MPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity

Katsouda, Antonia; Valakos, Dimitrios; Dionellis, Vasilis S.; Bibli, Sofia Iris; Akoumianakis, Ioannis; Karaliota, Sevasti; Zuhra, Karim; Fleming, Ingrid; Nagahara, Noriyuki; Havaki, Sophia; Gorgoulis, Vassilis G.; Thanos, Dimitris; Antoniades, Charalambos; Szabó, Csaba; Papapetropoulos, Andreas

doi:10.1084/jem.20211894

Cited by 23 publications

(17 citation statements)

References 88 publications

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“…CSE has been previously reported to play a key role in the regulation of the adipogenesis, although with opposite effects as compared with 3-MST. Indeed, while CSE inhibition reduced lipid storage [ 10 , 27 ], 3-MST inhibition increased lipid accumulation as shown both in vivo model [ 28 ] and in vitro (Fig. 2D , E ).…”

Section: Resultsmentioning

confidence: 83%

“…6A ). Importantly, in a recently published study, increased adipocyte surface area was also demonstrated in vivo after 3-MST inhibition or silencing in C57Bl/6 J mice [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

“…A recently published study has also explored some of the molecular mechanisms related to the regulation of lipogenesis by 3-MST using a murine high-fat-diet model [ 28 ]. This study concluded that 3-MST ablation leads to increase of ROS levels with consequent stimulation of a cascade of events triggered by HIF1α activation.…”

Section: Discussionmentioning

confidence: 99%

“…The same study also demonstrated that HIF1α, in turn, downregulates the expression levels of translocase of inner/outer mitochondrial membrane (in TIM/TOM complex), thus impairing mitochondrial protein import. This effect has various functional consequences, including suppression of Krebs cycle, oxidative phosphorylation, and fatty acid oxidation, eventually leading to excessive lipid accumulation, increased iWAT mass, impaired glucose/insulin tolerance, and increased body weight [ 28 ]. In the current paper as well as in the in vivo study discussed in the current paragraph [ 28 ], H 2 S administration—by means of either the slow releaser GYY4137 (current study) or the donor compound SG1002 [ 28 ]—reversed the chain of events leading to lipid accumulation both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…This effect has various functional consequences, including suppression of Krebs cycle, oxidative phosphorylation, and fatty acid oxidation, eventually leading to excessive lipid accumulation, increased iWAT mass, impaired glucose/insulin tolerance, and increased body weight [ 28 ]. In the current paper as well as in the in vivo study discussed in the current paragraph [ 28 ], H 2 S administration—by means of either the slow releaser GYY4137 (current study) or the donor compound SG1002 [ 28 ]—reversed the chain of events leading to lipid accumulation both in vitro and in vivo. Indeed, several lines of independent, emerging data [ 16 , 18 , 19 ] suggest that the 3-MST/H 2 S system serves as a counterregulatory system to tonically inhibit adipocyte development, and, consequently, obesity (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of the 3-mercaptopyruvate sulfurtransferase—hydrogen sulfide system promotes cellular lipid accumulation

et al. 2022

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H2S is generated in the adipose tissue by cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase (3-MST). H2S plays multiple roles in the regulation of various metabolic processes, including insulin resistance. H2S biosynthesis also occurs in adipocytes. Aging is known to be associated with a decline in H2S. Therefore, the question arises whether endogenous H2S deficiency may affect the process of adipocyte maturation and lipid accumulation. Among the three H2S-generating enzymes, the role of 3-MST is the least understood in adipocytes. Here we tested the effect of the 3-MST inhibitor 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE) and the H2S donor (GYY4137) on the differentiation and adipogenesis of the adipocyte-like cells 3T3-L1 in vitro. 3T3-L1 cells were differentiated into mature adipocytes in the presence of GYY4137 or HMPSNE. HMPSNE significantly enhanced lipid accumulation into the maturing adipocytes. On the other hand, suppressed lipid accumulation was observed in cells treated with the H2S donor. 3-MST inhibition increased, while H2S donation suppressed the expression of various H2S-producing enzymes during adipocyte differentiation. 3-MST knockdown also facilitated adipocytic differentiation and lipid uptake. The underlying mechanisms may involve impairment of oxidative phosphorylation and fatty acid oxidation as well as the activation of various differentiation-associated transcription factors. Thus, the 3-MST/H2S system plays a tonic role in suppressing lipid accumulation and limiting the differentiation of adipocytes. Stimulation of 3-MST activity or supplementation of H2S—which has been recently linked to various experimental therapeutic approaches during aging—may be a potential experimental approach to counteract adipogenesis.

