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Pre-sleep Protein Ingestion Increases Mitochondrial Protein Synthesis Rates During Overnight Recovery from Endurance Exercise: A Randomized Controlled Trial.
Trommelen, J, van Lieshout, GAA, Pabla, P, Nyakayiru, J, Hendriks, FK, Senden, JM, Goessens, JPB, van Kranenburg, JMX, Gijsen, AP, Verdijk, LB, et al
Sports medicine (Auckland, N.Z.). 2023;53(7):1445-1455
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Protein intake prior to overnight sleep has been shown to stimulate muscle protein synthesis overnight and increase muscle mass. This randomised, placebo-controlled, double-blind study of 36 healthy young men compared the effects of pre-sleep casein and whey protein, following a bout of endurance training in the evening. Outcome measures were overnight protein synthesis rates in microfibrils (the contractile organelle of muscle cells) and mitochondria (the energy producing organelle). Ingestion of whey protein resulted in a statistically significantly higher rates of both microfibrillar and mitochondrial protein synthesis compared to placebo. Results for casein were intermediate and not significantly different from either placebo or whey. Both casein and whey protein intake led to a significant increase in circulating total and essential amino acids overnight, compared to placebo, with the whey protein leading to a quicker and casein to a slower but more sustained increase, although the overall increase (area under the curve) did not differ between the two protein groups. There were no differences in sleep, hunger or energy intake at breakfast between groups. The authors conclude that pre-sleep protein intake following endurance exercise increases both microfibrillar and mitochondrial protein synthesis overnight, with casein not being superior to whey.
Abstract
BACKGROUND Casein protein ingestion prior to sleep has been shown to increase myofibrillar protein synthesis rates during overnight sleep. It remains to be assessed whether pre-sleep protein ingestion can also increase mitochondrial protein synthesis rates. Though it has been suggested that casein protein may be preferred as a pre-sleep protein source, no study has compared the impact of pre-sleep whey versus casein ingestion on overnight muscle protein synthesis rates. OBJECTIVE We aimed to assess the impact of casein and whey protein ingestion prior to sleep on mitochondrial and myofibrillar protein synthesis rates during overnight recovery from a bout of endurance-type exercise. METHODS Thirty-six healthy young men performed a single bout of endurance-type exercise in the evening (19:45 h). Thirty minutes prior to sleep (23:30 h), participants ingested 45 g of casein protein, 45 g of whey protein, or a non-caloric placebo. Continuous intravenous L-[ring-13C6]-phenylalanine infusions were applied, with blood and muscle tissue samples being collected to assess overnight mitochondrial and myofibrillar protein synthesis rates. RESULTS Pooled protein ingestion resulted in greater mitochondrial (0.087 ± 0.020 vs 0.067 ± 0.016%·h-1, p = 0.005) and myofibrillar (0.060 ± 0.014 vs 0.047 ± 0.011%·h-1, p = 0.012) protein synthesis rates when compared with placebo. Casein and whey protein ingestion did not differ in their capacity to stimulate mitochondrial (0.082 ± 0.019 vs 0.092 ± 0.020%·h-1, p = 0.690) and myofibrillar (0.056 ± 0.009 vs 0.064 ± 0.018%·h-1, p = 0.440) protein synthesis rates. CONCLUSIONS Protein ingestion prior to sleep increases both mitochondrial and myofibrillar protein synthesis rates during overnight recovery from exercise. The overnight muscle protein synthetic response to whey and casein protein does not differ. CLINICAL TRIAL REGISTRATION NTR7251 .
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Transforming Psoriasis Care: Probiotics and Prebiotics as Novel Therapeutic Approaches.
