 h. Exercise training increased mitochondrial respiration without inducing diurnal variation. Twenty-four-hour substrate metabolism and energy expenditure remained unchanged. Future studies should investigate alternative exercise strategies or types of interventions (e.g. diet or drugs aiming at improving insulin sensitivity) for their capacity to reinforce diurnal variation in substrate metabolism and mitochondrial respiration. KEY POINTS: Insulin resistance is associated with blunted 24-h flexibility in whole-body substrate metabolism and skeletal muscle mitochondrial respiration, and disruptions in the skeletal muscle molecular circadian clock. We hypothesized that exercise training modifies 24-h rhythmicity in whole-body substrate metabolism and diurnal variation in skeletal muscle molecular clock and mitochondrial respiration in men with insulin resistance. We found that metabolic inflexibility over 24 h persisted after exercise training, whereas mitochondrial respiration increased independent of time of day. Gene expression of Per1-3 and Rorα in skeletal muscle changed particularly close to the time of day at which exercise training was performed. These results provide the rationale to further investigate the differential metabolic impact of differently timed exercise to treat metabolic defects of insulin resistance that manifest at a particular time of day.

Keywords:  circadian rhythm; exercise; insulin resistance; mitochondria

DOI:  https://doi.org/10.1113/JP285523
Mol Nutr Food Res. 2023 Dec 06. e2300602

A High MCT-Based Ketogenic Diet Suppresses Th1 and Th17 Responses to Ameliorate Experimental Autoimmune Encephalomyelitis in Mice by Inhibiting GSDMD and JAK2-STAT3/4 Pathways.

Qianye Zhang, Wei Sun, Qingpeng Wang, Xuexing Zheng, Ruiyan Zhang, Ning Zhang.

   SCOPE: Inflammation and pyroptosis play important roles in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In this study, we evaluated the therapeutic potential of ketogenic diet (KD) in EAE.
METHODS AND RESULTS: The administration of KD reduces demyelination and microglial activation in the spinal cord of EAE mice. Meanwhile, KD decreases the levels of Th1 and Th17 associated cytokines/transcription factors production (T-bet, IFN-γ, RORγt, and IL-17) and increases those of Th2 and Treg cytokines/transcription factors (GATA3, IL-4, Foxp3, and IL-10) in the spinal cord and spleen. Corresponding, KD reduces the expression of chemokines in EAE, which those chemokines associate with T-cell infiltration into central nervous system (CNS). In addition, KD inhibits the GSDMD activation in microglia, oligodendrocyte, CD31+ cells, CCR2+ cells, and T cells in the spinal cord. Moreover, KD significantly decreases the ratios of p-JAK2/JAK2, p-STAT3/STAT3, and p-STAT4/STAT4, as well as GSDMD in EAE mice.
CONCLUSIONS: this study demonstrates that KD reduces the activation and differentiation of T cells in the spinal cord and spleen and prevents T cell infiltration into CNS of EAE via modulating the GSDMD and STAT3/4 pathways, suggesting that KD is a potentially effective strategy in the treatment of MS.

Keywords:  T cell; demyelination; experimental autoimmune encephalomyelitis; gasdermin D; ketogenic diet; multiple sclerosis

DOI:  https://doi.org/10.1002/mnfr.202300602
Cell Metab. 2023 Dec 05. pii: S1550-4131(23)00414-X. [Epub ahead of print]35(12): 2165-2182.e7

GDF15 is a major determinant of ketogenic diet-induced weight loss.

Jun Feng Lu, Meng Qing Zhu, Bo Xia, Na Na Zhang, Xiao Peng Liu, Huan Liu, Rui Xin Zhang, Jun Ying Xiao, Hui Yang, Ying Qi Zhang, Xiao Miao Li, Jiang Wei Wu.

