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Cited by 291Adipokines, Inflammation, and Metabolic DiseasesRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

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Oxidative Stress and Metabolic Pathologies: From an Adipocentric Point of View

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Le Lay, Soazig, Simard, Gilles, Martinez, Maria Carmen, Andriantsitohaina, Ramaroson·2014·Oxidative Medicine and Cellular Longevity
DOI 10.1155/2014/908539PMC PMC4131099
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Abstract

Oxidative stress plays a pathological role in the development of various diseases including diabetes, atherosclerosis, or cancer. Systemic oxidative stress results from an imbalance between oxidants derivatives production and antioxidants defenses. Reactive oxygen species (ROS) are generally considered to be detrimental for health. However, evidences have been provided that they can act as second messengers in adaptative responses to stress. Obesity represents a major risk factor for deleterious associated pathologies such as type 2 diabetes, liver, and coronary heart diseases. Many evidences regarding obesity-induced oxidative stress accumulated over the past few years based on established correlations of biomarkers or end-products of free-radical-mediated oxidative stress with body mass index. The hypothesis that oxidative stress plays a significant role in the development of metabolic disorders, especially insulin-resistance state, is supported by several studies where treatments reducing ROS production reverse metabolic alterations, notably through improvement of insulin sensitivity, hyperlipidemia, or hepatic steatosis. In this review, we will develop the mechanistic links between oxidative stress generated by adipose tissue in the context of obesity and its impact on metabolic complications development. We will also attempt to discuss potential therapeutic approaches targeting obesity-associated oxidative stress in order to prevent associated-metabolic complications.

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Crossref · 10.1155/2014/908539

