Uric Acid‐Induced Adipocyte Dysfunction Is Attenuated by HO‐1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity

Sodhi, Komal; Hilgefort, Jordan; Banks, George C.; Gilliam, Chelsea; Stevens, Sarah; Ansinelli, Hayden; Getty, Morghan; Abraham, Nader G.; Shapiro, Joseph I.; Khitan, Zeid

doi:10.1155/2016/8197325

Cited by 20 publications

(19 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This process occurs in hepatocytes, enterocytes, muscle cells and proximal tubule renal cells. In adipocytes, there is some indirect evidence of the activity of this pathway [88]. For example, in MSC-derived adipocytes, incubation with 500 mM fructose significantly increased xanthine oxidase expression as well as uric acid concentrations.…”

Section: Uric Acid Resulting From Fructose Metabolism As a Mediatomentioning

confidence: 99%

“…Moreover, incubation with UA (5 mg/dL) also increased adipogenesis by 50%, augmented the number of large lipid droplets, and decreased the number of small droplets compared to the control. In addition, UA also increased the mRNA of C/EBPα and PPARγ, known mediators of adipocyte hyperplasia [88]. XOR is an enzyme that catalyzes the catabolism of purines such as xanthine and hypoxanthine to uric acid [89].…”

Section: Uric Acid Resulting From Fructose Metabolism As a Mediatomentioning

confidence: 99%

See 1 more Smart Citation

High Fructose Intake and Adipogenesis

Hernández-Díazcouder

Romero‐Nava

Carbó

et al. 2019

IJMS

View full text Add to dashboard Cite

In modern societies, high fructose intake from sugar-sweetened beverages has contributed to obesity development. In the diet, sucrose and high fructose corn syrup are the main sources of fructose and can be metabolized in the intestine and transported into the systemic circulation. The liver can metabolize around 70% of fructose intake, while the remaining is metabolized by other tissues. Several tissues including adipose tissue express the main fructose transporter GLUT5. In vivo, chronic fructose intake promotes white adipose tissue accumulation through activating adipogenesis. In vitro experiments have also demonstrated that fructose alone induces adipogenesis by several mechanisms, including (1) triglycerides and very-low-density lipoprotein (VLDL) production by fructose metabolism, (2) the stimulation of glucocorticoid activation by increasing 11β-HSD1 activity, and (3) the promotion of reactive oxygen species (ROS) production through uric acid, NOX and XOR expression, mTORC1 signaling and Ang II induction. Moreover, it has been observed that fructose induces adipogenesis through increased ACE2 expression, which promotes high Ang-(1-7) levels, and through the inhibition of the thermogenic program by regulating Sirt1 and UCP1. Finally, microRNAs may also be involved in regulating adipogenesis in high fructose intake conditions. In this paper, we propose further directions for research in fructose participation in adipogenesis.

show abstract

Section: Uric Acid Resulting From Fructose Metabolism As a Mediatomentioning

confidence: 99%

Section: Uric Acid Resulting From Fructose Metabolism As a Mediatomentioning

confidence: 99%

High Fructose Intake and Adipogenesis

Hernández-Díazcouder

Romero‐Nava

Carbó

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…The restoration of the metabolic parameters was mirrored by the normalization of the adipogenic markers FAS, aP2, PEG1/MEST, and C/EBP α , as well as the reduction of inflammation (TNF α and IL-6) in visceral fat obtained from EET-A-treated mice fed a HF diet as compared to the obese control mice. The normalization of adipogenic and inflammatory markers in HF diet fed mice treated with EET-A was coupled with increased levels of adiponectin and HO-1, both key to the maintenance of adipocyte maturation in favor of early-stage adipocyte differentiation, that is, healthy adipocytes [8, 58, 60–62]. …”

Section: Discussionmentioning

confidence: 99%

Downregulation of PGC-1αPrevents the Beneficial Effect of EET-Heme Oxygenase-1 on Mitochondrial Integrity and Associated Metabolic Function in Obese Mice

Singh

Bellner

Vanella

et al. 2016

Journal of Nutrition and Metabolism

Self Cite

View full text Add to dashboard Cite

Background/Objectives. Obesity and metabolic syndrome and associated adiposity are a systemic condition characterized by increased mitochondrial dysfunction, inflammation, and inhibition of antioxidant genes, HO-1, and EETs levels. We postulate that EETs attenuate adiposity by stimulating mitochondrial function and induction of HO-1 via activation of PGC-1α in adipose and hepatic tissue. Methods. Cultured murine adipocytes and mice fed a high fat (HF) diet were used to assess the functional relationship among EETs, PGC-1α, HO-1, and mitochondrial signaling using an EET-agonist (EET-A) and PGC-1α-deficient cells and mice using lentiviral PGC-1α(sh). Results. EET-A is a potent inducer of PGC-1α, HO-1, mitochondrial biogenesis (cytochrome oxidase subunits 1 and 4 and SIRT3), fusion proteins (Mfn 1/2 and OPA1) and fission proteins (DRP1 and FIS1) (p < 0.05), fasting glucose, BW, and blood pressure. These beneficial effects were prevented by administration of lenti-PGC-1α(sh). EET-A administration prevented HF diet induced mitochondrial and dysfunction in adipose tissue and restored VO2 effects that were abrogated in PGC-1α-deficient mice. Conclusion. EET is identified as an upstream positive regulator of PGC-1α that leads to increased HO-1, decreased BW and fasting blood glucose and increased insulin receptor phosphorylation, that is, increased insulin sensitivity and mitochondrial integrity, and possible use of EET-agonist for treatment of obesity and metabolic syndrome.

show abstract

“…Heme oxygenase 1 (HO1), a potent antioxidant, decreases UA levels and adipocyte dysfunction by decreasing levels of ROS and XO [73]. XO is one of the major endothelial sources of O 2 − and H 2 O 2 .…”

Section: Mechanisms By Which Fructose-uric Acid May Contribute To mentioning

confidence: 99%

Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

et al. 2017

View full text Add to dashboard Cite

There is a direct relationship between fructose intake and serum levels of uric acid (UA), which is the final product of purine metabolism. Recent preclinical and clinical evidence suggests that chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, and cardiovascular disease. It is probably also an independent risk factor for chronic kidney disease, Type 2 diabetes, and cognitive decline. These relationships have been observed for high serum UA levels (>5.5 mg/dL in women and >6 mg/dL in men), but also for normal to high serum UA levels (5–6 mg/dL). In this regard, blood UA levels are much higher in industrialized countries than in the rest of the world. Xanthine-oxidase inhibitors can reduce UA and seem to minimize its negative effects on vascular health. Other dietary and pathophysiological factors are also related to UA production. However, the role of fructose-derived UA in the pathogenesis of cardiometabolic disorders has not yet been fully clarified. Here, we critically review recent research on the biochemistry of UA production, the relationship between fructose intake and UA production, and how this relationship is linked to cardiometabolic disorders.

show abstract

Uric Acid‐Induced Adipocyte Dysfunction Is Attenuated by HO‐1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity

Cited by 20 publications

References 34 publications

High Fructose Intake and Adipogenesis

High Fructose Intake and Adipogenesis

Downregulation of PGC-1αPrevents the Beneficial Effect of EET-Heme Oxygenase-1 on Mitochondrial Integrity and Associated Metabolic Function in Obese Mice

Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

Contact Info

Product

Resources

About