bims-kimdis 2023-11-05 papers

bims-kimdis

Biomed News

on Ketones, inflammation and mitochondria in disease

Issue of 2023–11–05
fourteen papers selected by
Matías Javier Monsalves Álvarez, Universidad de O’Higgins

Very low-calorie ketogenic diet in the treatment of adaptive thermogenesis: A case report.
Effects of a two meals-a-day ketogenic diet on newly diagnosed obese patients with type 2 diabetes mellitus: A retrospective observational study.
The influence of skeletal muscle mitochondria and sex on critical torque and performance fatiguability in humans.
Actovegin improves skeletal muscle mitochondrial respiration and functional aerobic capacity in a type 1 diabetic male murine model.
Mitochondrial complexome and import network.
Mitochondria makeover: unlocking the path to healthy longevity.
Measurements of In Vivo Skeletal Muscle Oxidative Capacity Are Lower Following Sustained Isometric Compared with Dynamic Contractions.
Influence of aging, mitochondrial dysfunction, and inflammation on Parkinson's disease.
Mitochondrial regulation in stem cells.
The allometry of mitochondrial efficiency is tissue-dependent: A comparison between skeletal and cardiac muscles of birds.
A practical perspective on how to develop, implement, execute, and reproduce high-resolution respirometry experiments: The physiologist's guide to an Oroboros O2k.
Managing Obesity in Heart Failure: A Chance to Tip the Scales?
The effect of sodium-glucose cotransporter 2 inhibitors as an adjunct to insulin in patients with type 1 diabetes assessed by continuous glucose monitoring: A systematic review and meta-analysis.
Applied high-intensity interval cardio yoga improves cardiometabolic fitness, energetic contributions, and metabolic flexibility in healthy adults.

Nutrition. 2023 Oct 01. pii: S0899-9007(23)00280-0. [Epub ahead of print]117 112252

Very low-calorie ketogenic diet in the treatment of adaptive thermogenesis: A case report.

Jônatas de Oliveira, Isis de Carvalho Stelmo, Leandro Silva Figueredo, Carolina Cristina de Freitas.

   OBJECTIVES: The management of the phenomenon of adaptive thermogenesis poses a challenge to the successful treatment of overweight/obesity with a nutritional intervention that minimizes the loss of muscle mass, with little cognitive restraint use and disorganization of eating behavior. On the other hand, it creates a significant calorie deficit for the reduction of body fat. The aim of this case report was to discuss the effects of a very low-calorie ketogenic diet in a woman with obesity and low resting metabolic rate.
CASE DESCRIPTION: A 36-y-old white woman with a history of obesity and bulimia nervosa who has had difficulty losing and maintaining weight despite numerous dietary and pharmacologic treatments.
RESULTS: There was a loss of 12 kg in 115 d, reaching 13.4 kg, with 11.4 kg of fat mass (FM). The resting metabolic rate showed an increase of 79% in relation to the initial rate, reaching normal levels for the predictive equations and maintaining this level in the first-year follow-up. Additionally, improvement of metabolic laboratory parameters and eating behavior traits were described.
CONCLUSIONS: In this specific case of bulimia nervosa resulting in hypometabolism (low resting metabolic rate/fat-free mass) and obesity, the very low-calorie ketogenic diet intervention has demonstrated a possibility of weight loss with little cognitive restraint use, thereby increasing resting metabolic rate in the short and medium terms, ultimately promoting a negative energy balance. In relation to the numeric results, it seems positive; however, more research is necessary to evaluate the effects on the overall relationship with food and its long-term repercussions.

Keywords:  Adaptive thermogenesis; Bulimia nervosa; Eating behavior; Obesity; Resting metabolic rate; Very low-calorie ketogenic diet

DOI:  https://doi.org/10.1016/j.nut.2023.112252
Medicine (Baltimore). 2023 Oct 27. 102(43): e35753

Effects of a two meals-a-day ketogenic diet on newly diagnosed obese patients with type 2 diabetes mellitus: A retrospective observational study.

Sumei Li, Shouping Yuan, Guoxin Lin, Jintian Zhang.

