bims-mifefi Biomed News
on Mitochondria and female physiology
Issue of 2024–04–21
ten papers selected by
Kayla Vandiver, East Carolina University
  1. Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients.
  2. Delineating the contribution of ageing and physical activity to changes in mitochondrial characteristics across the lifespan.
  3. Skeletal muscle mitochondria: A potential target for postmenopausal hormone replacement therapy.
  4. Are there sex differences in the variability of fasting metabolism?
  5. Niacin supplementation attenuates the regression of three-dimensional capillary architecture in unloaded female rat skeletal muscle.
  6. Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes.
  7. Extracellular Vesicles in Metabolic and Vascular Insulin Resistance.
  8. Age-Dependent Changes in the Production of Mitochondrial Reactive Oxygen Species in Human Skeletal Muscle.
  9. The paradox of fatty-acid β-oxidation in muscle insulin resistance: Metabolic control and muscle heterogeneity.
  10. The relationship between resting metabolic rate and quality of life is moderated by age and body composition in women: a cross-sectional study.
  1. Gynecol Endocrinol. 2024 Dec;40(1): 2341701
    Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients.
    Alessandro D Genazzani, Christian Battipaglia, Laura Rusce, Greta Prampolini, Claudia Aio, Francesco Ricciardiello, Martina Foschi, Alessandra Sponzilli, Elisa Semprini, Tabatha Petrillo.
       OBJECTIVE: To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients.
    METHODS: This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated.
    RESULTS: ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease.
    CONCLUSION: ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.
    Keywords:  C-peptide; NAFLD; PCOS; alpha lipoic acid; familial diabetes; insulin resistance
    DOI:  https://doi.org/10.1080/09513590.2024.2341701
  2. Mol Aspects Med. 2024 Apr 15. pii: S0098-2997(24)00031-1. [Epub ahead of print]97 101272
    Delineating the contribution of ageing and physical activity to changes in mitochondrial characteristics across the lifespan.
    Matthew J-C Lee, Nicholas J Saner, Alessandra Ferri, Esther García-Domínguez, James R Broatch, David J Bishop.
      Ageing is associated with widespread physiological changes prominent within all tissues, including skeletal muscle and the brain, which lead to a decline in physical function. To tackle the growing health and economic burdens associated with an ageing population, the concept of healthy ageing has become a major research priority. Changes in skeletal muscle mitochondrial characteristics have been suggested to make an important contribution to the reductions in skeletal muscle function with age, and age-related changes in mitochondrial content, respiratory function, morphology, and mitochondrial DNA have previously been reported. However, not all studies report changes in mitochondrial characteristics with ageing, and there is increasing evidence to suggest that physical activity (or inactivity) throughout life is a confounding factor when interpreting age-associated changes. Given that physical activity is a potent stimulus for inducing beneficial adaptations to mitochondrial characteristics, delineating the influence of physical activity on the changes in skeletal muscle that occur with age is complicated. This review aims to summarise our current understanding and knowledge gaps regarding age-related changes to mitochondrial characteristics within skeletal muscle, as well as to provide some novel insights into brain mitochondria, and to propose avenues of future research and targeted interventions. Furthermore, where possible, we incorporate discussions of the modifying effects of physical activity, exercise, and training status, to purported age-related changes in mitochondrial characteristics.
    DOI:  https://doi.org/10.1016/j.mam.2024.101272
  3. Acta Physiol (Oxf). 2024 Apr 17. e14149
    Skeletal muscle mitochondria: A potential target for postmenopausal hormone replacement therapy.
    Takashi Yokota.
      
    DOI:  https://doi.org/10.1111/apha.14149
  4. J Appl Physiol (1985). 2024 Apr 18.
    Are there sex differences in the variability of fasting metabolism?
    Louise Bradshaw, Jariya Buniam, James A Betts, Javier T Gonzalez.
