Catalase post-translational modifications as key targets in the control of erythrocyte redox homeostasis in children with obesity and insulin resistance

González-Domínguez, Álvaro; Visiedo, Francisco; Domínguez-Riscart, Jesús; Durán-Ruiz, Ma Carmen; Sáez-Benito, Ana; Lechuga-Sancho, Alfonso María; Mateos, Rosa M.

doi:10.1016/j.freeradbiomed.2022.08.017

Cited by 12 publications

(6 citation statements)

References 37 publications

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“…Childhood obesity and MS are pathophysiologycally related with in ammation and OS, which are in turn highly interrelated and potentiate each other. Indeed, children with MS exhibit depleted or ineffective cellular antioxidant defenses, together with a pro-oxidative metal homeostasis [28][29][30][31] . MS is known to be a risk factor for T2DM and cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Altered Insulin Secretion Dynamics Relates to Oxidative Stress and Inflammasome Activation in Children with Obesity and Insulin Resistance

González-Domínguez,

Belmonte,

Domínguez-Riscart

et al. 2023

Preprint

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Background Insulin resistance (IR) is considered the main driver of obesity related metabolic complications, and is related with oxidative stress and inflammation which in turn promote each other. However, there is still no specific definition of IR in children. Altered insulin secretion dynamics are also related with worse metabolic profiles and type 2 diabetes mellitus development, thus we aimed to test whether if insulin response relates with oxidative stress and inflammation.Methods We conducted a case-control study, including 132 children (33 controls; 42 with obesity but no IR; 25 with obesity and IR and an early insulin response to OGTT; 32 with obesity, IR, and a late insulin peak), and studied variables related with lipid and carbohydrate metabolism, oxidative stress, inflammation and inflammasome activationResults Children with obesity and IR with an early insulin response, behaved much like those without IR an almost every parameter. It was late responders who presented an impaired antioxidant system and elevated oxidative damage in erythrocytes and plasma, and inflammasome activation at their white blood cells, despite lower classical inflammation markers. Increased uric acid levels seems to be one of the underlying mechanisms for inflammasome activation.Conclusions It is insulin response to an OGTT what better identifies children with obesity suffering oxidative stress and inflammasome activation. Uric acid could be mediating this pathological inflammatory response by activating NLRP3 in peripheral blood mononuclear cells.

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Section: Discussionmentioning

confidence: 99%

Altered Insulin Secretion Dynamics Relates to Oxidative Stress and Inflammasome Activation in Children with Obesity and Insulin Resistance

González-Domínguez,

Belmonte,

Domínguez-Riscart

et al. 2023

Preprint

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“…Anthropometric data were measured and evaluated by endocrinologists of the Department of Pediatrics and the Endocrinology and Metabolism Department of the Puerta del Mar University Hospital, as previously described [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

“…Biochemical analysis was performed in serum or plasma by standard clinical assays in the Clinical Analysis Department at Puerta del Mar University Hospital. Glucose, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides (TG), insulin, aspartate transaminase activity (GOT), alanine transaminase activity (GPT), and z-scores were measured as described before [ 20 ]. Insulin resistance was defined as before [ 20 ], according to the ADA criteria: a HOMA-IR above 3.5, fasting insulin > 15 µUI/mL, insulin at 120′ of OGTT > 75 µUI/mL, or insulin at any time point of the curve > 150 µUI/mL.…”

