Young Men With Poor Cardiorespiratory Fitness Combined With lower Testosterone Have High Levels of Oxidized LDL Lipids—Being Fit Alters This Relationship

Kosola, Jussi; Ahotupa, Markku; Kyröläinen, Heikki; Santtila, Matti; Vasankari, Tommi

doi:10.1123/ijsnem.23.6.629

Cited by 2 publications

(3 citation statements)

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“…Protein concentrations were analyzed using the BCA Protein Assay Kit (Thermo Fisher Scientific, Inc.), and 30 μg protein was loaded in each lane for gel electrophoresis. The procedure were performed as previously described 21 . The primary antibodies used were as follows: anti-COX-2 (1:1000), anti-CD36 (1:1000), anti-phospho-p38 (1:1000), anti-p38 (1:2000), anti-phospho-JNK (1:2000), anti-JNK (1:2000), anti-phospho-ERK1/2 (1:2000), anti-ERK1/2 (1:1000), anti-STAR (1:1000), anti-p450scc (1:1000), anti-3β-HSD (1:2000), anti-17β-HSD (1:200), anti-Ndufs1 (1:2000), anti-SdhB (1:10,000), anti-Uqcrfs1 (1:4000), anti-Fech (1:1000), anti-CytC (1:1000), and GAPDH (1:2000).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Circulating oxidized low-density lipoprotein (oxLDL), the oxidative modified form of LDL, is associated with obesity, metabolic syndrome, and cardiovascular disease in adults [17][18][19] . Testosterone deficiency together with higher concentrations of oxLDL has been reported in epidemiological studies; however, there is currently no evidence for a causal relationship 20,21 . Oxidative damage and inflammatory factors induced by significantly high levels of oxLDL are involved in the dysfunction and apoptosis of vascular endothelial cells 22,23 .…”

Section: Introductionmentioning

confidence: 98%

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Oxidized-LDL inhibits testosterone biosynthesis by affecting mitochondrial function and the p38 MAPK/COX-2 signaling pathway in Leydig cells

et al. 2020

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Abnormal lipid/lipoprotein metabolism induced by obesity may affect spermatogenesis by inhibiting testosterone synthesis in Leydig cells. It is crucial to determine which components of lipoproteins inhibit testosterone synthesis. Circulating oxidized low-density lipoprotein (oxLDL), the oxidized form of LDL, has been reported to be an independent risk factor for decreased serum testosterone levels. However, whether oxLDL has a damaging effect on Leydig cell function and the detailed mechanisms have been rarely studied. This study first showed the specific localization of oxLDL and mitochondrial structural damage in testicular Leydig cells of high-fat diet-fed mice in vivo. We also found that oxLDL reduced the mitochondrial membrane potential (MMP) by disrupting electron transport chain and inhibited testosterone synthesis-related proteins and enzymes (StAR, P450scc, and 3β-HSD), which ultimately led to mitochondrial dysfunction and decreased testosterone synthesis in Leydig cells. Further experiments demonstrated that oxLDL promoted lipid uptake and mitochondrial dysfunction by inducing CD36 transcription. Meanwhile, oxLDL facilitated COX2 expression through the p38 MAPK signaling pathway in Leydig cells. Blockade of COX-2 attenuated the oxLDL-induced decrease in StAR and P450scc. Our clinical results clarified that the increased serum oxLDL level was associated with a decline in circulating testosterone levels. Our findings amplify the damaging effects of oxLDL and provide the first evidence that oxLDL is a novel metabolic biomarker of male-acquired hypogonadism caused by abnormal lipid metabolism.

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Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Oxidized-LDL inhibits testosterone biosynthesis by affecting mitochondrial function and the p38 MAPK/COX-2 signaling pathway in Leydig cells

et al. 2020

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“…The humoral response to oxidized LDL and atherosclerosis progression has been poorly investigated in athletes or high endurance-trained individuals [8]. The endurance training through metabolic and immunological adaptation could impact vascular and atherosclerosis modulation [9,10].…”

Section: Introductionmentioning

confidence: 99%

Immunometabolic and Vascular Health Responses among High Endurance Trained Subjects

Fonseca,

Bittencourt,

Monteiro

et al. 2023

Int J Sports Med

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We aimed to examine the impact of high endurance training on vascular health parameters and immune-endocrine responses against modified low-density lipoprotein (LDL) particles. This observational, cross-sectional study included high endurance-trained and healthy non-trained subjects. Vascular ultrasound was used to assess vascular health parameters based on carotid intima-media thickness and endothelial function (flow-mediated dilation). Enzyme-linked immunosorbent assays were used to measure interleukin (IL)-8 and IL-10, autoantibody isotypes anti-oxidized LDL (oxLDL) and anti-apolipoprotein B (ApoB-D) peptide. Plasma levels of the corticosterone and 17 α-hydroxyprogesterone hormones were analyzed by mass spectrometry. This study enrolled 96 subjects, of whom 44 were high endurance-trained and 52 were healthy non-trained individuals. Smaller carotid intima-media thickness values were observed in the high-endurance trained than in the healthy non-trained males, while no differences were observed between female groups. Flow-mediated dilation measurements did not differ by training or sex. The humoral immune responses to IgG anti-oxLDL and IgM anti-ApoB-D autoantibodies showed an isotype imbalance between the high-endurance trained and the non-trained groups. Immunoendocrine parameters showed inverse correlations between 17 α-hydroxyprogesterone concentrations and carotid intima-media thickness measurements. Direct correlations were found between IL-10 concentrations and flow-mediated dilation measurements. Chronic high-endurance exercise modulates immune-endocrine and vascular health parameters, in a sex-dependent manner.

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Young Men With Poor Cardiorespiratory Fitness Combined With lower Testosterone Have High Levels of Oxidized LDL Lipids—Being Fit Alters This Relationship

Cited by 2 publications

References 0 publications

Oxidized-LDL inhibits testosterone biosynthesis by affecting mitochondrial function and the p38 MAPK/COX-2 signaling pathway in Leydig cells

Oxidized-LDL inhibits testosterone biosynthesis by affecting mitochondrial function and the p38 MAPK/COX-2 signaling pathway in Leydig cells

Immunometabolic and Vascular Health Responses among High Endurance Trained Subjects

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