Buhaș, MC, Candrea, R, Gavrilaș, LI, Miere, D, Tătaru, A, Boca, A, Cătinean, A
International journal of molecular sciences. 2023;24(13)
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Psoriasis is a chronic inflammatory disease of the skin, characterised by dysfunctional proliferation and differentiation of keratinocytes (a type of skin cell). Previous research has shown that psoriasis is associated with gut dysbiosis and increased levels of inflammatory cytokines. The aim of this non-randomised, open-label clinical trial of 63 psoriasis patients was to evaluate the effectiveness of supplementation with a spore-based probiotic (containing 5 strains of Bacillus, taken for 12 weeks) in combination with 3 prebiotics (fructo-oligosaccharides, xylo-oligosaccharides and galacto-oligosaccharides, taken for 8 weeks) alongside standard topical treatment versus topical treatment alone. Outcome measure included Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), inflammatory cytokines, insulin, glucose, lipids, uric acid, body composition, BMI and skin analysis. 15 of the 42 patients in the supplementation group also had a microbiome analysis. Significant improvements were seen in the supplementation group for PASI, DLQI, inflammatory markers, blood lipids, BMI as well as skin analysis, compared to the control group. Favourable changes in microbiome analysis were also observed. It is noteworthy that there were several significant differences between groups at baseline, including severity of psoriasis which was worse in the supplemented group. The authors concluded that patients receiving a combination of a spore-based probiotics and prebiotics alongside standard topical treatment experienced multiple improvements but that further clinical trials are required to establish the most effective combinations and doses.
Abstract
Psoriasis is a chronic inflammatory skin disease with autoimmune pathological characteristics. Recent research has found a link between psoriasis, inflammation, and gut microbiota dysbiosis, and that probiotics and prebiotics provide benefits to patients. This 12-week open-label, single-center clinical trial evaluated the efficacy of probiotics (Bacillus indicus (HU36), Bacillus subtilis (HU58), Bacillus coagulans (SC208), Bacillus licheniformis (SL307), and Bacillus clausii (SC109)) and precision prebiotics (fructooligosaccharides, xylooligosaccharides, and galactooligosaccharides) in patients with psoriasis receiving topical therapy, with an emphasis on potential metabolic, immunological, and gut microbiota changes. In total, 63 patients were evaluated, with the first 42 enrolled patients assigned to the intervention group and the next 21 assigned to the control group (2:1 ratio; non-randomized). There were between-group differences in several patient characteristics at baseline, including age, psoriasis severity (the incidence of severe psoriasis was greater in the intervention group than in the control group), the presence of nail psoriasis, and psoriatic arthritis, though it is not clear whether or how these differences may have affected the study findings. Patients with psoriasis receiving anti-psoriatic local therapy and probiotic and prebiotic supplementation performed better in measures of disease activity, including Psoriasis Area and Severity Index, Dermatology Life Quality Index, inflammatory markers, and skin thickness compared with those not receiving supplementation. Furthermore, in the 15/42 patients in the intervention group who received gut microbiota analysis, the gut microbiota changed favorably following 12 weeks of probiotic and prebiotic supplementation, with a shift towards an anti-inflammatory profile.
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Effect of vaginal probiotics containing Lactobacillus casei rhamnosus (Lcr regenerans) on vaginal dysbiotic microbiota and pregnancy outcome, prospective, randomized study.
Petricevic, L, Rosicky, I, Kiss, H, Janjic, N, Kaufmann, U, Holzer, I, Farr, A
Scientific reports. 2023;13(1):7129
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Preterm delivery (PTD) of babies is thought in some women to be associated with the development of vaginal infections. An imbalance in the bacteria normally present in the vagina and especially a lack of Lactobacillus species can develop into a condition known as bacterial vaginosis (BV), which is a risk factor for PTD. The use of antibiotics is the standard treatment, however concerns on its effectiveness in preventing PTB have been raised. Antibiotics not only eradicate the abnormal bacteria, but also the Lactobacillus. This randomised control trial of 129 women with BV aimed to determine the effect of vaginally applied lactobacilli on the restoration of normal bacteria in the vagina and the rate of PTD. The results showed that women who had a complete lack of Lactobacillus, the vaginal application of Lactobacillus casei rhamnosus, BV was improved and gestational age at delivery and birthweight were both significantly increased, although PTD rate was not. It was concluded that vaginally applied Lactobacillus may be of some benefit to women with BV during pregnancy. This study could be used by healthcare professionals to understand the importance of vaginal microbiota during pregnancy. However, this was a study of very small numbers of women and larger studies are needed before vaginally applied microbiota can be definitively recommended.