  A ketogenic diet (KD) has been promoted as an obesity management diet, yet its underlying mechanism remains elusive. Here we show that KD reduces energy intake and body weight in humans, pigs, and mice, accompanied by elevated circulating growth differentiation factor 15 (GDF15). In GDF15- or its receptor GFRAL-deficient mice, these effects of KD disappeared, demonstrating an essential role of GDF15-GFRAL signaling in KD-mediated weight loss. Gdf15 mRNA level increases in hepatocytes upon KD feeding, and knockdown of Gdf15 by AAV8 abrogated the obesity management effect of KD in mice, corroborating a hepatic origin of GDF15 production. We show that KD activates hepatic PPARγ, which directly binds to the regulatory region of Gdf15, increasing its transcription and production. Hepatic Pparγ-knockout mice show low levels of plasma GDF15 and significantly diminished obesity management effects of KD, which could be restored by either hepatic Gdf15 overexpression or recombinant GDF15 administration. Collectively, our study reveals a previously unexplored GDF15-dependent mechanism underlying KD-mediated obesity management.

Keywords:  GDF15; GFRAL; hepatic PPARγ; ketogenic diet; obesity

DOI:  https://doi.org/10.1016/j.cmet.2023.11.003
Med Sci Sports Exerc. 2023 Nov 23.

A Ketone Monoester with Carbohydrate Improves Cognitive Measures Post-Exercise, but not Performance in Trained Females.

Hunter S Waldman, Eric K O'Neal, Gaven A Barker, Craig R Witt, David A Lara, Anna K Huber, Valerie N Forsythe, Andrew P Koutnik, Dominic P D'Agostino, Walter Staiano, Brendan Egan.

PURPOSE: Acute ingestion of a ketone monoester with co-ingestion of a carbohydrate (KME + CHO) compared to carbohydrate (CHO) was investigated on cycling performance and cognitive performance in trained females.
METHODS: Using a two condition, placebo-controlled, double-blinded and crossover design, twelve trained females (mean ± SD: age, 23 ± 3 y; height, 1.64 ± 0.08 m; mass, 65.2 ± 12.7 kg) completed a baseline assessment of cognitive performance (psychomotor vigilance testing (PVT), task switching, and incongruent flanker), followed by 6x5-min intervals at 40%, 45%, 50%, 55%, 60%, and 65% of their maximal power output (Wmax) and then a 10-km time trial (TT), concluding with the same assessments of cognitive performance. Participants consumed either 375 mg·kg-1 body mass of KME with a 6% CHO solution (1 g·min-1 of exercise) or CHO alone, across 3 boluses (50:25:25).
RESULTS: Blood β-hydroxybutyrate concentrations averaged 1.80 ± 0.07 mM and 0.13 ± 0.01 mM during exercise in KME + CHO and CHO, respectively. Blood glucose decreased following drink 1 of KME + CHO (~15%; P = 0.01) but not CHO, and lactate concentrations were lower in KME + CHO at 50%, 55%, 60%, and 65%Wmax (all P < 0.05), compared to CHO. Despite these changes, no differences were found between conditions for TT finishing times (KME + CHO, 29.7 ± 5.7 min; CHO, 29.6 ± 5.7 min; P = 0.92). However, only KME + CHO resulted in increases in PVT speed (~4%; P = 0.01), and faster reaction times (~14%; P < 0.01), speed (~15%; P < 0.01), and correct responses (~13%; P = 0.03) in the incongruent flanker during post-testing compared to CHO.
CONCLUSIONS: Acute ingestion of a KME + CHO elevated blood β-hydroxybutyrate and lowered glucose and lactate across multiple timepoints during exercise compared to CHO. Although these changes did not affect physical performance, several markers of cognitive performance were improved by the addition of a KME in trained females.

DOI: https://doi.org/10.1249/MSS.0000000000003352
Front Nutr. 2023 ;10 1260506

Ingestion of triglycerides containing medium- and long-chain fatty acids can increase metabolism of ingested long-chain triglycerides in overweight persons.