Section: Methodsmentioning

confidence: 99%

Proinflammatory Polyphosphate Increases in Plasma of Obese Children with Insulin Resistance and Adults with Severe Type 2 Diabetes

et al. 2022

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Obesity increases the risk of insulin resistance and type 2 diabetes through increased inflammation at cellular and tissue levels. Therefore, study of the molecular elements involved in obesity-related inflammation may contribute to preventing and controlling it. Inorganic polyphosphate is a natural phosphate polymer that has recently been attracting more attention for its role in inflammation and hemostasis processes. Polyphosphates are one of the main constituents of human platelets, which are secreted after platelet activation. Among other roles, they interact with multiple proteins of the coagulation cascade, trigger bradykinin release, and inhibit the complement system. Despite its importance, determinations of polyphosphate levels in blood plasma had been elusive until recently, when we developed a method to detect these levels precisely. Here, we perform cross sectional studies to evaluate plasma polyphosphate in: 25 children, most of them with obesity and overweight, and 20 adults, half of them with severe type 2 diabetes. Our results show that polyphosphate increases, in a significant manner, in children with insulin resistance and in type 2 diabetes patients. As we demonstrated before that polyphosphate decreases in healthy overweight individuals, these results suggest that this polymer could be an inflammation biomarker in the metabolic disease onset before diabetes.

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“…2 Thus, it has been described that children with obesity exhibit a marked proinflammatory status (i.e., raised production of cytokines, abnormal white blood cell counts) 3 and altered redox metabolism, this latter characterized by increased levels of lipid and protein oxidation markers as well as by impaired antioxidant defense. 4,5 Moreover, obesity is also known to alter puberty progression, and puberty to influence obesityrelated complications. Indeed, sexual hormones are important regulators of adipose tissue differentiation and distribution.…”

Section: Introductionmentioning

confidence: 99%

“…In this respect, oxidative stress and chronic low‐grade inflammation have been proposed as pivotal molecular drivers of many of these obesity‐related disorders 2 . Thus, it has been described that children with obesity exhibit a marked pro‐inflammatory status (i.e., raised production of cytokines, abnormal white blood cell counts) 3 and altered redox metabolism, this latter characterized by increased levels of lipid and protein oxidation markers as well as by impaired antioxidant defense 4,5 . Moreover, obesity is also known to alter puberty progression, and puberty to influence obesity‐related complications.…”

Section: Introductionmentioning

confidence: 99%

Trace elements as potential modulators of puberty‐induced amelioration of oxidative stress and inflammation in childhood obesity

et al. 2023

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Although puberty is known to influence obesity progression, the molecular mechanisms underlying the role of sexual maturation in obesity‐related complications remains largely unexplored. Here, we delve into the impact of puberty on the most relevant pathogenic hallmarks of obesity, namely oxidative stress and inflammation, and their association with trace element blood status. To this end, we studied a well‐characterized observational cohort comprising prepubertal (N = 46) and pubertal (N = 48) children with obesity. From all participants, plasma and erythrocyte samples were collected and subjected to metallomics analysis and determination of classical biomarkers of oxidative stress and inflammation. Besides the expected raise of sexual hormones, pubertal children displayed better inflammatory and oxidative control, as reflected by lower levels of C‐reactive protein and oxidative damage markers, as well as improved antioxidant defense. This was in turn accompanied by a healthier multielemental profile, with increased levels of essential elements involved in the antioxidant system and metabolic control (metalloproteins containing zinc, molybdenum, selenium, and manganese) and decreased content of potentially deleterious species (total copper, labile free iron). Therefore, our findings suggest that children with obesity have an exacerbated inflammatory and oxidative damage at early ages, which could be ameliorated during pubertal development by the action of trace element‐mediated buffering mechanisms.

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Catalase post-translational modifications as key targets in the control of erythrocyte redox homeostasis in children with obesity and insulin resistance

Cited by 12 publications

References 37 publications

Altered Insulin Secretion Dynamics Relates to Oxidative Stress and Inflammasome Activation in Children with Obesity and Insulin Resistance

Altered Insulin Secretion Dynamics Relates to Oxidative Stress and Inflammasome Activation in Children with Obesity and Insulin Resistance

Proinflammatory Polyphosphate Increases in Plasma of Obese Children with Insulin Resistance and Adults with Severe Type 2 Diabetes

Trace elements as potential modulators of puberty‐induced amelioration of oxidative stress and inflammation in childhood obesity

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