Abstract
The intermediate bacterial microbiota is a heterogeneous group that varies in the severity of the dysbiosis, from minor deficiency to total absence of vaginal Lactobacillus spp. We treated women with this vaginal dysbiosis in the first trimester of pregnancy using a vaginally applied lactobacilli preparation to restore the normal microbiota in order to delay the preterm delivery rate. Pregnant women with intermediate microbiota of the vagina and a Nugent score of 4 were enrolled in two groups: intermediate vaginal microbiota and a Nugent score of 4 with lactobacilli (IMLN4) and intermediate vaginal microbiota and a Nugent score of 4 without lactobacilli (IM0N4), with and without vaginal lactobacilli at baseline, respectively. Half of the women in each group received the treatment. Among women without lactobacilli (the IM0N4 group), the Nugent sore decreased by 4 points only in the women who received treatment, and gestational age at delivery and neonatal birthweight were both significantly higher in the treated subgroup than in the untreated subgroup (p = 0.047 and p = 0.016, respectively). This small study found a trend toward a benefit of treatment with vaginal lactobacilli during pregnancy.
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Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.
Deng, N, Reyes-Uribe, L, Fahrmann, JF, Thoman, WS, Munsell, MF, Dennison, JB, Murage, E, Wu, R, Hawk, ET, Thirumurthi, S, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;29(21):4361-4372
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Lynch syndrome (LS) is a genetic disorder conferring a 60% lifetime risk of developing colorectal cancer (CRC). Exercise is associated with a reduction in CRC risk in the general population, potentially mediated via modulation of inflammation. The aim of this non-randomised, controlled trial was to test whether an intervention consisting of 3 x 45-minute cycling classes per week for 12 months affects inflammatory factors (prostaglandin E2, PGE2) in the colorectal mucosa and blood and whether this intervention is feasible in LS carriers. The control group received usual care with one session of exercise counselling. Of 60 patients invited to join the study, 21 (35%) agreed to take part. Of the 11 participants in the intervention group, 9 (81.2%) completed the study with an average adherence to the intervention of 51.3%, compared to 7/10 completing in the control group. VO2 peak (maximal aerobic capacity) increased significantly in the intervention group, compared to the control group over the 12 months. Patients in the intervention group also had a significant reduction in colonic and systemic PGE2 levels compared to controls following intervention. Changes in gene expression which may reflect an increased immune surveillance of the colon were also observed in the intervention group. The authors concluded that the study confirmed that exercise may modulate inflammation in the colonic mucosa in patients at high risk of CRC and that further randomised studies are necessary to confirm the potential benefits of exercise for patients with LS.
Abstract
PURPOSE Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.
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Diverging metabolic effects of 2 energy-restricted diets differing in nutrient quality: a 12-week randomized controlled trial in subjects with abdominal obesity.
Schutte, S, Esser, D, Siebelink, E, Michielsen, CJR, Daanje, M, Matualatupauw, JC, Boshuizen, HC, Mensink, M, Afman, LA
The American journal of clinical nutrition. 2022;116(1):132-150
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Energy restriction (ER) diets are considered an effective strategy for managing obesity and preventing or reducing the risk of associated comorbidities. However, there are very few previous studies comparing the quality of energy restriction diets and their effect on maximising the health benefits. Therefore, this 12-week, parallel-designed, randomised controlled trial compared the effects of a 25% high-quality ER diet with a 25% low-quality ER diet and a habitual diet on cardiometabolic risk factors of 110 participants with abdominal obesity. Both ER diets were nutritionally balanced. The high-quality ER diet had added Monounsaturated fatty acids (MUFAs), Omega-3 Polyunsaturated fatty acids (n-3 PUFAs), fibre, and plant protein and had less fructose in it. The low-quality ER diet contained Saturated fatty acids (SFAs) and monosaccharides such as fructose. At the end of the 12-week trial, participants on the 25% high-quality diet showed more promising results in weight loss, reduction in cholesterol and triglycerides, and adipose tissue gene expression of energy metabolism pathways compared to the 25% low-quality ER diet. Insulin-sensitive participants with abdominal obesity on a 25% high-quality diet lost more weight compared to the rest of the participants. Further robust studies are required to evaluate the findings due to the limitations of this study. However, healthcare professionals can use the results of this study to understand the beneficial effects of an ER diet when it is enriched with specific nutrients.