Naohisa Nosaka, Shogo Tsujino, Shohei Sadamitsu, Nanaka Ando, Kazuhiko Kato.

   Introduction: Medium-chain fatty acids (MCFAs) have attracted considerable attention for preventing or improving obesity, which is a recognized risk factor for lifestyle-related diseases. Medium- and long-chain triglycerides (MLCTs) are expected to improve the metabolism of ingested long-chain triglycerides (LCTs). However, previous studies have reported mixed results. In this study, the effect of ingestion of MLCTs was evaluated on the metabolism of LCTs and compared to the ingestion of rapeseed oil (control oil).
Methods: A randomized, double-blind, placebo-controlled crossover study was performed among sedentary participants with BMIs ranging from 25 below 30 kg/m2. Thirty participants were asked to ingest either 14 g of MLCTs or a control oil for 4 weeks. The metabolism of ingested LCTs was evaluated by measuring isotopically labeled carbon dioxide released by the degradation of carbon-13 (13C)-labeled LCTs.
Results: Ingestion of MLCTs markedly enhanced the metabolism of ingested LCTs by comparison to the control oil.
Conclusion: The findings of this study suggest that ingestion of MLCTs may enhance the metabolism of dietary LCTs through activation of β-oxidation in liver mitochondria, which may increase the metabolic kinetics of ingested long-chain fatty acid (LCFAs).
Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000053101, identifier: UMIN000046604.

Keywords:  medium- and long-chain triglycerides; medium-chain fatty acid; metabolism of ingested fat; obesity; postprandial metabolism

DOI:  https://doi.org/10.3389/fnut.2023.1260506
Life Sci. 2023 Nov 30. pii: S0024-3205(23)00959-1. [Epub ahead of print]336 122324

The contribution of mitochondria to age-related skeletal muscle wasting: A sex-specific perspective.

Alessandro Nuccio, Rita Nogueira-Ferreira, Alexandra Moreira-Pais, Alessandro Attanzio, José Alberto Duarte, Claudio Luparello, Rita Ferreira.

  As people age, their skeletal muscle (SkM) experiences a decline in mitochondrial functionality and density, which leads to decreased energy production and increased generation of reactive oxygen species. This cascade of events, in turn, might determine the loss of SkM mass, strength and quality. Even though the mitochondrial processes dysregulated by aging, such as oxidative phosphorylation, mitophagy, antioxidant defenses and mtDNA transcription, are the same in both sexes, mitochondria age differently in the SkM of men and women. Indeed, the onset and magnitude of the impairment of these processes seem to be influenced by sex-specific factors. Sexual hormones play a pivotal role in the regulation of SkM mass through both genomic and non-genomic mechanisms. However, the precise mechanisms by which these hormones regulate mitochondrial plasticity in SkM are not fully understood. Although the presence of estrogen receptors in mitochondria is recognized, it remains unclear whether androgen receptors affect mitochondrial function. This comprehensive review critically dissects the current knowledge on the interplay of sex in the aging of SkM, focusing on the role of sex hormones and the corresponding signaling pathways in shaping mitochondrial plasticity. Improved knowledge on the sex dimorphism of mitochondrial aging may lead to sex-tailored interventions that target mitochondrial health, which could be effective in slowing or preventing age-related muscle loss.

Keywords:  Androgens; Estrogens; Mitochondria remodeling; Sarcopenia; Sexual dimorphism

DOI:  https://doi.org/10.1016/j.lfs.2023.122324
Immunother Adv. 2023 ;3(1): ltad022

NLRP3 inflammasome activation in sensory neurons promotes chronic inflammatory and osteoarthritis pain.

Patrícia Silva Santos Ribeiro, Hanneke L D M Willemen, Sabine Versteeg, Christian Martin Gil, Niels Eijkelkamp.