      There is evidence across species and across many traits that males display greater between-individual variance. In contrast, (premenopausal) females display large within-individual variance in sex hormone concentrations, which can increase within-individual variance in many other parameters. The latter may contribute to the lower representation of females in metabolic research. This study is a pooled secondary analysis of data from 7 crossover studies to investigate the between-individual and the within-individual variance in fasting plasma metabolites, resting metabolic rate (RMR) and body mass. Females demonstrated higher within-individual variability of plasma 17β-estradiol (CV 15±15 % for males vs 38±34 % for females, p<0.001) and progesterone concentrations (CV 13±11 % for males vs 52±51 % for females, p<0.001) but there were no meaningful differences in the variability of plasma glucose (CV 4±3 % for males vs 5 ± 5 % for females), insulin, lactate, triglycerides (CV 15±9 % for males vs 15 ± 10 % for females), and non-esterified fatty acid concentrations, nor in RMR and body mass (CV 0.43±0.34 % for males vs for 0.42±0.33 % females; p>0.05 for all outcomes). Males displayed higher between-individual variance in RMR compared to females (SD 224 kcal×day-1 for males vs 151 kcal×day-1 for females). In conclusion, these data do not provide evidence that females show greater within-individual variability in many fasting metabolic variables, RMR or body mass compared to males. We conclude that including females in metabolic research is unlikely to introduce greater within-individual variance when using the recruitment and control procedures described in these studies.
    Keywords:  Sexual dimorphism; metabolism; variability
    DOI:  https://doi.org/10.1152/japplphysiol.00053.2024
  5. Physiol Rep. 2024 Apr;12(8): e16019
    Niacin supplementation attenuates the regression of three-dimensional capillary architecture in unloaded female rat skeletal muscle.
    Hao Lin, Jihao Xing, Han Pan, Takumi Hirabayashi, Noriaki Maeshige, Ryosuke Nakanishi, Hiroyo Kondo, Hidemi Fujino.
      Inactivity can lead to muscle atrophy and capillary regression in skeletal muscle. Niacin (NA), known for inducing hypermetabolism, may help prevent this capillary regression. In this study involving adult female Sprague-Dawley rats, the animals were randomly assigned to one of four groups: control (CON), hindlimb unloading (HU), NA, and HU with NA supplementation (HU + NA). For a period of 2 weeks, the rats in the HU and HU + NA groups underwent HU, while those in the NA and HU + NA groups received NA (750 mg/kg) twice daily through oral administration. The results demonstrated that HU lowered capillary number, luminal diameter, and capillary volume, as well as decreased succinate dehydrogenase activity, slow fiber composition, and PGC-1α expression within the soleus muscle. However, NA supplementation prevented these alterations in capillary structure due to unloading by stimulating PGC-1α factors and inhibiting mitochondrial dysfunction. Therefore, NA supplementation could serve as a potential therapeutic approach for preserving the capillary network and mitochondrial metabolism of muscle fibers during periods of inactivity.
    Keywords:  capillary regression; mitochondrial metabolism; muscle atrophy; niacin
    DOI:  https://doi.org/10.14814/phy2.16019
  6. Nat Med. 2024 Apr 16.
    Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes.
    Marie-France Hivert, Frédérique White, Catherine Allard, Kaitlyn James, Sana Majid, François Aguet, Kristin G Ardlie, Jose C Florez, Andrea G Edlow, Luigi Bouchard, Pierre-Étienne Jacques, S Ananth Karumanchi, Camille E Powe.
      Reduced insulin sensitivity (insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM). We conducted transcriptomic profiling of 434 human placentas and identified a positive association between insulin-like growth factor binding protein 1 gene (IGFBP1) expression in the placenta and insulin sensitivity at ~26 weeks gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which, together with high gene expression levels in our placenta samples, suggests a placental or decidual source. Higher circulating IGFBP1 levels were associated with greater insulin sensitivity (lesser insulin resistance) at ~26 weeks gestation in the same cohort and in two additional pregnancy cohorts. In addition, low circulating IGFBP1 levels in early pregnancy predicted subsequent GDM diagnosis in two cohorts of pregnant women. These results implicate IGFBP1 in the glycemic physiology of pregnancy and suggest a role for placental IGFBP1 deficiency in GDM pathogenesis.