Abstract
BACKGROUND Despite the established relation between energy restriction (ER) and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still a subject of debate. OBJECTIVES The aim of the study was to examine the additional effects of nutrient quality on top of ER. METHODS A parallel-designed, 12-week 25% ER dietary intervention study was conducted (clinicaltrials.gov: NCT02194504). Participants aged 40-70 years with abdominal obesity were randomized over 3 groups: a 25% ER high-nutrient-quality diet (n = 40); a 25% ER low-nutrient-quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, and the high-nutrient-quality ER diet was enriched in MUFAs, n-3 PUFAs, fiber, and plant protein and reduced in fructose. Before and after the intervention, intrahepatic lipids, body fat distribution, fasting and postprandial responses to a mixed-meal shake challenge test of cardiometabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. RESULTS The high-nutrient-quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low-nutrient-quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an antiatherogenic lipoprotein profile, and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low-quality ER diet. Explorative analyses showed that the difference in weight loss between the two ER diets was specifically present in insulin-sensitive subjects (HOMA-IR ≤ 2.5), in whom the high-nutrient-quality diet induced 3.9 kg more weight loss than the low-nutrient-quality diet. CONCLUSIONS A high-nutrient-quality 25% ER diet is more beneficial for cardiometabolic health than a low-nutrient-quality 25% ER diet. Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue.
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Sleep Disturbance Affects Immune Factors in Clinical Liver Cancer Patients.
Wang, Z, Wang, Y, Huang, J, Xu, J, Chen, F, Zhu, Z, Gao, L, Qin, J, Liu, B, Liang, C
Current oncology (Toronto, Ont.). 2022;29(10):7943-7952
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Many studies have shown that sleep disorders promote tumor growth and can impair immunity at the cellular level. There is however a lack of research in patients with liver cancer. The aim of this study was the asses the quality of sleep and the prevalence of disturbed sleep in patients with liver cancer and to explore whether sleep quality influences immune factors. 210 patients with liver cancer were randomly divided into 2 groups: HBV (Hepatitis B virus) cirrhosis and non-HBV cirrhosis. Their sleep quality was evaluated using a questionnaire and then the patients were divided into 2 groups according to these scores. The association between sleep disturbances and immune factors was analysed by logistic regression models. Over half the patient experienced poor sleep quality. Sleep disturbances were higher in patients with liver cancer of non-HBV cirrhosis than with that coming from the HBV virus. A rise in CD3+ T cells and a reduction in NK cells are associated with sleep disturbances in patients with non-HBV cirrhosis liver cancer. Medicines that can promote sleep and therefore improve immune function might be beneficial. Non-pharmacological sleep interventions to improve sleep quality, should be a safer choice where there are complex drug side effects.