To investigate the effects of a two-meals-a-day energy-restricted ketogenic diet (KD) on newly diagnosed obese patients with type 2 diabetes mellitus. In total, 60 obese patients with newly diagnosed type 2 diabetes mellitus were divided into 2 groups: 1 group followed a 2-meals-a-day KD and the other group followed a conventional diabetic diet. Changes in weight, blood glucose, blood lipids, insulin resistance, and uric acid levels were observed before and after 2 months of adhering to the respective diets under energy restriction. Both groups showed significant reductions in weight, waist circumference, body mass index, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, fasting blood glucose, fasting insulin, and glycated hemoglobin (P < .05). The twice-daily KD group showed more significant improvements in these parameters compared to the conventional diabetic diet group. In addition, the 2-meals-a-day KD group showed a slight increase in uric acid levels compared to the conventional diabetic diet control group (P < .05). The 2-meals-a-day KD can significantly improve weight, blood glucose, and lipid control in newly diagnosed obese patients with type 2 diabetes mellitus.

DOI: https://doi.org/10.1097/MD.0000000000035753
J Physiol. 2023 Oct 30.

The influence of skeletal muscle mitochondria and sex on critical torque and performance fatiguability in humans.

Rachel M McDougall, Thomas R Tripp, Barnaby P Frankish, Patricia K Doyle-Baker, Victor Lun, J Preston Wiley, S Jalal Aboodarda, Martin J MacInnis.

  Critical torque (CT) represents the highest oxidative steady state for intermittent knee extensor exercise, but the extent to which it is influenced by skeletal muscle mitochondria and sex is unclear. Vastus lateralis muscle biopsy samples were collected from 12 females and 12 males -matched for relative maximal oxygen uptake normalized to fat-free mass (FFM) (F: 57.3 (7.5) ml (kg FFM)-1 min-1 ; M: 56.8 (7.6) ml (kg FFM)-1 min-1 ; P = 0.856) - prior to CT determination and performance fatiguability trials. Males had a lower proportion of myosin heavy chain (MHC) I isoform (40.6 (18.4)%) compared to females (59.5 (18.9)%; P = 0.021), but MHC IIa and IIx isoform distributions and protein markers of mitochondrial content were not different between sexes (P > 0.05). When normalized to maximum voluntary contraction (MVC), the relative CT (F: 42.9 (8.3)%; M: 37.9 (9.0)%; P = 0.172) and curvature constant, W' (F: 26.6 (11.0) N m s (N m)-1 ; M: 26.4 (6.5) N m s (N m)-1 ; P = 0.962) were not significantly different between sexes. All protein biomarkers of skeletal muscle mitochondrial content, as well as the proportion of MHC I isoform, positively correlated with relative CT (0.48 < r < 0.70; P < 0.05), and the proportion of MHC IIx isoform correlated positively with relative W' (r = 0.57; P = 0.007). Indices of performance fatiguability were not different between males and females for MVC- and CT-controlled trials (P > 0.05). Greater mitochondrial protein abundance was associated with attenuated declines in potentiated twitch torque for exercise at 60% MVC (P < 0.05); however, the influence of mitochondrial protein abundance on performance fatiguability was reduced when exercise was prescribed relative to CT. Whether these findings translate to whole-body exercise requires additional research. KEY POINTS: The quadriceps critical torque represents the highest intensity of intermittent knee extensor exercise for which an oxidative steady state is attainable, but its relationship with skeletal muscle mitochondrial protein abundance is unknown. Matching males and females for maximal oxygen uptake relative to fat-free mass facilitates investigations of sex differences in exercise physiology, but studies that have compared critical torque and performance fatiguability during intermittent knee extensor exercise have not ensured equal aerobic fitness between sexes. Skeletal muscle mitochondrial protein abundance was correlated with critical torque and fatigue resistance for exercise prescribed relative to maximum voluntary contraction but not for exercise performed relative to the critical torque. Differences between sexes in critical torque, skeletal muscle mitochondrial protein abundance and performance fatiguability were not statistically significant. Our results suggest that skeletal muscle mitochondrial protein abundance may contribute to fatigue resistance by influencing the critical intensity of exercise.

Keywords:  aerobic fitness; critical intensity; exercise; exercise prescription; fatigue; quadriceps; sex differences; small muscle mass

DOI:  https://doi.org/10.1113/JP284958
Appl Physiol Nutr Metab. 2023 Nov 01.