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Section: Resultsmentioning

confidence: 83%

“…6A ). Importantly, in a recently published study, increased adipocyte surface area was also demonstrated in vivo after 3-MST inhibition or silencing in C57Bl/6 J mice [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Inhibition of the 3-mercaptopyruvate sulfurtransferase—hydrogen sulfide system promotes cellular lipid accumulation

et al. 2022

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Mitochondrial Function and Dysfunction in White Adipocytes and Therapeutic Implications

Wang,

Huynh,

2024

Comprehensive Physiology

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For a long time, white adipocytes were thought to function as lipid storages due to the sizeable unilocular lipid droplet that occupies most of their space. However, recent discoveries have highlighted the critical role of white adipocytes in maintaining energy homeostasis and contributing to obesity and related metabolic diseases. These physiological and pathological functions depend heavily on the mitochondria that reside in white adipocytes. This article aims to provide an up‐to‐date overview of the recent research on the function and dysfunction of white adipocyte mitochondria. After briefly summarizing the fundamental aspects of mitochondrial biology, the article describes the protective role of functional mitochondria in white adipocyte and white adipose tissue health and various roles of dysfunctional mitochondria in unhealthy white adipocytes and obesity. Finally, the article emphasizes the importance of enhancing mitochondrial quantity and quality as a therapeutic avenue to correct mitochondrial dysfunction, promote white adipocyte browning, and ultimately improve obesity and its associated metabolic diseases. © 2024 American Physiological Society. Compr Physiol 14:5581‐5640, 2024.

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Anti‐obesity effects of Beta vulgaris and Eruca sativa‐based extracts

Markou,

Katsouda,

Papaioannou

et al. 2024

Phytotherapy Research

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Obesity is a major source of morbidity worldwide with more than 2 billion adults being overweight or obese. The incidence of obesity has tripled in the last 50 years, leading to an increased risk for a variety of noncommunicable diseases. Previous studies have demonstrated the positive effects of green leafy vegetables on weight gain and obesity and have attributed these beneficial properties, at least in part, to nitrates and isothiocyanates. Nitrates are converted to nitric oxide (NO) and isothiocyanates are known to release hydrogen sulfide (H2S). Herein, we investigated the effect of extracts and fractions produced from Beta vulgaris and Eruca sativa for their ability to limit lipid accumulation, regulate glucose homeostasis, and reduce body weight. Extracts from the different vegetables were screened for their ability to limit lipid accumulation in adipocytes and hepatocytes and for their ability to promote glucose uptake in skeletal muscle cultures; the most effective extracts were next tested in vivo. Wild type mice were placed on high‐fat diet for 8 weeks to promote weight gain; animals receiving the selected B. vulgaris and E. sativa extracts exhibited attenuated body weight. Treatment with extracts also led to reduced white adipose tissue depot mass, attenuated adipocyte size, reduced expression of Dgat2 and PPARγ expression, and improved liver steatosis. In contrast, the extracts failed to improve glucose tolerance in obese animals and did not affect blood pressure. Taken together, our data indicate that extracts produced from B. vulgaris and E. sativa exhibit anti‐obesity effects, suggesting that dietary supplements containing nitrates and sulfide‐releasing compounds might be useful in limiting weight gain.

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MPST sulfurtransferase maintains mitochondrial protein import and cellular bioenergetics to attenuate obesity

Cited by 23 publications

References 88 publications

Inhibition of the 3-mercaptopyruvate sulfurtransferase—hydrogen sulfide system promotes cellular lipid accumulation

Inhibition of the 3-mercaptopyruvate sulfurtransferase—hydrogen sulfide system promotes cellular lipid accumulation

Mitochondrial Function and Dysfunction in White Adipocytes and Therapeutic Implications

Anti‐obesity effects of Beta vulgaris and Eruca sativa‐based extracts

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