Abstract
BACKGROUND Sleep-wake disturbance is prevalent in patients with liver cancer, but there is no direct evidence of its association and related biological mechanisms. Our study was to assess quality of sleep and to describe prevalence of sleep disturbances in patients with different etiologies of liver cancer, especially to explore whether sleep quality influences immune factors. METHODS A total of 210 patients with liver cancer from August 2015 to December 2015 were randomly divided into two groups including HBV cirrhosis and non-HBV cirrhosis. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate their sleep quality, and then 202 patients enrolled in this study were divided into two groups according to their PSQI scores: PSQI ≤ 5 and PSQI > 5. The association between sleep disturbances and immune factors was analyzed by logistic regression models. RESULTS A total of 56.9% of liver cancer patients experienced poor sleep quality (PSQI > 5). The prevalence of sleep disturbances was significantly higher in patients with liver cancer of non-hepatitis B virus (HBV) cirrhosis than with that evolving from HBV cirrhosis (66.7% vs. 50%, p = 0.018). In non-HBV cirrhosis liver cancer patients, the PSQI > 5 group had a higher percentage of CD3+ T cells (71.06 ± 11.07 vs. 63.96 ± 14.18, p = 0.014) and lower natural killer (NK) cells (14.67 ± 9.65 vs. 20.5 ± 10.77, p = 0.014) compared with patients with PSQI ≤ 5. Logistic regression further confirmed that liver cancer patients without HBV cirrhosis are more prone to experience poor sleep with increased CD3+ T cells (OR = 1.07, 95% CI = 1.01-1.13, p = 0.030) and decreased NK cells (OR = 0.92, 95% CI = 0.85-0.98, p = 0.014). Our results indicate that increased CD3+ T cells and decreased NK cells are both associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis. CONCLUSIONS Most liver cancer patients suffer from sleep disturbances, especially evolving from non-HBV cirrhosis. A rise in CD3+ T cells and a reduction in NK cells are associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis.
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Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.
Aghapour, M, Tulen, CBM, Abdi Sarabi, M, Weinert, S, Müsken, M, Relja, B, van Schooten, FJ, Jeron, A, Braun-Dullaeus, R, Remels, AH, et al
Cells. 2022;11(11)
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Cigarette smoking can affect airway epithelial cells, causing overproduction of mucus, damage, and inflammation, which may result in the progression of airway diseases. Airway epithelial cells (AEC) rely on mitochondria for energy, and mitochondrial dysfunction may affect innate immunity and the integrity of the airway epithelium. Cigarette smoking is found to accelerate mitochondrial damage within AEC. Maintaining a normal microbial composition within the respiratory tract is essential for maintaining immunity. There is evidence that smoking cigarettes disrupts the microbial composition and increases the spread of pathogenic bacteria such as Streptococcus pneumoniae (Sp) which causes inflammation. By exposing 16HBE cells to Sp and cigarette smoke extract (CSE), this study investigated the effect of cigarette smoking on mitochondrial dysfunction in ACE in an in vitro model. Additionally, the study examined the direct and indirect pathways involved in cigarette smoking-induced mitochondrial dysfunction and altered innate immune response to Sp infection. CSE exposure decreases mitochondrial complex protein levels and mitochondrial membrane potential, which affects energy production. It also increases mitochondrial oxidative stress and mitochondrial degradation. All these factors lead to mitochondrial dysfunction in ACE. CSE exposure to ACE was associated with altered gene expression in the tight and adherence junctions that serve as a protective barrier against pathogens and pollutants and reduced type I interferon immune responses to Sp. Using the results of this study, healthcare professionals can gain a better understanding of the impact of cigarette smoking on mitochondrial dysfunction and how it increases susceptibility to Sp-related immune responses. It is necessary to conduct further studies to evaluate the effects of cigarette smoking on mitochondrial dysfunction, microbial composition disruption, and the interaction between AECs and elevated immune responses.
Abstract
Mitochondrial functionality is crucial for the execution of physiologic functions of metabolically active cells in the respiratory tract including airway epithelial cells (AECs). Cigarette smoke is known to impair mitochondrial function in AECs. However, the potential contribution of mitochondrial dysfunction in AECs to airway infection and airway epithelial barrier dysfunction is unknown. In this study, we used an in vitro model based on AECs exposed to cigarette smoke extract (CSE) followed by an infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress as an indicator of mitochondrial stress were quantified upon CSE and Sp treatment. In addition, expression of proteins associated with mitophagy, mitochondrial content, and biogenesis as well as mitochondrial fission and fusion was quantified. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with indices of mitochondrial function. We observed that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp.
