Hyperuricemia as a Mediator of the Proinflammatory Endocrine Imbalance in the Adipose Tissue in a Murine Model of the Metabolic Syndrome

Baldwin, William S.; McRae, Steven; Marek, George; Wymer, David C.; Pannu, Varinderpal; Baylis, Chris; Johnson, Richard J.; Sautin, Yuri Y.

doi:10.2337/db10-0916

Cited by 381 publications

(358 citation statements)

References 55 publications

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“…43 It is therefore clear that adiponectin is, overall, a potently renoprotective protein. The increased levels observed in CKD may be the result of metabolic changes in adipose tissue 44,45 and probably represent a compensatory upregulation over the course of CKD, without which CKD could take a more rapid negative outcome. The aforementioned conclusions are based on our past in vivo work with the ATTAC cassette in which cell-specific apoptosis was unambiguously demonstrated in wild-type, adiponectin KO, and adiponectin Tg backgrounds.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Promotes Functional Recovery after Podocyte Ablation

Rutkowski

Wang²,

Park

et al. 2013

Journal of the American Society of Nephrology

147

119

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Low levels of the adipocyte-secreted protein adiponectin correlate with albuminuria in both mice and humans, but whether adiponectin has a causative role in modulating renal disease is unknown. Here, we first generated a mouse model that allows induction of caspase-8-mediated apoptosis specifically in podocytes upon injection of a construct-specific agent. These POD-ATTAC mice exhibited significant kidney damage, mimicking aspects of human renal disease, such as foot process effacement, mesangial expansion, and glomerulosclerosis. After the initial induction, both podocytes and filtration function recovered. Next, we crossed POD-ATTAC mice with mice lacking or overexpressing adiponectin. POD-ATTAC mice lacking adiponectin developed irreversible albuminuria and renal failure; conversely, POD-ATTAC mice overexpressing adiponectin recovered more rapidly and exhibited less interstitial fibrosis. In conclusion, these results suggest that adiponectin is a renoprotective protein after podocyte injury. Furthermore, the POD-ATTAC mouse provides a platform for further studies, allowing precise timing of podocyte injury and regeneration.

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Section: Discussionmentioning

confidence: 99%

Adiponectin Promotes Functional Recovery after Podocyte Ablation

Rutkowski

Wang²,

Park

et al. 2013

Journal of the American Society of Nephrology

147

119

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“…Uric acid has been shown to contribute to lipoprotein oxidation and inflammation (11,18). Lanaspa et al (10) provided the first direct evidence that uric acid stimulated fat synthesis in the hepatocytes and in the pound mouse.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, lowering uric acid in obese mice decreased macrophage infiltration in the adipose tissue and reduced insulin resistance. Hyperuricemia may be partially responsible for the inflammation in the adipose tissue (11). A recent study demonstrated that uric acid crystals induced pro-inflammatory effects (20).…”

Section: Discussionmentioning

confidence: 99%

“…Elevation in SUA levels independently predicts an increase in the risk for the incident of NAFLD and suggests that high SUA levels may have a causal role in the development of NAFLD (9). Certain in vitro and in vivo studies in hepatocytes and liver tissue of mice suggest that uric acid stimulated fat synthesis and induced inflammatory cell infiltration in the liver (10,11). Therefore, it is plausible that uric acid may reflect increased disease severity in NAFLD.…”

Section: Introductionmentioning

confidence: 99%

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Association of the serum uric acid level with liver histology in biopsy-proven non-alcoholic fatty liver disease

