Oxidative stress and lipid peroxidation by-products at the crossroad between adipose organ dysregulation and obesity-linked insulin resistance

Murdolo, Giuseppe; Piroddi, Marta; Luchetti, Francesca; Tortoioli, Cristina; Canonico, Barbara; Zerbinati, Chiara; Galli, Francesco; Iuliano, Luigi

doi:10.1016/j.biochi.2012.12.014

Cited by 104 publications

(83 citation statements)

References 128 publications

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“…Another risk factor for adipocyte hypertrophy is aging, via the development of mitochondrial dysfunction, which in turn is implicated in excessive lipid storage (Kirkland et al, 1994;Karagiannides et al, 2001;Kirkland et al, 2002). Hypertrophy-induced inflammation might have a basis for oxidative stress establishment (Murdolo et al, 2013). High ROS levels led to a decrease in adiponectin expression and secretion (Wang et al, 2013a,b), an important protein for insulin sensitivity and exhibiting anti-atherogenic and anti-inflammatory effects.…”

Section: Consequences Of Ros Imbalance For White Adipose Tissuementioning

confidence: 99%

“…Another study has shown that preadipocyte proliferation was inhibited by mitochondrial ROS, which therefore affect the size of the white adipocyte pool (Carriere et al, 2003). Subcutaneous abdominal fat samples from diabetic compared to obese and non-diabetic control subjects displayed increased levels of lipid peroxidation products such as 4-HNE, linking oxidative stress to insulin resistance (Murdolo et al, 2013 Figure 3: Oxidative stress is originated in overcaloric conditions increasing the risk for several metabolic dysfunction outcomes. Physiological ROS levels are mandatory for a proper adipogenesis contributing to adipose tissue and overall organism homeostasis.…”

Section: Consequences Of Ros Imbalance For White Adipose Tissuementioning

confidence: 99%

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The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction

Castro

Grune

Speckmann

2016

Biological Chemistry

125

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White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho)physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e.g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.

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Section: Consequences Of Ros Imbalance For White Adipose Tissuementioning

confidence: 99%

Section: Consequences Of Ros Imbalance For White Adipose Tissuementioning

confidence: 99%

The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction

Castro

Grune

Speckmann

2016

Biological Chemistry

125

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“…Adipose tissue is vital for energy homeostasis and serves as an essential endocrine and immune organ (25). Adipose tissue is the main site for lipid peroxidation and acts as a major "sink" to store and handle free radicalinduced peroxidation products (36). Oxidative DNA lesions produced by lipid peroxidation products block DNA replicative polymerases and stall the progression of DNA replication (13,14), which triggers cell cycle arrest and leads to different cellular responses, depending on the magnitude of DNA damage.…”

Section: Impact Of Pol η On Cellular Senescence and Adipogenesis Usingmentioning

confidence: 99%

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

Chen

Harris

Hatahet

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Obesity and the metabolic syndrome have evolved to be major health issues throughout the world. Whether loss of genome integrity contributes to this epidemic is an open question. DNA polymerase η (pol η), encoded by the xeroderma pigmentosum (XP-V) gene, plays an essential role in preventing cutaneous cancer caused by UV radiation-induced DNA damage. Herein, we demonstrate that pol η deficiency in mice (pol η −/− ) causes obesity with visceral fat accumulation, hepatic steatosis, hyperleptinemia, hyperinsulinemia, and glucose intolerance. In comparison to WT mice, adipose tissue from pol η −/− mice exhibits increased DNA damage and a greater DNA damage response, indicated by upregulation and/or phosphorylation of ataxia telangiectasia mutated (ATM), phosphorylated H 2 AX (γH 2 AX), and poly[ADP-ribose] polymerase 1 (PARP-1). Concomitantly, increased cellular senescence in the adipose tissue from pol η −/− mice was observed and measured by up-regulation of senescence markers, including p53, p16 Ink4a , p21, senescence-associated (SA) β-gal activity, and SA secretion of proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) as early as 4 wk of age. Treatment of pol η −/− mice with a p53 inhibitor, pifithrin-α, reduced adipocyte senescence and attenuated the metabolic abnormalities. Furthermore, elevation of adipocyte DNA damage with a high-fat diet or sodium arsenite exacerbated adipocyte senescence and metabolic abnormalities in pol η −/− mice. In contrast, reduction of adipose DNA damage with N-acetylcysteine or metformin ameliorated cellular senescence and metabolic abnormalities. These studies indicate that elevated DNA damage is a root cause of adipocyte senescence, which plays a determining role in the development of obesity and insulin resistance.T he human genome is constantly challenged by exogenous and endogenous DNA damaging agents. To ensure genome integrity, human cells have faithful DNA replication machinery and DNA repair systems that are coordinated by DNA damage response networks. In response to different extents or types of DNA lesions, the DNA damage response activates appropriate cellular responses, including transient or permanent (senescence) cell cycle arrest, or apoptosis, to minimize the detrimental effects of DNA lesions (1). Reduction or deficiency in DNA repair/replication enzyme activity is well documented to increase vulnerability for the development of cancer, neurodegenerative diseases, and aging (2). In addition, defective DNA repair enzymes are associated with the metabolic symptom; for example, DNA glycosylase (Neil1)-and OGG1-deficient mice are obese (3-5), and nucleotide excision repair protein ERCC1-XPF deficiency causes lipodystrophy (6). Furthermore, DNA damage response protein ataxia telangiectasia mutated (ATM) suppresses JNK activity through p53 signaling and mediates an antioxidant action that has been suggested to be relevant to the metabolic syndrome (7). Nucleotide excision repair XP-A protein may affect metabolism by altering mitochondrial...

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“…In cultured adipocytes, elevated FFA resulted in increased oxidative stress, via NADPH oxidase activation, and oxidative stress led to a dysregulated secretion of adipokines, as shown by Furokawa et al, What's more, in the same study, increased ROS production accompanied by augmented expression of NADPH oxidase and decreased expression of antioxidative enzymes was observed in the adipose tissue of obese mice (83). Therefore, the nutrition-induced oxidative stress could possibly lead to an adverse local redox status that could interfere in the role of free radicals in adipose tissue (84).…”

Section: Adipose Tissuementioning

confidence: 58%

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women

Diamanti-Kandarakis

Papalou²,

Kandaraki

et al. 2017

European Journal of Endocrinology

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Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders.

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Oxidative stress and lipid peroxidation by-products at the crossroad between adipose organ dysregulation and obesity-linked insulin resistance

Cited by 104 publications

References 128 publications

The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction

The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women

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