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Morphological Adaptation in the Jejunal Mucosa after Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers: Data from a Randomized Crossover Study.
Casselbrant, A, Wallenius, V, Elebring, E, Marschall, HU, Johansson, BR, Helander, HF, Fändriks, L
Nutrients. 2022;14(19)
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The small intestinal mucosa is a large organ which acts as an intestinal barrier. The jejunal mucosa is the largest part of the small intestinal mucosa, and its functions include digestion and absorption of food. Epithelium cells on the surface of the small intestine renew every few days. Therefore, this single-centre, randomised, unblinded, crossover study looked at how jejunal mucosal cells change after two weeks of an isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) in fifteen healthy people. The study also measured ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) and mitochondria following the isocaloric HFD and HCD. Neither HFD nor HCD changes the mucosal surface enlargement factor. However, at the ultrastructural level, there was a significant surface enlargement in the bases of the villi after following HCD than HFD. In addition, HFD increased the number of mitochondrial cristae in the erythrocytes than HCD. The increased number of mitochondrial cristae in the erythrocytes was associated with the increased expression of HMGCS2. Healthcare professionals can use the results of this study to understand how short-term implementation of different diets affects jejunal mucosal morphology at the ultrastructural level. Further robust studies are required to evaluate the long-term effects of HFD and HCD in jejunal mucosa and how the morphological adaptations impact people with obesity.
Abstract
BACKGROUND AND AIMS The conditions for jejunal glucose absorption in healthy subjects have not been thoroughly studied. In this study we investigated differences in the jejunal villi enlargement factor, as well as ultrastructural aspects of the surface enterocytes and mitochondria, comparing 2 weeks of high-carbohydrate (HCD) versus high-fat diets (HFD). We also measured the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) in relation to jejunal mitochondria. METHODS A single-centre, randomized, unblinded crossover study in 15 healthy volunteers ingesting strictly controlled equicaloric diets (either HCD or HFD), with 60% energy from the respective source. An enteroscopy was carried out after 2 weeks of each diet and jejunal mucosal biopsies were acquired. Conventional histology, immunofluorescent staining, transmission electron microscopy and confocal microscopy were used. RESULTS The villi did not demonstrate any change in the epithelial enlargement factor. Despite an increased mitosis, there were no changes in apoptotic indices. However, the ultrastructural analysis demonstrated a significant increase in the enlargement factor at the bases of the villi. The mitochondria demonstrated increased amounts of cristae after the HFD. The confocal microscopy revealed increased HMGCS2 per mitochondrial marker at the top of the villi after the HFD compared to the HCD. CONCLUSION There is a morphometric adaption in the jejunal mucosa following the 2-week diets, not only on a histological level, but rather on the ultrastructural level. This study supports the notion that mitochondrial HMGCS2 is regulated by the fat content of the diet and is involved in the expression of monosaccharide transporters.
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A high-carbohydrate diet lowers the rate of adipose tissue mitochondrial respiration.
Bikman, BT, Shimy, KJ, Apovian, CM, Yu, S, Saito, ER, Walton, CM, Ebbeling, CB, Ludwig, DS
European journal of clinical nutrition. 2022;76(9):1339-1342
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The hormone insulin plays a fundamental role in cellular nutrient signalling, including mitochondrial function. The aim of this study was to test the hypothesis that a high-carbohydrate diet would lower measures of mitochondrial respiration in adipose tissue, consistent with the carbohydrate-insulin model of obesity. This study is an ancillary study of the Framingham State Food Study, in which the primary outcome was total energy expenditure. Data of twenty-seven participants were included in this report. Results show that a high-carbohydrate diet lowers mitochondrial respiratory function. Authors conclude the study’s sample may not reflect mitochondrial activity in all body fat depots. Thus, further research is required in order to replicate the study’s findings, conduct quantitative energetic studies, examine generalizability to other populations and experimental conditions, and explore translation to the prevention and treatment of obesity.
