Increased oxidative stress in obesity and its impact on metabolic syndrome

Furukawa, Shigetada; Fujita, Takuya; Shimabukuro, Michio; Iwaki, Masanori; Yamada, Yukio; Nakajima, Yutaka; Numata, Osamu; Makishima, Makoto; Matsuda, Morihiro; Shimomura, Iichiro

doi:10.1172/jci21625

Cited by 4,405 publications

(3,004 citation statements)

References 72 publications

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“…In general, increased oxidative stress in WAT can cause dysregulated production of adipokines. Additionally, increased ROS production in WAT can lead to increased oxidative stress in the blood, causing harmful events to occur in various other organs (Furukawa et al ., 2004). Certain genetically modified animals living longer than controls were reported to exhibit activated mitochondrial biogenesis in WAT (Chiu et al ., 2004; Katic et al ., 2007).…”

Section: Discussionmentioning

confidence: 99%

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

et al. 2017

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SummaryCaloric restriction (CR) can delay onset of several age‐related pathophysiologies and extend lifespan in various species, including rodents. CR also induces metabolic remodeling involved in activation of lipid metabolism, enhancement of mitochondrial biogenesis, and reduction of oxidative stress in white adipose tissue (WAT). In studies using genetically modified mice with extended lifespans, WAT characteristics influenced mammalian lifespans. However, molecular mechanisms underlying CR‐associated metabolic remodeling of WAT remain unclear. Sterol regulatory element‐binding protein‐1c (Srebp‐1c), a master transcription factor of fatty acid (FA) biosynthesis, is responsible for the pathogenesis of fatty liver (steatosis). Our study showed that, under CR conditions, Srebp‐1c enhanced mitochondrial biogenesis via increased expression of peroxisome proliferator‐activated receptor gamma coactivator‐1α (Pgc‐1α) and upregulated expression of proteins involved in FA biosynthesis within WAT. However, via Srebp‐1c, most of these CR‐associated metabolic alterations were not observed in other tissues, including the liver. Moreover, our data indicated that Srebp‐1c may be an important factor both for CR‐associated suppression of oxidative stress, through increased synthesis of glutathione in WAT, and for the prolongevity action of CR. Our results strongly suggested that Srebp‐1c, the primary FA biosynthesis‐promoting transcriptional factor implicated in fatty liver disease, is also the food shortage‐responsive factor in WAT. This indicated that Srebp‐1c is a key regulator of metabolic remodeling leading to the beneficial effects of CR.

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Section: Discussionmentioning

confidence: 99%

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

et al. 2017

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“…Its functions include supporting the lipogenesis and adipogenesis of adipocytes, thereby resulting in an excessive increase in adipose tissue [28]. Chronic obesity has been correlated with the development of liver disease owing to prolonged, mild inflammation induced by obesity [36,37]. iNOS is an inflammatory mediator that promotes the production of reactive oxygen species, NO, and endogenous signalling molecules, which contribute towards prolonging mild systemic inflammation in the liver of HFD-fed obese mice [38], which subsequently contributes to the pathogenesis of HFD-induced insulin resistance [39].…”

Section: Discussionmentioning

confidence: 99%

Dietary coconut water vinegar for improvement of obesity-associated inflammation in high-fat-diet-treated mice

