Prevailing vitamin D status influences mitochondrial and glycolytic bioenergetics in peripheral blood mononuclear cells obtained from adults

Calton, Emily K.; Keane, Kevin N.; Soares, Mário J.; Rowlands, Jordan; Newsholme, Philip

doi:10.1016/j.redox.2016.10.007

Cited by 35 publications

(31 citation statements)

References 64 publications

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“…Abnormal PBMC bioenergetics have previously been investigated in other chronic diseases including obesity [ 32 ], type 2 diabetes mellitus (T2DM) [ 33 ], and rheumatoid arthritis[ 34 ]. Hartman et al .…”

Section: Introductionmentioning

confidence: 99%

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome

et al. 2017

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Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency. While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand.

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Section: Introductionmentioning

confidence: 99%

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome

et al. 2017

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“…This is an important finding as alterations in paternal chromatin can have dramatic consequences on reproduction especially if the oocyte is unable to repair such paternal nuclear damage. Given the extensive antioxidant and regulatory roles of vitamin D on gene expression, 60‐67 further studies are needed to determine which processes (either in the testis during spermatogenesis or in the epididymis during post‐testicular maturation) could be affected.…”

Section: Discussionmentioning

confidence: 99%

Impact of vitamin D deficiency on mouse sperm structure and function

et al. 2020

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Background In rodents and humans, vitamin D deficiency (VDD) is associated with altered sperm structure and function (primarily decreased motility and morphological abnormalities) that are primarily attributed to VDD‐induced hypocalcemia. However, it is suspected that VDD has much more drastic effects on mammalian spermatozoa. Objectives The purpose of this study was to illustrate that VDD, depending on its severity and duration, can alter sperm nuclear integrity and can also lead to the loss of spermatozoa's ability to support embryonic development. Materials and methods A mouse model of induced VDD combining the action of a vitamin D‐deficient diet, UV exposure limitation, and paricalcitol injections; a vitamin D2 analog that catabolizes endogenous vitamin D by increasing the expression of CYP24A, a member of the cytochrome P450 family, has been used to create different grades of VDD. Results We show that the most significant sperm defect recorded concerns the integrity of the paternal nucleus, which is both decondensed and fragmented in moderate‐to‐severe VDD situations. Consistent with the known consequences of fertilization with DNA‐damaged spermatozoa, we show that paternal VDD decreases the ability of spermatozoa to optimally support fertilization and embryonic development. Discussion and Conclusion Given the worldwide high prevalence of VDD in humans, and although obtained in an animal model, the data presented here suggest that subfertile/infertile males may benefit from VDD testing and that attempts to correct serum vitamin D levels could be considered prior to conception, either naturally or through ART.

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“…We are aware of only one study that has examined whether the bioenergetic profile of peripheral blood mononuclear cells (PBMCs) was related to differences in inflammatory status; those data support an association of changes in interleukin-6 and bioenergetic profile [14]. Recently, we demonstrated that 25(OH)D below 50 nmol/L was associated with increased oxidative and glycolytic bioenergetic profile responses in PBMCs obtained from adults [15]. Whether change in 25(OH)D was associated with altered bioenergetic profiles remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells

et al. 2017

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BackgroundVitamin D status [25(OH)D] has recently been reported to be associated with altered cellular bioenergetic profiles of peripheral blood mononuclear cells (PBMCs). No study has tracked the seasonal variation of 25(OH)D and its putative influence on whole body energy metabolism, cellular bioenergetic profiles, inflammatory markers and clinical chemistry.Material and methodsWhole body energy metabolism and substrate utilisation were measured by indirect calorimetry. PBMCs obtained from the same subjects were isolated from whole blood, counted and freshly seeded. Bioenergetic analysis (mitochondrial stress test and glycolysis stress test) was performed using the Seahorse XFe96 flux analyser. 25(OH)D was assessed using the Architect immunoassay method.Results25(OH)D increased by a median (IQR) of 14.40 (20.13) nmol/L (p<0.001) from winter to summer and was accompanied by significant improvements in indices of insulin sensitivity, McAuley's index (p=0.019) and quantitative insulin sensitivity check index (p=0.028). PBMC mitochondrial parameters basal respiration, non-mitochondrial respiration, ATP production, proton leak, and maximal respiration decreased in summer compared to winter. Similarly, PBMC glycolytic parameters glycolytic activity, glucose response, and glycolytic capacity were all reduced in summer compared to winter. There was also a trend for absolute resting metabolic rate (RMR) to decrease (p=0.066). Markers of systemic inflammation MCP-1, IL-6, IL-8, IL-10, and IL-12p70 decreased significantly in summer compared to winter. Participants who entered winter with a low 25(OH)D (<50 nmol/L), had the greatest alteration in bioenergetic parameters in summer, relative to those with winter 25(OH)D concentrations of 50–75 nmol/L or >75 nmol/L. The absolute change in 25(OH)D was not associated with altered bioenergetics.ConclusionSeasonal improvements in 25(OH)D was associated with reduced systemic inflammation, PBMC bioenergetic profiles and whole body energy metabolism. These observational changes in PBMC bioenergetics were most pronounced in those who had insufficient 25(OH)D in winter. The data warrants confirmation through cause and effect study designs.

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Prevailing vitamin D status influences mitochondrial and glycolytic bioenergetics in peripheral blood mononuclear cells obtained from adults

Cited by 35 publications

References 64 publications

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome

Impact of vitamin D deficiency on mouse sperm structure and function

Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells

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