The initiation of metabolic inflammation in childhood obesity

Singer, Kanakadurga; Lumeng, Carey N.

doi:10.1172/jci88882

Cited by 143 publications

(144 citation statements)

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“…Obesity increases de novo lipogenesis, inducing hepatic steatosis and NAFLD [12]. Excessive lipid accumulation in the hepatic tissue obstructs the normal physiological function of hepatocytes, and induced insulin resistance, inflammation, and peroxidation can cause the development of chronic liver fibrosis and hepatic cancer [22,23]. Many studies have found that reducing lipid accumulation can decrease liver inflammation and fibrosis in NAFLD, even allowing for the possibility of a return to normal liver function and lipogenesis, (B) the Sirt-1/AMPK pathway, and (C) lipolysis-and β-oxidation-associated proteins detected by western blot.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Ginkgolide B reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease in high-fat dietâ€“induced obese mice

Wang¹,

Liou²,

Wu³

et al. 2018

Oncotarget

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Ginkgolide B is isolated from Ginkgo biloba leaves. It has multiple biological functions, including alleviating lung injury and ischemic stroke in mice and protecting pancreatic beta cells and improving endothelial dysfunction in diabetic mice. Here we sought to determine whether ginkgolide B ameliorates nonalcoholic fatty liver disease (NALFD) in high-fat diet (HFD)-induced obese mice. We also evaluated whether or not ginkgolide B reduces lipid accumulation of hepatocytes in vitro. C57BL/6 mice were fed with HFD and treated with ginkgolide B by intraperitoneal injection twice a week for last 10 weeks of the 14-week HFD feeding period. In addition, HepG2 cells were treated with oleic acid to establish a fatty liver cell model and exposed to various concentrations of ginkgolide B. Ginkgolide B significantly decreased hepatic lipid accumulation and alleviated steatosis in HFD-induced obese mice. It also reduced body weight and epididymal adipose tissue weight. Serum assay results showed that ginkgolide B inhibited leptin, alanine aminotransferase, and aspartate aminotransferase levels and increased HDL levels compared to obese mice. It also decreased fatty acid synthase expression and increased Sirt-1 and phosphorylation of AMP-activated protein kinase α in liver tissue. Furthermore, ginkgolide B significantly inhibited lipid accumulation and expression of adipogenesis-related proteins and increased adipolysis-associated protein expression in hepatocytes in vitro. These results suggest that ginkgolide B is an effective natural compound for alleviating hepatic lipid accumulation and reducing body weight in obese mice. It also ameliorated NALFD in HFD-induced obese mice. www.impactjournals.com/oncotarget/

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Ginkgolide B reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease in high-fat dietâ€“induced obese mice

Wang¹,

Liou²,

Wu³

et al. 2018

Oncotarget

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“…In recent years, there has been increasing appreciation of obesity as a state of chronic inflammation in adipose tissue [26,27]. Excess adipose tissues determine the release of a variety of oxidative stress and proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Serum Calprotectin Level in Children: Marker of Obesity and its Metabolic Complications

et al. 2018

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Aim: Elevated calprotectin levels have been reported in obese adults but have not been evaluated in pediatric population. We investigated the characteristics of serum calprotectin in overweight and obese children and its association with metabolic comorbidities. Methods: We enrolled 131 children (11.7 ± 4.1 years). According to body mass index (BMI), the subjects were divided into 3 groups: obese > 95th percentile; overweight BMI 75th–95th percentile, and normal weight BMI < 75th percentile. Patients were classified as having Metabolic Syndrome if they met 3 or more of the following criteria for age and sex: BMI > 97th percentile, triglycerides > 95th percentile, high-density lipoprotein cholesterol < 5th percentile, systolic and/or diastolic blood pressure > 95th percentile, and impaired glucose tolerance. In all patients, calprotectin serum levels were also detected. Results: Calprotectin was higher in obese and overweight children than normal weight subjects (p < 0.001), with calprotectin in females being significantly higher than in males (p = 0.04). Increased calprotectin was related to pathological fasting blood glucose (p < 0.001) and insulin resistance (p = 0.03), while BMI (p = 0.001), and diastolic pressure (p = 0.001) are independent factors for increased calprotectin. Conclusions: Our findings confirm the association between increased calprotectin and obesity also in children and suggest the potential utility of this biomarker in the monitoring of its metabolic complications.

