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Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death, and adipose tissue inflammation in high fat-fed mice.

ABSTRACT: Obesity is associated with enhanced reactive oxygen species (ROS) accumulation in adipose tissue. However, a causal role for ROS in adipose tissue expansion after high fat feeding is not established. The aim of this study is to investigate the effect of the cell permeable superoxide dismutase mimetic and peroxynitrite scavenger Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) on adipose tissue expansion and remodeling in response to high fat diet (HFD) in mice.Male C57BL/6j mice were fed normal chow or high fat diet (HFD) and treated with saline or MnTBAP for 5 weeks. The effects of MnTBAP on body weights, whole body energy expenditure, adipose tissue morphology, and gene expression were determined.MnTBAP attenuated weight gain and adiposity through a reduction in adipocyte hypertrophy, adipogenesis, and fatty acid uptake in epididymal (eWAT) but not in inguinal (iWAT) white adipose tissue. Furthermore, MnTBAP reduced adipocyte death and inflammation in eWAT and diminished circulating levels of free fatty acids and leptin. Despite these improvements, the development of systemic insulin resistance and diabetes after HFD was not prevented with MnTBAP treatment.Taken together, these data suggest a causal role for ROS in the development of diet-induced visceral adiposity but not in the development of insulin resistance and type 2 diabetes.

SUBMITTER: Pires KM

PROVIDER: S-EPMC3758415 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death, and adipose tissue inflammation in high fat-fed mice.

Pires Karla M KM Ilkun Olesya O Valente Marina M Boudina Sihem S

Obesity (Silver Spring, Md.) 20130613 1

<h4>Objective</h4>Obesity is associated with enhanced reactive oxygen species (ROS) accumulation in adipose tissue. However, a causal role for ROS in adipose tissue expansion after high fat feeding is not established. The aim of this study is to investigate the effect of the cell permeable superoxide dismutase mimetic and peroxynitrite scavenger Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) on adipose tissue expansion and remodeling in response to high fat diet (HFD) in mice.<h4>Des ...[more]

PMID: 23526686

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Project description:BackgroundObesity-induced glucose metabolism disorder is associated with chronic, low-grade, systemic inflammation and is considered a risk factor for diabetes and metabolic syndrome. Resveratrol (RES), a natural anti-inflammatory compound, is observed to improve glucose tolerance and insulin sensitivity in obese rodents and humans. This study aimed to test the effects of RES administration on insulin signaling and the inflammatory response in visceral white adipose tissue (WAT) caused by a high-fat diet (HFD) in mice.MethodsA total of 40 wild-type C57BL/6 male mice were divided into four groups (10 in each group): the standard chow diet (STD) group was fed a STD; the HFD group was fed a HFD; and the HFD-RES/L and HFD-RES/H groups were fed a HFD plus RES (200 and 400 mg/kg/day, respectively). The L and H in RES/L and RES/H stand for low and high, respectively. Glucose tolerance, insulin sensitivity, circulating inflammatory biomarkers and lipid profile were determined. Quantitative PCR and Western blot were used to determine the expression of CC-chemokine receptor 2 (CCR2), other inflammation markers, glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and pAkt/Akt and to assess targets of interest involving glucose metabolism and inflammation in visceral WAT.ResultsHFD increased the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and proinflammatory cytokines in serum, decreased the high-density lipoprotein cholesterol level in serum, and induced insulin resistance and WAT inflammation in mice. However, RES treatment alleviated insulin resistance, increased the expressions of pAkt, GLUT4 and IRS-1 in WAT, and decreased serum proinflammatory cytokine levels, macrophage infiltration and CCR2 expression in WAT.ConclusionOur results indicated that WAT CCR2 may play a vital role in macrophage infiltration and the inflammatory response during the development of insulin resistance in HFD-induced obesity. These data suggested that administration of RES offers protection against abnormal glucose metabolism and inflammatory adaptations in visceral WAT in mice with HFD-induced obesity.

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Dataset Information

Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death, and adipose tissue inflammation in high fat-fed mice.

Publications

Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death, and adipose tissue inflammation in high fat-fed mice.

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