Actovegin improves skeletal muscle mitochondrial respiration and functional aerobic capacity in a type 1 diabetic male murine model.

Brandon Kosik, Steen Larsen, Andreas Bergdahl.

Insulin deficiency in type 1 diabetes (T1D) leads to an impairment of glucose metabolism and mitochondrial function. Actovegin is a hemodialysate of calf blood which has been shown to enhance glucose uptake and cell metabolism in healthy human skeletal muscle. The objectives of this study were to determine the effects of Actovegin on skeletal muscle mitochondrial respiration and functional aerobic capacity in a T1D mouse model. Effects on expression of mitochondrial proteins, body mass, food and water consumption were also investigated. Streptozotocin-induced T1D male C57B1/6 mice (aged 3-4 months) were randomized to an Actovegin and a control group. Every third day, the Actovegin and control group were injected intraperitoneally with (0.1 ml) Actovegin and (0.1 ml) physiological salt solution, respectively. Oxidative phosphorylation (OXPHOS) capacity of the vastus lateralis muscle was measured by high resolution respirometry in addition to the expression levels of the mitochondrial complexes as well as voltage dependent anion channel. Functional aerobic capacity was measured using a rodent treadmill protocol. Body mass, food and water consumption were also measured. After 13 days, in comparison to the control group, the Actovegin group demonstrated a significantly higher skeletal muscle mitochondrial respiratory capacity in an ADP-restricted and ADP-stimulated environment. The Actovegin group displayed a significantly lesser decline in functional aerobic capacity and baseline body mass after 13 days. There were no significant differences in food or water consumption between groups. Actovegin could act as an effective agent for facilitating glucose metabolism and improving OXPHOS capacity and functional aerobic capacity in T1D. Further investigation is warranted to establish Actovegin's potential as an alternative therapeutic drug for T1D.

DOI: https://doi.org/10.1139/apnm-2023-0004
Trends Cell Biol. 2023 Oct 30. pii: S0962-8924(23)00208-8. [Epub ahead of print]

Mitochondrial complexome and import network.

Fabian den Brave, Uwe Schulte, Bernd Fakler, Nikolaus Pfanner, Thomas Becker.

  Mitochondria perform crucial functions in cellular metabolism, protein and lipid biogenesis, quality control, and signaling. The systematic analysis of protein complexes and interaction networks provided exciting insights into the structural and functional organization of mitochondria. Most mitochondrial proteins do not act as independent units, but are interconnected by stable or dynamic protein-protein interactions. Protein translocases are responsible for importing precursor proteins into mitochondria and form central elements of several protein interaction networks. These networks include molecular chaperones and quality control factors, metabolite channels and respiratory chain complexes, and membrane and organellar contact sites. Protein translocases link the distinct networks into an overarching network, the mitochondrial import network (MitimNet), to coordinate biogenesis, membrane organization and function of mitochondria.

Keywords:  cell organelles; energetics; metabolism; mitochondria; morphology; protein assembly; protein networks; protein sorting

DOI:  https://doi.org/10.1016/j.tcb.2023.10.004
Expert Opin Ther Targets. 2023 Oct 30. 1-4

Mitochondria makeover: unlocking the path to healthy longevity.

Andrés Caicedo, Keshav K Singh.



Keywords:  Aging; Extracellular Mitochondria; Hallmarks of Aging; Health; Healthy Longevity; Induced Pluripotent Stem Cells (iPSCs); Longevity; Mitochondria; Mitochondrial DNA (mtDNA); Mitochondrial Transfer; Mitochondrial Transplant; Rejuvenation; Senescent Cells; Telomeres

DOI:  https://doi.org/10.1080/14728222.2023.2277240
Appl Physiol Nutr Metab. 2023 Oct 31.

Measurements of In Vivo Skeletal Muscle Oxidative Capacity Are Lower Following Sustained Isometric Compared with Dynamic Contractions.

Miles F Bartlett, Liam F Fitzgerald, Rajakumar Nagarajan, Jane A Kent.