  Pain is one of the most debilitating symptoms in rheumatic diseases. Pain often persists after total knee replacement in osteoarthritis, or when inflammation is minimal/absent in rheumatoid arthritis. This suggests that pain transitions to a chronic state independent of the original damage/inflammation. Mitochondrial dysfunction in the nervous system promotes chronic pain and is linked to NLRP3 inflammasome activation. Therefore, we investigated the role of mitochondrial dysfunction and NLRP3 inflammasome activation in the transition from acute to persistent inflammation-induced nociplastic pain and in persistent monoiodoacetate-induced osteoarthritis pain. Intraplantar injection of carrageenan in mice induced transient inflammatory pain that resolved within 7 days. A subsequent intraplantar PGE2 injection induced persistent mechanical hypersensitivity, while in naive mice it resolved within one day. Thus, this initial transient inflammation induced maladaptive nociceptor neuroplasticity, so-called hyperalgesic priming. At Day 7, when mice were primed, expression of NLRP3 inflammasome pathway components was increased, and dorsal root ganglia (DRG) neurons displayed signs of activated NLRP3 inflammasome. Inhibition of NLRP3 inflammasome with MCC950 prevented the transition from acute to chronic pain in this hyperalgesic priming model. In mice with persistent monoiodoacetate-induced osteoarthritis pain, DRG neurons displayed signs of mitochondrial oxidative stress and NLRP3 inflammasome activation. Blocking NLRP3 inflammasome activity attenuated established osteoarthritis pain. In males, NLPR3 inhibition had longer-lasting effects than in females. Overall, these data suggest that NLRP3 inflammasome activation in sensory neurons, potentially caused by neuronal oxidative stress, promotes development of persistent inflammatory and osteoarthritis pain. Therefore, targeting NLRP3 inflammasome pathway may be a promising approach to treat chronic pain.

Keywords:  NLRP3 inflammasome; chronic pain; hyperalgesic priming; mitochondrial dysfunction; osteoarthritis; sensory neurons

DOI:  https://doi.org/10.1093/immadv/ltad022
J Reprod Immunol. 2023 Nov 28. pii: S0165-0378(23)00379-0. [Epub ahead of print]161 104173

NLRP3 inflammasome pathway, the hidden balance in pregnancy: A comprehensive review.

Cemre Nur Balci, Nuray Acar.

  The balance of the inflammatory response is indispensable during pregnancy. Inflammasomes are the cytosolic supramolecular protein complexes activated by pattern recognition receptors. These receptors recognize the pathogen and damage/danger-associated molecular patterns. NLRP3 inflammasome complex consists mainly of NLRP3 (leucine-rich repeat-containing and pyrin domain-containing protein 3), a cytosolic sensor molecule, ASC (apoptosis-associated speck-like protein containing a CARD) protein and a cysteine protease pro-caspase-1 as an effector molecule. This complex has a role in producing inflammatory cytokines, interleukin 1 beta and interleukin 18, and inflammasome-dependent programmed cell death pathway pyroptosis. In this review, we focused on and summarised the NLRP3 inflammasome and its roles in normal and pathological pregnancies. The NLRP3 inflammasome pathway influences endometrial receptivity and embryo invasion by inducing epithelial-mesenchymal transition. Abnormal inflammasome activation in the endometrium may adversely affect endometrial receptivity. In addition, NLRP3 inflammasome pathway overactivation may mediate the abnormal inflammatory response at the maternal-fetal interface and be associated with pregnancy complications, such as recurrent implantation failure, pregnancy loss, pre-term birth and pre-eclampsia. Therefore, targeting the NLRP3 inflammasome pathway could develop a new therapeutic approach to prevent the aforementioned pregnancy pathologies.

Keywords:  Decidualization; Embryo implantation; Inflammasome; NLRP3; Pathologic pregnancy

DOI:  https://doi.org/10.1016/j.jri.2023.104173
Circulation. 2023 Dec 07.

