β-carotene oxygenase 2 deficiency-triggered mitochondrial oxidative stress promotes low-grade inflammation and metabolic dysfunction

Wu, Lei; Lu, Peiran; Guo, Xin; Song, Kun; Lyu, Yi; Bothwell, James; Wu, Jinglong; Hawkins, Olivia; Clarke, Stephen; Lucas, Edralin A.; Smith, Brenda J.; Chowanadisai, Winyoo; Hartson, Steve; Ritchey, Jerry W.; Wang, Weiqun; Medeiros, Denis M.; Li, Shitao; Lin, Dingbo

doi:10.1016/j.freeradbiomed.2021.01.003

Cited by 19 publications

(32 citation statements)

References 70 publications

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“…Notably, treatment with Mitotempo, a mitochondria-specific antioxidant agent derivative of MitoQ, was shown to be effective in alleviating mitochondrial oxidative stress in various tissues of the Bco2 −/− mice. 34 Our treatment of the mutant mice with NAC, a potent antioxidant and ROS scavenger 63 albeit not mitochondria-specific, confirmed that indeed this was the case. After two weeks of treatment, NAC restored retinoic acid levels as well as Pdk4 mRNA and protein expression in the heart of the Bco2 −/− mice (Figure 5F,G) without affecting retinoic acid levels in the mutant liver (Figure S5), and without perturbing retinoic acid levels and Pdk4 status in the heart of the WT control group (Figure 5E,F).…”

Section: Discussionsupporting

confidence: 61%

Retinoic acid regulates pyruvate dehydrogenase kinase 4 (Pdk4) to modulate fuel utilization in the adult heart: Insights from wild‐type and β‐carotene 9′,10′ oxygenase knockout mice

et al. 2022

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Regulation of the pyruvate dehydrogenase (PDH) complex by the pyruvate dehydrogenase kinase PDK4 enables the heart to respond to fluctuations in energy demands and substrate availability. Retinoic acid, the transcriptionally active form of vitamin A, is known to be involved in the regulation of cardiac function and growth during embryogenesis as well as under pathological conditions. Whether retinoic

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Section: Discussionsupporting

confidence: 61%

Retinoic acid regulates pyruvate dehydrogenase kinase 4 (Pdk4) to modulate fuel utilization in the adult heart: Insights from wild‐type and β‐carotene 9′,10′ oxygenase knockout mice

et al. 2022

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“…OS may represent a connection between the two since it has been demonstrated that OS can alter OC/u-OC ratio [166], and u-OC exerts protective effects in diabetes counteracting OS thus increasing insulin sensitivity [167]. It is still speculative that mutations in mitochondrial antioxidants enzyme can influence this equilibrium in the bone as demonstrated in some experimental models [168].…”

Section: Other Implications Due To Oxidative Stressmentioning

confidence: 99%

Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

Mancini

Bruno

Vergani

et al. 2021

IJMS

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The pathophysiology of Polycystic Ovary Syndrome (PCOS) is quite complex and different mechanisms could contribute to hyperandrogenism and anovulation, which are the main features of the syndrome. Obesity and insulin-resistance are claimed as the principal factors contributing to the clinical presentation; in normal weight PCOS either, increased visceral adipose tissue has been described. However, their role is still debated, as debated are the biochemical markers linked to obesity per se. Oxidative stress (OS) and low-grade inflammation (LGI) have recently been a matter of researcher attention; they can influence each other in a reciprocal vicious cycle. In this review, we summarize the main mechanism of radical generation and the link with LGI. Furthermore, we discuss papers in favor or against the role of obesity as the first pathogenetic factor, and show how OS itself, on the contrary, can induce obesity and insulin resistance; in particular, the role of GH-IGF-1 axis is highlighted. Finally, the possible consequences on vitamin D synthesis and activation on the immune system are briefly discussed. This review intends to underline the key role of oxidative stress and low-grade inflammation in the physiopathology of PCOS, they can cause or worsen obesity, insulin-resistance, vitamin D deficiency, and immune dyscrasia, suggesting an inverse interaction to what is usually considered.

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“…It has been reported that mice with whole-body knockout of BCDO2 function developed metabolic dysfunction derived from the peripheral and hypothalamus, even when fed a diet thought to be free of carotenoids. Importantly, failure of gene expression related to the antioxidant response, such as Nrf2, was observed frequently in the knockout mice used in these studies [ 104 , 105 , 106 ]. In conclusion, although the level of influence of AX on this pathway is not known, it is suggested that carotenoids may activate Nrf-2 in a different way to the commonly known Nrf2/Keap1 pathway ( Figure 3 .).…”

Section: Mechanism By Which Astaxanthin Enhances Mitochondrial Energy Metabolismmentioning

confidence: 99%

“…In relation to AX, the effect of BCDO2-generated AX metabolites should be considered in the future, because it has only been studied in toxicological aspects, such as CYP induction in rats [ 125 ]. Perhaps independently of these features, BCDO2 itself probably functions as an anti-inflammatory factor through the modulation of several signaling pathways and gene expression [ 103 , 104 , 105 , 106 , 236 , 237 ].…”

Section: Mechanism By Which Astaxanthin Enhances Mitochondrial Energy Metabolismmentioning

confidence: 99%

Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants

Nishida

Nawaz

Hecht³

et al. 2021

Nutrients

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Astaxanthin is a member of the carotenoid family that is found abundantly in marine organisms, and has been gaining attention in recent years due to its varied biological/physiological activities. It has been reported that astaxanthin functions both as a pigment, and as an antioxidant with superior free radical quenching capacity. We recently reported that astaxanthin modulated mitochondrial functions by a novel mechanism independent of its antioxidant function. In this paper, we review astaxanthin’s well-known antioxidant activity, and expand on astaxanthin’s lesser-known molecular targets, and its role in mitochondrial energy metabolism.

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β-carotene oxygenase 2 deficiency-triggered mitochondrial oxidative stress promotes low-grade inflammation and metabolic dysfunction

Cited by 19 publications

References 70 publications

Retinoic acid regulates pyruvate dehydrogenase kinase 4 (Pdk4) to modulate fuel utilization in the adult heart: Insights from wild‐type and β‐carotene 9′,10′ oxygenase knockout mice

Retinoic acid regulates pyruvate dehydrogenase kinase 4 (Pdk4) to modulate fuel utilization in the adult heart: Insights from wild‐type and β‐carotene 9′,10′ oxygenase knockout mice

Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights

Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants

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