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“…While obesity is closely associated with increased inflammatory markers in liver, adipose tissue, skeletal muscle, pancreatic islets, and brain, the precise temporal relationships between these events in rodents or obese humans remain uncertain. Kanakadurga Singer and Carey Lumeng review the initiating events in obesity-induced inflammation in the context of human development, many of which are sustained into adulthood (11). Numerous mechanisms have been investigated in rodent models of dietary and genetic obesity (12,13).…”

Section: What Triggers Obesity-induced Inflammation?mentioning

confidence: 99%

Inflammatory mechanisms linking obesity and metabolic disease

Saltiel¹,

Olefsky²

2017

Journal of Clinical Investigation

1,474

1,077

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We are in the midst of a worldwide obesity epidemic. Over 1.9 billion people are now obese or overweight, including more than 50 million children under age 5, and the worldwide prevalence of obesity has doubled since 1980 (1). The complications of obesity are taking a major public health toll, which will only worsen in future years. Among the most devastating of these complications is type 2 diabetes (T2D). Most patients with T2D are obese or overweight, and there are numerous longitudinal studies linking obesity with insulin resistance, a frequent forerunner of diabetes.Over the past two decades, the search for a mechanism linking the pathogenesis of obesity with insulin resistance and diabetes has revealed a close relationship between nutrient excess and activation of the innate immune system in most organs pertinent to energy homeostasis (2-4). Numerous studies indicate that inflammation occurs as a consequence of obesity, and recent insights suggest that it may play a causative role in generating insulin resistance, defective insulin secretion, and disruption of other aspects of energy homeostasis. The nature of obesityinduced inflammation differs from other inflammatory paradigms in that it involves tonic activation of the innate immune system that impacts metabolic homeostasis, in some cases over a lifetime. Inflammation also leads to maladaptive responses such as fibrosis and necrosis that can cause significant tissue damage. Moreover, obesity-induced inflammation is unique in that it involves multiple organs, including adipose, pancreas, liver, skeletal muscle, heart, and brain. These features of obesity-induced inflammation present a challenge to understanding the underlying mechanisms and the manner by which they impact metabolic systems. In this issue of the JCI, a group of experts have provided reviews that dive deeply into the mechanisms by which obesity-induced inflammation influences metabolic homeostasis, surveying the modes and mechanisms of inflammation in different tissues and how they might contribute to disease. These Reviews also discuss how inflammation can lead to other aspects of metabolic syndrome, including hyperphagia, reduced energy expenditure, β cell dysfunction, and liver disease, and summarize the status of therapeutic interventions that target inflammation in the context of metabolic syndrome. Activation of the innate immune system in obesityMuch of what has been learned about the immune response to obesity has come from studies in adipose tissue, although it is clear that inflammation occurs in other organs as well. Adipose depots normally contain multiple immune cells that together surveil and maintain the integrity and hormonal sensitivity of adipocytes. In lean animals, these immune cells operate in an overall Th2 or type 2 state that coordinately controls tissue integrity and metabolism by controlling the activity of subsets of T lymphocytes. These cells release a cascade of cytokines that coordinately regulate other immune cells, including eosinophils, mast cells, and othe...

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The initiation of metabolic inflammation in childhood obesity

Cited by 143 publications

References 146 publications

WITHDRAWN: Ginkgolide B reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease in high-fat dietâ€“induced obese mice

WITHDRAWN: Ginkgolide B reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease in high-fat dietâ€“induced obese mice

Serum Calprotectin Level in Children: Marker of Obesity and its Metabolic Complications

Inflammatory mechanisms linking obesity and metabolic disease

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