Human skeletal muscle oxidative capacity can be quantified non-invasively using 31-phosphorus magnetic resonance spectroscopy (31P-MRS) to measure the rate constant of phosphocreatine (PCr) recovery (kPCr) following contractions. In the quadricep muscles, several studies have quantified kPCr following 24-30 s of sustained maximal voluntary isometric contraction (MVIC). This approach has the advantage of simplicity but is potentially problematic because sustained MVICs inhibit perfusion, which may limit muscle oxygen availability or increase the intracellular metabolic perturbation, and thus affect kPCr. Alternatively, dynamic contractions allow reperfusion between contractions, which may avoid limitations in oxygen delivery. To determine whether dynamic contraction protocols elicit greater kPCr than sustained MVIC protocols, we used a cross-sectional design to compare quadriceps kPCr in 22 young and 11 older healthy adults following 24s of maximal voluntary: 1) sustained MVIC, and 2) dynamic (MVDC; 120°·s-1, 1 every 2 s) contractions. Muscle kPCr was ∽20% lower following the MVIC protocol compared with the MVDC protocol (p≤0.001), though this was less evident in older adults (p=0.073). Changes in skeletal muscle pH (p≤0.001) and PME accumulation (p≤0.001) were greater following the sustained MVIC protocol, and pH (p≤0.001) and PME (p≤0.001) recovery were slower. These results demonstrate that: 1) a brief, sustained MVIC yields a lower value for skeletal muscle oxidative capacity than an MVDC protocol of similar duration, and 2) this difference may not be consistent across populations (e.g., young vs. old). Thus, the potential effect of contraction protocol on comparisons of kPCr in different study groups requires careful consideration in the future.

DOI: https://doi.org/10.1139/apnm-2023-0315
Neural Regen Res. 2024 Jun 01. 19(6): 1197-1198

Influence of aging, mitochondrial dysfunction, and inflammation on Parkinson's disease.

Davide Cossu, Nobutaka Hattori.

DOI: https://doi.org/10.4103/1673-5374.385873
Trends Cell Biol. 2023 Oct 31. pii: S0962-8924(23)00207-6. [Epub ahead of print]

Mitochondrial regulation in stem cells.

Yifei Wang, Marine Barthez, Danica Chen.

  Stem cells persist throughout the lifespan to repair and regenerate tissues due to their unique ability to self-renew and differentiate. Here we reflect on the recent discoveries in stem cells that highlight a mitochondrial metabolic checkpoint at the restriction point of the stem cell cycle. Mitochondrial activation supports stem cell proliferation and differentiation by providing energy supply and metabolites as signaling molecules. Concomitant mitochondrial stress can lead to loss of stem cell self-renewal and requires the surveillance of various mitochondrial quality control mechanisms. During aging, a mitochondrial protective program mediated by several sirtuins becomes dysregulated and can be targeted to reverse stem cell aging and tissue degeneration, giving hope for targeting the mitochondrial metabolic checkpoint for treating tissue degenerative diseases.

Keywords:  NAD; NLRP3; SIRT2; SIRT3; SIRT7; aging

DOI:  https://doi.org/10.1016/j.tcb.2023.10.003
J Exp Biol. 2023 Nov 03. pii: jeb.246299. [Epub ahead of print]

The allometry of mitochondrial efficiency is tissue-dependent: A comparison between skeletal and cardiac muscles of birds.

Jessica Barbe, Julia Watson, Damien Roussel, Yann Voituron.

  Body mass is known to be a fundamental driver of many biological traits, including metabolism. However, the effect of body mass on mitochondrial energy transduction is still poorly understood and has mainly been described in mammals. Using 13 species of birds ranging from 15 g (finches) to 160 kg (ostrich), we report here that the mitochondrial production of ATP, and corresponding oxygen consumption are negatively dependent on body mass in skeletal muscles but not in the heart. Results also showed that mitochondrial efficiency was positively correlated to body mass at sub-maximal phosphorylating states in the skeletal muscle, but not in the heart. This difference between muscle tissues is potentially linked to the difference in energetic demand expandability and the heavy involvement of skeletal muscle in thermoregulation.

Keywords:  ATP/O; Bioenergetics; Body mass; Endotherms; Metabolic scope; Phylogeny

DOI:  https://doi.org/10.1242/jeb.246299
FASEB J. 2023 Dec;37(12): e23280

A practical perspective on how to develop, implement, execute, and reproduce high-resolution respirometry experiments: The physiologist's guide to an Oroboros O2k.