    DOI:  https://doi.org/10.1038/s41591-024-02936-5
  7. J Vasc Res. 2024 Apr 12. 1-13
    Extracellular Vesicles in Metabolic and Vascular Insulin Resistance.
    Steven K Malin, Uta Erdbrügger.
       BACKGROUND: Insulin resistance is a major etiological factor in obesity, type 2 diabetes, and cardiovascular disease (CVD). Endothelial dysfunction may precede impairments in insulin-stimulated glucose uptake, thereby making it a key feature in development of CVD. However, the mechanism by which vascular tissue becomes dysfunctional is not clear.
    SUMMARY: Extracellular vesicles (EVs) have emerged as potential mediators of insulin resistance and vascular dysfunction. EVs are membrane-bound particles released by tissues following cellular stress or activation. They carry "cargo" (e.g., insulin signaling proteins, eNOS-nitric oxide, and miRNA) that are believed to promote inter-cellular and interorgan communications. Herein, we review the underlying physiology of EVs in relation to type 2 diabetes and CVD risk. Specifically, we discuss how EVs may modulate metabolic (e.g., skeletal muscle, liver, and adipose) insulin sensitivity, and propose that EVs may modulate vascular insulin action to influence both endothelial function and arterial stiffness. We lastly identify how EVs may play a unique role following exercise to promote metabolic and vascular insulin sensitivity changes.
    KEY MESSAGE: Gaining insight toward insulin-mediated EV mechanism has potential to identify novel pathways regulating cardiometabolic health and provide foundation for examining EVs as unique biomarkers and targets to prevent and/or treat chronic diseases.
    Keywords:  Arterial stiffness; Endothelial dysfunction; Glycemic control; Hypertension; Physical activity
    DOI:  https://doi.org/10.1159/000538197
  8. Biochemistry (Mosc). 2024 Feb;89(2): 299-312
    Age-Dependent Changes in the Production of Mitochondrial Reactive Oxygen Species in Human Skeletal Muscle.
    Mikhail Yu Vyssokikh, Maksim A Vigovskiy, Vladislav V Philippov, Yakov R Boroday, Mariya V Marey, Olga A Grigorieva, Tatiana F Vepkhvadze, Nadezhda S Kurochkina, Ludmila A Manukhova, Anastasiya Yu Efimenko, Daniil V Popov, Vladimir P Skulachev.
      A decrease in muscle mass and its functionality (strength, endurance, and insulin sensitivity) is one of the integral signs of aging. One of the triggers of aging is an increase in the production of mitochondrial reactive oxygen species. Our study was the first to examine age-dependent changes in the production of mitochondrial reactive oxygen species related to a decrease in the proportion of mitochondria-associated hexokinase-2 in human skeletal muscle. For this purpose, a biopsy was taken from m. vastus lateralis in 10 young healthy volunteers and 70 patients (26-85 years old) with long-term primary arthrosis of the knee/hip joint. It turned out that aging (comparing different groups of patients), in contrast to inactivity/chronic inflammation (comparing young healthy people and young patients), causes a pronounced increase in peroxide production by isolated mitochondria. This correlated with the age-dependent distribution of hexokinase-2 between mitochondrial and cytosolic fractions, a decrease in the rate of coupled respiration of isolated mitochondria and respiration when stimulated with glucose (a hexokinase substrate). It is discussed that these changes may be caused by an age-dependent decrease in the content of cardiolipin, a potential regulator of the mitochondrial microcompartment containing hexokinase. The results obtained contribute to a deeper understanding of age-related pathogenetic processes in skeletal muscles and open prospects for the search for pharmacological/physiological approaches to the correction of these pathologies.
    Keywords:  aging; hexokinase; mitochondria; mitochondrial reactive oxygen species; skeletal muscle
    DOI:  https://doi.org/10.1134/S0006297924020093
  9. Biochim Biophys Acta Mol Basis Dis. 2024 Apr 15. pii: S0925-4439(24)00161-3. [Epub ahead of print] 167172
    The paradox of fatty-acid β-oxidation in muscle insulin resistance: Metabolic control and muscle heterogeneity.
