Obesity, Inflammation, and Prostate Cancer

Fujita, Kazutoshi; Hayashi, Takuji; Matsushita, Makoto; Uemura, Mamoru; Nonomura, Norio

doi:10.3390/jcm8020201

Cited by 95 publications

(67 citation statements)

References 81 publications

(89 reference statements)

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“…Moreover, other studies reported that TNF-α is overexpressed in the adipose tissue of obese individuals [28], and this cytokine activates neuronal cytokine receptors (e.g., TNF-α receptor) that cause aberrant activation of stress-sensitive kinases (c-Jun N-terminal kinase; JNK, IkBα kinase; IKK and double-stranded RNA-dependent protein kinase; PKR), leading to insulin resistance [27,29]. Therefore, in obesity, both adipose-tissue-derived pro-inflammatory mediators and cytokines produced by CNS-resident microglia exacerbate neuronal inflammation [26], which is a common feature of AD [69]. Accordingly, our immunoblot and immunofluorescence results also indicated that HFD leads to activation of stress kinase (JNK) and neuroinflammatory markers (TNFα and IL-1 β) in HFD-fed mouse brain (Figure 4c,d).…”

Section: Discussionmentioning

confidence: 99%

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer’s Like Pathology in Mice Brain

Hahm

Ullah

et al. 2020

Cells

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Oxidative stress and insulin resistance play major roles in numerous neurodegenerative diseases, including Alzheimer’s disease (AD). A high-fat diet induces obesity-associated oxidative stress, neuronal insulin resistance, microglial activation, and neuroinflammation, which are considered important risk factors for neurodegeneration. Obesity-related metabolic dysfunction is a risk factor for cognitive decline. The present study aimed to elucidate whether chronic consumption of a high-fat diet (HFD; 24 weeks) can induce insulin resistance, neuroinflammation, and amyloid beta (Aβ) deposition in mouse brains. Male C57BL/6N mice were used for a high-fat diet (HFD)-induced pre-clinical model of obesity. The protein expression levels were examined via Western blot, immunofluorescence, and the behavior analysis was performed using the Morris water maze test. To obtain metabolic parameters, insulin sensitivity and glucose tolerance tests were performed. We found that metabolic perturbations from the chronic consumption of HFD elevated neuronal oxidative stress and insulin resistance through adiponectin receptor (AdipoR1) suppression in HFD-fed mice. Similarly, our in vitro results also indicated that knockdown of AdipoR1 in the embryonic mouse hippocampal cell line mHippoE-14 leads to increased oxidative stress in neurons. In addition, HFD markedly increased neuroinflammatory markers’ glial activation in the cortex and hippocampus regions of HFD mouse brains. More importantly, we observed that AdipoR1 suppression increased the amyloidogenic pathway both in vivo and in vitro. Furthermore, deregulated synaptic proteins and behavioral deficits were observed in the HFD mouse brains. Taken together, our findings suggest that excessive consumption of an HFD has a profound impact on brain function, which involves the acceleration of cognitive impairment due to increased obesity-associated oxidative stress, insulin resistance, and neuroinflammation, which ultimately may cause early onset of Alzheimer’s pathology via the suppression of AdipoR1 signaling in the brain.

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Section: Discussionmentioning

confidence: 99%

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer’s Like Pathology in Mice Brain

Hahm

Ullah

et al. 2020

Cells

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“…Inflammation is a well‐known process in many infectious and noninfectious diseases 34‐36 . Mitochondrial dysfunction and amplified ROS production are key events in inflammatory diseases and are responsible for the association between chronic inflammation and increased tumor incidence 37,38 .…”

Section: Discussionmentioning

confidence: 99%

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

et al. 2020

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oxygen species; TLR, toll-like receptor; TRAF3, tumor necrosis factor receptorassociated factor 3; ULK1, Unc-51 like autophagy activating kinase 1. AbstractDisrupted mitochondrial function and reactive oxygen species (ROS) generation cause cellular damage and oxidative stress-induced macrophage inflammatory cell death. It remains unclear how mitochondrial dysfunction relates to inflammasome activation and pyroptotic cell death. In this study, we demonstrated that tumor necrosis factor receptor-associated factor 3 (TRAF3) regulates mitochondrial ROS production and promotes TLR agonist LPS plus nigericin (LPS/Ng)-induced inflammasome and pyroptosis in mouse primary macrophages and human monocyte THP-1 cells. Co-IP assays confirmed that TRAF3 forms a complex with TRAF2 and cIAP1 and mediates ubiquitin and degradation of Unc-51 like autophagy activating kinase 1 (ULK1). Moreover, knockdown of ULK1 in THP-1 cells significantly promoted LPS/Ng-induced inflammasome by activating caspase 1 and mature IL-1β. Apoptosis inducing factor (AIF) translocation from mitochondrial to nuclear was observed in ULK1-deficient THP-1 cells under LPS/Ng stimulation, which mediates LPS/Ng-induced cell death in ULK1 deficient macrophages. In conclusion, this study identified a novel role of TRAF3 in regulation of ULK1 ubiquitination and inflammasome signaling and provided molecular mechanisms by which ubiquitination of ULK1 controls mitochondrial ROS production, inflammasome activity, and AIF-dependent pyroptosis. K E Y W O R D S cell death, inflammasome, macrophages, mitochondrial, reactive oxygen species | 7145 SHEN Et al.

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“…Obesity is reportedly associated with various cancers, including PCa [10,11] and is an independent predictor of PCa according to a prospective study of 3673 men in the United States [RR = 1.7 for body mass index (BMI) > 27.8 kg/m 2 vs. BMI < 23.6 kg/m 2 ] [12]. Additionally, several epidemiological studies strongly suggest obesity is associated with progression in advanced PCa [13]. The prevalence of obesity varies significantly across regions, ranging from almost 40% in the United States to <~10% in Asian countries [14].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, regional differences in obesity rates might contribute to differences in the incidence of high-risk PCa. Moreover, obesity resulting from a high-calorie diet causes chronic systemic inflammation and might be involved in PCa growth through immune system-related mechanisms [13,15].…”

Section: Introductionmentioning

confidence: 99%

Influence of Diet and Nutrition on Prostate Cancer

Matsushita

Fujita

Nonomura

2020

IJMS

Self Cite

108

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The incidence of prostate cancer (PCa) displays widespread regional differences, probably owing to differences in dietary habits. Nutrients, including fat, protein, carbohydrates, vitamins (vitamin A, D, and E), and polyphenols, potentially affect PCa pathogenesis and progression, as previously reported using animal models; however, clinical studies have reported controversial results for almost all nutrients. The effects of these nutrients may be manifested through various mechanisms including inflammation, antioxidant effects, and the action of sex hormones. Dietary patterns including the Western and Prudent patterns also influence the risk of PCa. Recent studies reported that the gut microbiota contribute to tumorigenesis in some organs. Diet composition and lifestyle have a direct and profound effect on the gut bacteria. Human studies reported an increase in the abundance of specific gut bacteria in PCa patients. Although there are few studies concerning their relationship, diet and nutrition could influence PCa, and this could be mediated by gut microbiota. An intervention of dietary patterns could contribute to the prevention of PCa. An intervention targeting dietary patterns may thus help prevent PCa.

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Obesity, Inflammation, and Prostate Cancer

Cited by 95 publications

References 81 publications

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer’s Like Pathology in Mice Brain

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer’s Like Pathology in Mice Brain

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

Influence of Diet and Nutrition on Prostate Cancer

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