Maureen A Walsh, Robert V Musci, Robert A Jacobs, Karyn L Hamilton.

  The development of high-resolution respirometry (HRR) has greatly expanded the analytical scope to study mitochondrial respiratory control relative to specific tissue/cell types across various metabolic states. Specifically, the Oroboros Oxygraph 2000 (O2k) is a common tool for measuring rates of mitochondrial respiration and is the focus of this perspective. The O2k platform is amenable for answering numerous bioenergetic questions. However, inherent variability with HRR-derived data, both within and amongst users, can impede progress in bioenergetics research. Therefore, we advocate for several vital considerations when planning and conducting O2k experiments to ultimately enhance transparency and reproducibility across laboratories. In this perspective, we offer guidance for best practices of mitochondrial preparation, protocol selection, and measures to increase reproducibility. The goal of this perspective is to propagate the use of the O2k, enhance reliability and validity for both new and experienced O2k users, and provide a reference for peer reviewers.

Keywords:  Oroboros O2k; bioenergetics; isolated mitochondria; mitochondria; permeabilized fibers; protocol development

DOI:  https://doi.org/10.1096/fj.202301644RR
JACC Heart Fail. 2023 Oct 14. pii: S2213-1779(23)00613-3. [Epub ahead of print]

Managing Obesity in Heart Failure: A Chance to Tip the Scales?

Josephine Harrington, G Michael Felker, Ildiko Lingvay, Neha J Pagidipati, Ambarish Pandey, Darren K McGuire.

  Obesity is associated with incident heart failure (HF), independent of other cardiovascular risk factors. Despite rising rates of both obesity and incident HF, the associations remain poorly understood between: 1) obesity and HF outcomes; and 2) weight loss and HF outcomes. Evidence shows that patients with HF and obesity have high symptom burdens, lower exercise capacity, and higher rates of hospitalization for HF when compared with patients with HF without obesity. However, the impact of weight loss on these outcomes for patients with HF and obesity remains unclear. Recent advances in medical therapies for weight loss have offered a new opportunity for significant and sustained weight loss. Ongoing and recently concluded cardiovascular outcomes trials will offer new insights into the role of weight loss through these therapies in preventing HF and mitigating HF outcomes and symptom burdens among patients with established HF, particularly HF with preserved ejection fraction.

Keywords:  clinical trial; heart failure; obesity; weight loss

DOI:  https://doi.org/10.1016/j.jchf.2023.09.005
J Diabetes Complications. 2023 Oct 21. pii: S1056-8727(23)00230-1. [Epub ahead of print]37(12): 108632

The effect of sodium-glucose cotransporter 2 inhibitors as an adjunct to insulin in patients with type 1 diabetes assessed by continuous glucose monitoring: A systematic review and meta-analysis.

Mengnan Li, Zi'ang Liu, Xifeng Yang, Jiaxin Zhang, Minmin Han, Yi Zhang, Yunfeng Liu.

   AIMS: Patients undergoing insulin-based therapy for type 1 diabetes often experience poor glycemic control characterized by significant fluctuations. This study was undertaken to analyze the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2Is), as an adjunct to insulin, on time in range (TIR) and glycemic variability in patients with type 1 diabetes, using continuous glucose monitoring (CGM). In addition, we examined which type of SGLT2I yielded a superior effect compared to others.
METHODS: We conducted a comprehensive search of PubMed, EMBASE, the Cochrane Library, Web of Science, and clinical trial registry websites, retrieving all eligible randomized clinical trials (RCTs) published up until February 2023. We analyzed the mean TIR, mean amplitude of glucose excursions (MAGE), mean daily glucose (MDG), diabetic ketoacidosis (DKA), standard deviation (SD), total insulin dose, and severe hypoglycemia to evaluate the efficacy and safety of SGLT2Is. A random-effects model was also employed.
RESULTS: This study encompassed 15 RCTs. The meta-analysis revealed that the use of SGLT2Is as an adjuvant therapy to insulin led to a significant increase in TIR (MD = 10.78, 95%CI = 9.33-12.23, I2 = 42 %, P < 0.00001) and a decrease in SD (MD = -0.38, 95%CI = -0.50 to -0.26, I2 = 0 %, P < 0.00001), MAGE (MD = -0.92, 95%CI = -1.17 to -0.67, I2 = 19 %, P < 0.00001), MDG(MD = -1.01, 95%CI = -1.32 to -0.70, I2 = 48 %, P < 0.00001), and total insulin dose (MD = -5.81, 95%CI = -7.81 to -3.82, I2 = 32 %, P < 0.00001). No significant increase was observed in the rate of severe hypoglycemia (RR = 1.04, 95 % CI = 0.76-1.43, P = 0.80). However, SGLT2I therapy was associated with increased DKA occurrence (RR = 2.79, 95 % CI = 1.42-5.48; P = 0.003, I2 = 16 %). In addition, the subgroup analyses based on the type of SGLT2Is revealed that dapagliflozin might exhibit greater efficacy compared to other SGLT2Is across most outcomes.
CONCLUSIONS: SGLT2Is exhibited a positive effect on improving blood glucose level fluctuations. Subgroup analysis showed that dapagliflozin appeared to have more advantages. However, giving due consideration to preventing adverse effects, particularly DKA, is paramount.
REGISTRATION: Prospero CRD42023408276.