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Figures

Figure 1 Different intracellular ROS sources participate in ROS generation by adipocytes. Mitochondria, as the core machinery for energy production through oxidative phosphorylation, is considered as a main source of O2 •−, predominantly produced at complexes I and III. Superoxide anions will be further converted to H2O2 by mitochondrial manganese superoxide dismutase (MnSOD). ROS can also be produced by NADPH oxidases enzymes, in which Nox4 is the main isoform in adipocytes. This isoform presents the particularity to primarily generate H2O2, whereas other NADPH oxidases would generate O2 •− later converted to H2O2 by endogenous SOD. Nitric oxide synthase, whose eNOS and iNOS isoforms are abundantly expressed by adipocytes, might represent another source of ROS since they can be uncoupled to produce O2 •− in the absence of sufficient amounts of substrates.
Figure 1 Different intracellular ROS sources participate in ROS generation by adipocytes. Mitochondria, as the core machinery for energy production through oxidative phosphorylation, is considered as a main source of O2 •−, predominantly produced at complexes I and III. Superoxide anions will be further converted to H2O2 by mitochondrial manganese superoxide dismutase (MnSOD). ROS can also be produced by NADPH oxidases enzymes, in which Nox4 is the main isoform in adipocytes. This isoform presents the particularity to primarily generate H2O2, whereas other NADPH oxidases would generate O2 •− later converted to H2O2 by endogenous SOD. Nitric oxide synthase, whose eNOS and iNOS isoforms are abundantly expressed by adipocytes, might represent another source of ROS since they can be uncoupled to produce O2 •− in the absence of sufficient amounts of substrates.CC BY · PubMed Central
Figure 2 Adaptative or deleterious metabolic responses depending on ROS levels on adipose tissue metabolism. Depending on ROS intracellular levels, adipocytes will trigger different metabolic responses. Physiological levels of ROS, maintained by efficient detoxification system, are able to induce insulin-mimicking effects of H2O2 and to favor adipogenesis, which can be seen as an adaptative response in order to cope with nutrient overloading. In contrast, excessive or inappropriate redox balance will lead to considerable raise in intracellular ROS which will have detrimental effects particularly by altering insulin signaling, adipokine secretion, and adipocyte precursors conversion. Lipid peroxidation, protein carbonylation, and proinflammatory cytokines secretion are increased in obese adipocytes following exposure to high levels of ROS. Moreover, enhancement of ROS production by hypertrophied adipocytes will affect neighboring environment, namely, immune cells infiltrated in WAT or endothelial cells in close vicinity of perivascular adipose tissue. Macrophages are schematically represented as blue (M2 type) or red cells (M1) within adipocytes.
Figure 2 Adaptative or deleterious metabolic responses depending on ROS levels on adipose tissue metabolism. Depending on ROS intracellular levels, adipocytes will trigger different metabolic responses. Physiological levels of ROS, maintained by efficient detoxification system, are able to induce insulin-mimicking effects of H2O2 and to favor adipogenesis, which can be seen as an adaptative response in order to cope with nutrient overloading. In contrast, excessive or inappropriate redox balance will lead to considerable raise in intracellular ROS which will have detrimental effects particularly by altering insulin signaling, adipokine secretion, and adipocyte precursors conversion. Lipid peroxidation, protein carbonylation, and proinflammatory cytokines secretion are increased in obese adipocytes following exposure to high levels of ROS. Moreover, enhancement of ROS production by hypertrophied adipocytes will affect neighboring environment, namely, immune cells infiltrated in WAT or endothelial cells in close vicinity of perivascular adipose tissue. Macrophages are schematically represented as blue (M2 type) or red cells (M1) within adipocytes.CC BY · PubMed Central
Figure 3 Systemic metabolic alterations associated with obesity contribute to the increase in oxidative stress. Hyperglycemia as a hallmark of type II diabetes, a metabolic complication of obesity, induces oxidative stress through activation of the polyol and hexosamine pathways, production of AGE, and increase of DAG synthesis. Excess of circulating lipids induces ROS formation pathways, which contribute to the increase in lipid oxidation and protein carbonylation. Leptin and angiotensin II, secreted at high levels by adipocytes, are inducers of ROS generation and might therefore promote inflammation and lipid peroxidation. Altogether, dysregulation of metabolic parameters occurring with fat mass expansion will contribute to inducing oxidative-stress damages notably at the vascular level.
Figure 3 Systemic metabolic alterations associated with obesity contribute to the increase in oxidative stress. Hyperglycemia as a hallmark of type II diabetes, a metabolic complication of obesity, induces oxidative stress through activation of the polyol and hexosamine pathways, production of AGE, and increase of DAG synthesis. Excess of circulating lipids induces ROS formation pathways, which contribute to the increase in lipid oxidation and protein carbonylation. Leptin and angiotensin II, secreted at high levels by adipocytes, are inducers of ROS generation and might therefore promote inflammation and lipid peroxidation. Altogether, dysregulation of metabolic parameters occurring with fat mass expansion will contribute to inducing oxidative-stress damages notably at the vascular level.CC BY · PubMed Central

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Research works printed but not linked: 11

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Metadata

Authors
Le Lay, S., Simard, G., Martinez, M. C., & Andriantsitohaina, R.
Affiliations
  • INSERM UMR 1063, “Stress Oxydant et Pathologies Métaboliques”, Institut de Biologie en Santé, 4 rue Larrey, 49933 Angers, France
  • Inserm (FR)
Corresponding author
Andriantsitohaina, Ramaroson
ORCID
Venue
Oxidative Medicine and Cellular Longevity
Publisher
Wiley
Published
2014
Volume
2014
Pages
1-18
ISSN
  • 1942-0994 (ISSN-L)
  • 1942-0900
DOI
10.1155/2014/908539
PMC
PMC4131099
OpenAlex
W2139770322
Cited by
291
References
197
Citations by year
2026: 6 · 2025: 13 · 2024: 25 · 2023: 28 · 2022: 25 · 2021: 35 · 2020: 16 · 2019: 29 · 2018: 21 · 2017: 30 · 2016: 33 · 2015: 24 · 2014: 4
FWCI
4.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords
oxidative stress, obesity, adipose tissue, reactive oxygen species, insulin resistance, metabolic disorders, type 2 diabetes, hepatic steatosis, hyperlipidemia, antioxidants, treatment options
MeSH terms
Antioxidants, Humans, Hyperglycemia, Hyperlipidemias, Obesity, Renin-Angiotensin System, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Adipose Tissue, White

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