Resistance Exercise Training in Individuals With and Without Cardiovascular Disease: 2023 Update: A Scientific Statement From the American Heart Association.

on behalf the American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Peripheral Vascular Disease

  Resistance training not only can improve or maintain muscle mass and strength, but also has favorable physiological and clinical effects on cardiovascular disease and risk factors. This scientific statement is an update of the previous (2007) American Heart Association scientific statement regarding resistance training and cardiovascular disease. Since 2007, accumulating evidence suggests resistance training is a safe and effective approach for improving cardiovascular health in adults with and without cardiovascular disease. This scientific statement summarizes the benefits of resistance training alone or in combination with aerobic training for improving traditional and nontraditional cardiovascular disease risk factors. We also address the utility of resistance training for promoting cardiovascular health in varied healthy and clinical populations. Because less than one-third of US adults report participating in the recommended 2 days per week of resistance training activities, this scientific statement provides practical strategies for the promotion and prescription of resistance training.

Keywords:  AHA Scientific Statements; cardiovascular diseases; exercise; resistance training; risk factors

DOI:  https://doi.org/10.1161/CIR.0000000000001189
Front Physiol. 2023 ;14 1284410

Mitochondrial dynamics and metabolism across skin cells: implications for skin homeostasis and aging.

Ines Martic, Federica Papaccio, Barbara Bellei, Maria Cavinato.

  Aging of human skin is a complex process leading to a decline in homeostasis and regenerative potential of this tissue. Mitochondria are important cell organelles that have a crucial role in several cellular mechanisms such as energy production and free radical maintenance. However, mitochondrial metabolism as well as processes of mitochondrial dynamics, biogenesis, and degradation varies considerably among the different types of cells that populate the skin. Disturbed mitochondrial function is known to promote aging and inflammation of the skin, leading to impairment of physiological skin function and the onset of skin pathologies. In this review, we discuss the essential role of mitochondria in different skin cell types and how impairment of mitochondrial morphology, physiology, and metabolism in each of these cellular compartments of the skin contributes to the process of skin aging.

Keywords:  aging; mitochondria; skin; skin cells; skin homeostasis

DOI:  https://doi.org/10.3389/fphys.2023.1284410
J Leukoc Biol. 2023 Dec 06. pii: qiad155. [Epub ahead of print]

The mitochondrial fission protein DRP1 influences memory CD8+ T cell formation and function.

Marissa G Stevens, Frank M Mason, Timothy N J Bullock.

  Pharmacological methods for promoting mitochondrial elongation suggest that effector T cells can be altered to support a memory T cell-like metabolic state. Such mitochondrial elongation approaches may enhance the development of immunological memory. Therefore, we hypothesized that deletion of the mitochondrial fission protein, DRP1, would lead to mitochondrial elongation and generate a large memory T cell population, an approach that could be exploited to enhance vaccination protocols. We find that, as expected, while deletion of DRP1 from T cells in dLckCre x Drp1flfl does compromise the magnitude and functionality of primary effector CD8+ T cells, a disproportionately large pool of memory CD8+ T cells does form. In contrast to primary effector CD8+ T cells, DRP1-deficient memory dLckCre x Drp1flfl CD8+ T cells mount a secondary response comparable to control memory T cells with respect to kinetics, magnitude, and effector capabilities. Interestingly, the relative propensity to form memory cells in the absence of DRP1 was neither associated with differentiation toward more memory precursor CD8+ T cells nor decreased cellular death of effector T cells. Instead, the tendency to form memory CD8+ T cells in the absence of DRP1 is associated with decreased TCR expression. Remarkably, in a competitive environment with DRP1-replete CD8+ T cells, the absence of DRP1 from CD8+ T cells compromised the generation of primary, memory and secondary responses, indicating that approaches targeting DRP1 need to be carefully tailored.

Keywords:  CD8+ T cell; Cell Death; Cytokine; Differentiation; Memory T cell; Metabolism; Mitochondria; T cell receptor

DOI:  https://doi.org/10.1093/jleuko/qiad155