Keywords:  Continuous glucose monitoring; Diabetic ketoacidosis; Meta-analysis; Sodium-glucose cotransporter 2 inhibitors; Time in range; Type 1 diabetes

DOI:  https://doi.org/10.1016/j.jdiacomp.2023.108632
Front Physiol. 2023 ;14 1279505

Applied high-intensity interval cardio yoga improves cardiometabolic fitness, energetic contributions, and metabolic flexibility in healthy adults.

So-Young Park, Woo-Hwi Yang.

  Purpose: Currently, there is no interventional approach to increase the intensity of Surya Namaskar a popular hatha yoga sequence used worldwide. Therefore, this study investigated how tempo-based high-intensity interval cardio yoga (HIICY) and traditional interval hatha yoga (TIHY) affects cardiometabolic fitness in active adults. Methods: Twenty physically active male and female individuals were randomly separated into HIICY (5 males, 5 females, 1.5 s tempo) and TIHY (5 males, 5 females, 3 s tempo) groups. The intervention included twelve exercise sessions for 4 weeks in both groups. Participants conducted a ramp test to determine their maximal oxygen uptake (V˙O2max), maximal velocity at V˙O2max (vV˙O2max), and maximal heart rate (HRmax). Afterward, they performed a 10-min high-intensity cardio yoga test (HICYT) to determine heart rate (HRpeak and HRmean), oxygen uptake (V˙O2peak and V˙O2mean), respiratory exchange ratio (RER), blood lactate concentrations (La- peak and ∆La-), fat and carbohydrate oxidations (FATox, CHOox), and energetic contributions (oxidative; W Oxi, glycolytic; W Gly, and phosphagen; W PCr, total energy demand; W Total). Results: V˙O2max and vV˙O2max showed time and group × time interactions (p < 0.01, p < 0.0001, p < 0.001, respectively). V˙O2max after HIICY was significantly higher than in pre-testing and following TIHY (p < 0.001, p < 0.0001, respectively). V˙O2peak, V˙O2mean, RER, HRpeak, and HRmean during the 10-min HICYT showed significant time effects (p < 0.05). ∆La- indicated a group × time interaction (p < 0.05). Group x time interaction effects for FATox at the fourth and sixth minute were observed (p < 0.05, respectively). Absolute (kJ) and relative (%) W Oxi, W Gly, and W Total showed time and group × time interaction effects (p < 0.05, p < 0.01, respectively). Furthermore, %W Gly was reduced following HIICY (p < 0.05). Additionally, V˙O2max and vV˙O2max were highly correlated with W Oxi in kJ (r = 0.91, 0.80, respectively). Moderate to high correlations were observed among CHOox, FATox, and absolute V˙O2max (r = 0.76, 0.62, respectively). Conclusion: A 4-week period of HIICY improved cardiometabolic fitness, oxidative capacity, and metabolic flexibility compared with TIHY, in physically active adults. Therefore, HIICY is suitable as HY-specific HIIT and time-efficient approach for relatively healthy individuals.

Keywords:  V˙O2max; aerobic capacity; lactate; metabolism; physiological adaptation

DOI:  https://doi.org/10.3389/fphys.2023.1279505