    Marcel A Vieira-Lara, Barbara M Bakker.
      The skeletal muscle is a metabolically heterogeneous tissue that plays a key role in maintaining whole-body glucose homeostasis. It is well known that muscle insulin resistance (IR) precedes the development of type 2 diabetes. There is a consensus that the accumulation of specific lipid species in the tissue can drive IR. However, the role of the mitochondrial fatty-acid β-oxidation in IR and, consequently, in the control of glucose uptake remains paradoxical: interventions that either inhibit or activate fatty-acid β-oxidation have been shown to prevent IR. We here discuss the current theories and evidence for the interplay between β-oxidation and glucose uptake in IR. To address the underlying intricacies, we (1) dive into the control of glucose uptake fluxes into muscle tissues using the framework of Metabolic Control Analysis, and (2) disentangle concepts of flux and catalytic capacities taking into account skeletal muscle heterogeneity. Finally, we speculate about hitherto unexplored mechanisms that could bring contrasting evidence together. Elucidating how β-oxidation is connected to muscle IR and the underlying role of muscle heterogeneity enhances disease understanding and paves the way for new treatments for type 2 diabetes.
    Keywords:  Diabetes; Fatty-acid β-oxidation; Glucose metabolism; Insulin resistance; Mitochondria
    DOI:  https://doi.org/10.1016/j.bbadis.2024.167172
  10. BMC Womens Health. 2024 Apr 13. 24(1): 235
    The relationship between resting metabolic rate and quality of life is moderated by age and body composition in women: a cross-sectional study.
    Melissa J Benton, Andrea M Hutchins.
       BACKGROUND: Health-related quality of life (HRQOL) is related to body composition, which is also related to resting metabolic rate (RMR). RMR can be increased by exercise and diet interventions that are not dependent on changes in body composition, so a link between RMR and HRQOL may provide interventions that directly improve HRQOL in women.
    METHODS: One hundred twenty women (median age 63.5 [IQR: 53.0-71.0] years) completed one-time measurement of body composition (multi-frequency bioelectrical impedance), RMR (handheld calorimetry), and HRQOL (RAND-36). Physical (PCS) and mental (MCS) composite scores were calculated for the RAND-36. Pearson correlations were used to identify relationships between RMR, body composition, and HRQOL. Variables at the p < .01 level were entered into multiple regression models.
    RESULTS: Median body mass index was 26.1 [IQR: 23.2-30.9] kg/m2 and median lean mass index was 16.1 [IQR: 14.6-17.3] kg/m2. Body composition consisted of fat mass (median 27.2 [IQR: 20.3-34.7] kg) and lean mass (median 42.7 [IQR: 38.2-46.9] kg). Median RMR was 1165.0 [IQR: 1022.5-1380.0] kcal/day. Median HRQOL scores were PCS (84.0 [IQR: 74.0-93.0]) and MCS (85.0 [IQR: 74.3-90.0]). RMR was not directly related to PCS, but was directly and negatively related to MCS (p = .002). RMR was significantly and positively related to body composition (lean mass: p < .001; fat mass: p < .001), body mass index (p = .005), and lean mass index (p < .001); but only fat mass (PCS: p < .001; MCS: p < .001) and body mass index (PCS: p < .001; MCS: p < .001) were related to HRQOL, although the relationship was negative. In addition, age was found to be significantly negatively related to RMR (p < .001) and PCS (p = .003). Regression models confirmed the moderating influence of age and body composition on the relationship between RMR and HRQOL. RMR, age, fat mass, and body mass index explained 24% (p < .001) of variance in PCS; and RMR, fat mass, and body mass index explained 15% (p < .001) of variance in MCS.
    CONCLUSION: In women, the relationship between RMR and HRQOL is moderated by age and body composition. Understanding these pathways will allow clinicians and researchers to direct interventions more effectively.
    Keywords:  Body composition; Health-related quality of life; Mental composite score; Physical composite score; RAND-36; Resting metabolic rate
    DOI:  https://doi.org/10.1186/s12905-024-03085-0
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