bims-mifefi Biomed News
on Mitochondria and female physiology
Issue of 2024‒05‒19
two papers selected by
Kayla Vandiver, East Carolina University



  1. Front Clin Diabetes Healthc. 2024 ;5 1346716
      Background: People with type 2 diabetes (T2D) have lower rates of physical activity (PA) than the general population. This is significant because insufficient PA is linked to cardiovascular morbidity and mortality, particularly in individuals with T2D. Previously, we identified a novel barrier to physical activity: greater perceived effort during exercise in women. Specifically, women with T2D experienced exercise at low-intensity as greater effort than women without T2D at the same low-intensity - based on self-report and objective lactate measurements. A gap in the literature is whether T2D confers greater exercise effort in both sexes and across a range of work rates.Objectives: Our overarching objective was to address these gaps regarding the influence of T2D and relative work intensity on exercise effort. We hypothesized that T2D status would confer greater effort during exercise across a range of work rates below the aerobic threshold.
    Methods: This cross-sectional study enrolled males and post-menopausal females aged 50-75 years. Measures of exercise effort included: 1) heart rate, 2) lactate and 3) self-report of Rating of Perceived Exertion (RPE); each assessment was during the final minute of a 5-minute bout of treadmill exercise. Treadmill exercise was performed at 3 work rates: 1.5 mph, 2.0 mph, and 2.5 mph, respectively. To determine factors influencing effort, separate linear mixed effect models assessed the influence of T2D on each outcome of exercise effort, controlling for work rate intensity relative to peak oxygen consumption (%VO2peak). Models were adjusted for any significant demographic associations between effort and age (years), sex (male/female), baseline physical activity, or average blood glucose levels.
    Results: We enrolled n=19 people with T2D (47.4% female) and n=18 people (55.6% female) with no T2D. In the models adjusted for %VO2peak, T2D status was significantly associated with higher heart rate (p = 0.02) and lactate (p = 0.01), without a significant association with RPE (p = 0.58).
    Discussions: Across a range of low-to-moderate intensity work rates in older, sedentary males and females, a diagnosis of T2D conferred higher objective markers of effort but did not affect RPE. Greater objective effort cannot be fully attributed to impaired fitness, as it persisted despite adjustment for %VO2peak. In order to promote regular exercise and reduce cardiovascular risk for people with T2D, 1) further efforts to understand the mechanistic targets that influence physiologic exercise effort should be sought, and 2) comparison of the effort and tolerability of alternative exercise training prescriptions is warranted.
    Keywords:  cardiorespiratory fitness (MeSH term); exercise; heart rate; lactate; physical exertion (MeSH term); type 2 diabetes mellitus
    DOI:  https://doi.org/10.3389/fcdhc.2024.1346716
  2. Free Radic Biol Med. 2024 May 11. pii: S0891-5849(24)00457-X. [Epub ahead of print]220 312-323
      Podocytes are crucial for regulating glomerular permeability. They have foot processes that are integral to the renal filtration barrier. Understanding their energy metabolism could shed light on the pathogenesis of filtration barrier injury. Lactate has been increasingly recognized as more than a waste product and has emerged as a significant metabolic fuel and reserve. The recent identification of lactate transporters in podocytes, the expression of which is modulated by glucose levels and lactate, highlights lactate's relevance. The present study investigated the impact of lactate on podocyte respiratory efficiency and mitochondrial dynamics. We confirmed lactate oxidation in podocytes, suggesting its role in cellular energy production. Under conditions of glucose deprivation or lactate supplementation, a significant shift was seen toward oxidative phosphorylation, reflected by an increase in the oxygen consumption rate/extracellular acidification rate ratio. Notably, lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB) isoforms, which are involved in lactate conversion to pyruvate, were detected in podocytes for the first time. The presence of lactate led to higher intracellular pyruvate levels, greater LDH activity, and higher LDHB expression. Furthermore, lactate exposure increased mitochondrial DNA-to-nuclear DNA ratios and resulted in upregulation of the mitochondrial biogenesis markers peroxisome proliferator-activated receptor coactivator-1α and transcription factor A mitochondrial, regardless of glucose availability. Changes in mitochondrial size and shape were observed in lactate-exposed podocytes. These findings suggest that lactate is a pivotal energy source for podocytes, especially during energy fluctuations. Understanding lactate's role in podocyte metabolism could offer insights into renal function and pathologies that involve podocyte injury.
    Keywords:  LDHA; LDHB; Lactate dehydrogenase; Mitochondrial biogenesis; Oxidative phosphorylation
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.05.022