Abstract
Adipocyte mitochondrial respiration may influence metabolic fuel partitioning into oxidation versus storage, with implications for whole-body energy expenditure. Although insulin has been shown to influence mitochondrial respiration, the effects of dietary macronutrient composition have not been well characterized. The aim of this exploratory study was to test the hypothesis that a high-carbohydrate diet lowers the oxygen flux of adipocyte mitochondria ex vivo. Among participants in a randomized-controlled weight-loss maintenance feeding trial, those consuming a high-carbohydrate diet (60% carbohydrate as a proportion of total energy, n = 10) had lower rates of maximal adipose tissue mitochondrial respiration than those consuming a moderate-carbohydrate diet (40%, n = 8, p = 0.039) or a low-carbohydrate diet (20%, n = 9, p = 0.005) after 10 to 15 weeks. This preliminary finding may provide a mechanism for postulated calorie-independent effects of dietary composition on energy expenditure and fat deposition, potentially through the actions of insulin on fuel partitioning.
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Molecular Regulators of Muscle Mass and Mitochondrial Remodeling Are Not Influenced by Testosterone Administration in Young Women.
Horwath, O, Moberg, M, Hirschberg, AL, Ekblom, B, Apró, W
Frontiers in endocrinology. 2022;13:874748
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Testosterone is a sex hormone normally found in higher amounts in adult males than females. Testosterone plays a number of important roles, including influencing muscle size and strength. Treatment with testosterone has been shown to increase lean mass and muscle strength in women as well as men. However, female-only studies are limited, and the precise mechanisms underlying these changes are not well understood. This randomised control trial examined the effect of testosterone administration on regulators of muscle protein turnover and mitochondrial function in muscle samples collected from young women. 48 healthy, pre-menopausal women were assigned to receive either 10mg of transdermal testosterone gel per day, or a placebo, for 10 weeks. Muscle samples were collected via biopsy before and after the intervention. Testosterone administration did not appear to have a significant effect on androgen receptors, 5-alpha reductase, anabolic signalling, or mitochondrial remodelling in muscle tissue. The researchers concluded that improvements in muscle size and oxidative capacity following testosterone administration cannot be explained by changes in protein expression related to muscle protein turnover or mitochondrial remodelling. The authors went on to suggest that the small sample size in this study may have reduced the ability to detect small but biologically relevant changes in protein levels. Within the research, there is large variability among studies in terms of sex, age, route of administration and length of treatment, which makes putting these findings into context of the wider literature difficult.
Abstract
Testosterone (T) administration has previously been shown to improve muscle size and oxidative capacity. However, the molecular mechanisms underlying these adaptations in human skeletal muscle remain to be determined. Here, we examined the effect of moderate-dose T administration on molecular regulators of muscle protein turnover and mitochondrial remodeling in muscle samples collected from young women. Forty-eight healthy, physically active, young women (28 ± 4 years) were assigned in a random double-blind fashion to receive either T (10 mg/day) or placebo for 10-weeks. Muscle biopsies collected before and after the intervention period were divided into sub-cellular fractions and total protein levels of molecular regulators of muscle protein turnover and mitochondrial remodeling were analyzed using Western blotting. T administration had no effect on androgen receptor or 5α-reductase levels, nor on proteins involved in the mTORC1-signaling pathway (mTOR, S6K1, eEF2 and RPS6). Neither did it affect the abundance of proteins associated with proteasomal protein degradation (MAFbx, MuRF-1 and UBR5) and autophagy-lysosomal degradation (AMPK, ULK1 and p62). T administration also had no effect on proteins in the mitochondria enriched fraction regulating mitophagy (Beclin, BNIP3, LC3B-I, LC3B-II and LC3B-II/I ratio) and morphology (Mitofilin), and it did not alter the expression of mitochondrial fission- (FIS1 and DRP1) or fusion factors (OPA1 and MFN2). In summary, these data indicate that improvements in muscle size and oxidative capacity in young women in response to moderate-dose T administration cannot be explained by alterations in total expression of molecular factors known to regulate muscle protein turnover or mitochondrial remodeling.