Mohamad

Yeap

Kỳ

et al. 2017

Food & Nutrition Research

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Obesity has become a serious health problem worldwide. Various types of healthy food, including vinegar, have been proposed to manage obesity. However, different types of vinegar may have different bioactivities. This study was performed to evaluate the anti-obesity and anti-inflammatory effects of coconut water vinegar on high-fat-diet (HFD)-induced obese mice. Changes in the gut microbiota of the mice were also evaluated. To induce obesity, C57/BL mice were continuously fed an HFD for 33 weeks. Coconut water vinegar (0.08 and 2 ml/kg body weight) was fed to the obese mice from early in week 24 to the end of week 33. Changes in the body weight, fat-pad weight, serum lipid profile, expression of adipogenesis-related genes and adipokines in the fat pad, expression of inflammatory-related genes, and nitric oxide levels in the livers of the untreated and coconut water vinegar-treated mice were evaluated. Faecal samples from the untreated and coconut water vinegar-treated mice (2 ml/kg body weight) were subjected to 16S metagenomic analysis to compare their gut microbiota. The oral intake of coconut water vinegar significantly (p < 0.05) reduced the body weight, fat-pad weight, and serum lipid profile of the HFD-induced obese mice in a dose-dependent manner. We also observed up-regulation of adiponectin and down-regulation of sterol regulatory element-binding protein-1, retinol-binding protein-4, and resistin expression. The coconut water vinegar also reduced HFD-induced inflammation by down-regulating nuclear factor-κB and inducible nitric oxide synthase expression, which consequently reduced the nitric oxide level in the liver. Alterations in the gut microbiota due to an increase in the populations of the Bacteroides and Akkermansia genera by the coconut water vinegar may have helped to overcome the obesity and inflammation caused by the HFD. These results provide valuable insights into coconut water vinegar as a potential food ingredient with anti-obesity and anti-inflammatory effects.

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“…Several studies indicate that treatment of cultured cells with insulin, or hyperinsulinemia induced in animal models, promotes the generation of reactive oxygen species (ROS) Correspondence should be addressed to S R Sampson Email sansampson@gmail.com 230:3 (Mukherjee et al 1978, May & de Haen 1979, Goldstein et al 2005a, Barazzoni et al 2012 or superoxides (Barazzoni et al 2012). ROS, in turn, can increase oxidative stress and apoptosis in various cell types (Furukawa et al 2004), including pancreatic β cells (Robertson 2004, Eizirik et al 2008.…”

Section: Introductionmentioning

confidence: 99%

Prolonged insulin treatment sensitizes apoptosis pathways in pancreatic β cells

Bucris

Beck

Boura‐Halfon

et al. 2016

Journal of Endocrinology

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Insulin resistance results from impaired insulin signaling in target tissues that leads to increased levels of insulin required to control plasma glucose levels. The cycle of hyperglycemia and hyperinsulinemia eventually leads to pancreatic β cell deterioration and death by a mechanism that is yet unclear. Insulin induces ROS formation in several cell types. Furthermore, death of pancreatic β cells induced by oxidative stress could be potentiated by insulin. Here, we investigated the mechanism underlying this phenomenon. Experiments were done on pancreatic β cell lines (Min-6, RINm, INS-1), isolated mouse and human islets, and on cell lines derived from nonpancreatic sources. Insulin (100 nM) for 24 h selectively increased the production of ROS in pancreatic β cells and isolated pancreatic islets, but only slightly affected the expression of antioxidant enzymes. This was accompanied by a time-and dose-dependent decrease in cellular reducing power of pancreatic β cells induced by insulin and altered expression of several ER stress response elements including a significant increase in Trb3 and a slight increase in iNos. The effect on iNos did not increase NO levels. Insulin also potentiated the decrease in cellular reducing power induced by H 2 O 2 but not cytokines. Insulin decreased the expression of MCL-1, an antiapoptotic protein of the BCL family, and induced a modest yet significant increase in caspase 3/7 activity. In accord with these findings, inhibition of caspase activity eliminated the ability of insulin to increase cell death. We conclude that prolonged elevated levels of insulin may prime apoptosis and cell death-inducing mechanisms as a result of oxidative stress in pancreatic β cells.

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Increased oxidative stress in obesity and its impact on metabolic syndrome

Cited by 4,405 publications

References 72 publications

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

Dietary coconut water vinegar for improvement of obesity-associated inflammation in high-fat-diet-treated mice

Prolonged insulin treatment sensitizes apoptosis pathways in pancreatic β cells

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