Huang

Zhang

et al. 2016

Biomedical Reports

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Abstract. Hyperuricemia is significantly associated with and independently predicts the risk for non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to examine the association of serum uric acid (SUA) levels with liver histology in patients with biopsy-proven NAFLD. Data were collected from 158 adults aged >18 years, and diagnosed with biopsy-proven NAFLD. The differences in liver histology were assessed between hyperuricemic and normal SUA groups with NAFLD to determine the possible risk factors. The SUA level was closely associated with the degree of steatosis (correlation coefficient 0.177, P= 0.027). A higher proportion of patients with hyperuricemia showed increased severity of lobular inflammation (lobular inflammation score ≥2) compared with patients exhibiting normal SUA (75 vs. 52.7%; χ 2 =8.548, P=0.003). Hyperuricemic groups had higher non-alcoholic steatosis (≥5) compared to the normal SUA groups with NAFLD (48.8 vs. 31.1%; χ 2 =5.131, P=0.024). Hyperuricemia was independently associated with advanced lobular inflammation (odds ratio, 2.79; 95% confidence interval, 1.250-6.257; P= 0.012) using a logistic regression model controlling for ferritin, serum alanine aminotransferase and aspartate aminotransferase. In conclusion, hyperuricemia is associated with histologically severe NAFLD. Hyperuricemia was independently associated with greater odds of advanced lobular inflammation of NAFLD. IntroductionNon-alcoholic fatty liver disease (NAFLD) is a state of intrahepatic fat accumulation, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the most common liver disease in Western countries, affecting 20-30% of the general population (1). NAFLD is also an emerging public health concern in developing countries (2,3). Among more affluent regions of China, the community prevalence of NAFLD is 15% (2). With the increasing obesity pandemic, the prevalence of NAFLD is likely to increase in the future (2). Serum uric acid (SUA) levels are closely associated with insulin resistance, diabetes mellitus type 2 and metabolic syndrome (4,5). Hyperuricemia was significantly associated with NAFLD, and the prevalence of NAFLD increases with SUA increase (6-8). Elevation in SUA levels independently predicts an increase in the risk for the incident of NAFLD and suggests that high SUA levels may have a causal role in the development of NAFLD (9). Certain in vitro and in vivo studies in hepatocytes and liver tissue of mice suggest that uric acid stimulated fat synthesis and induced inflammatory cell infiltration in the liver (10,11). Therefore, it is plausible that uric acid may reflect increased disease severity in NAFLD. However, there is one previous study regarding the association between UA serum levels and histological severity of NAFLD patients (12). The majority of studies have been conducted in Western populations. Notably, the prevalence of obesity in China is significantly lower compared to Western countries (13,14), and certain features of metabolic ...

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“…Hyperuricemia, which is strongly associated with obesity and MetS and nephropathy can predict visceral obesity and insulin resistance, might be partially responsible for the pro-inflammatory endocrine imbalance in the adipose tissue, which is an underlying mechanism of the lowgrade inflammation and insulin resistance in subjects with the MetS [60][61][62][63][64][65]. Gout is a common metabolic disorder, involving the liver, kidney, and joints; it is met more often in men, and is characterized by the deposition of reversible monosodium urate (MSU) crystals and occurs as a consequence of hyperuricemia which induces inflammatory arthritis and nephropathy.…”

Section: Mets Hyperuricemia and Nephropathymentioning

confidence: 99%

Efficacy of Fenugreek-based bionanocomposite on renal dysfunction and endogenous intoxication in high-calorie diet-induced obesity rat model—comparative study

et al. 2017

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Background Worldwide obesity spread is a global health problem and needs to be further studied. Co-morbidities of obesity include insulin resistance, diabetes mellitus type 2, and dyslipidemia, which are the most frequent contributing factors for metabolic syndrome (MetS), as well as nonalcoholic fatty liver disease and chronic kidney disease. The aim was to study renal function and endogenous intoxication panel on high-calorie diet-induced obesity rat model and perform comparative study of the treatment efficacy of Fenugreek-based bionanocomposite vs antiobesogenic drugs (Orlistat). Materials We included 60 male rats and equally divided them to 6 groups of 10 animals in each group: the experimental groups were firstly assigned as controls and high caloric diet (HCD)-fed groups, and each group further was subdivided to remain untreated, Fenugreek bionanocomposite (BNC)-treated, and Orlistat-treated. Normal control rats (groups 1, 2, 3) were fed by a standard chow, while the others (groups 4, 5, 6) were fed with HCD ad libitum during 98 days. From days 77 to 98, groups 2 and 5 were treated with BNC based on Fenugreek (150 mg/kg body weight, orally) and groups 3 and 6 were treated with antiobesogenic drug Orlistat (10 mg/kg body weight, orally). Food and water consumptions were measured daily and body weights were measured once a week. On day 99, blood was collected; the creatinine, urea, and uric acid were estimated in serum according to the standard protocols. Levels of low and middle molecules (MMs) were measured; the quantity of oligopeptides was estimated by Bradford method. We performed the liver and kidney ultrasonography in rats.Results We revealed an increase in the levels of endogenous intoxication syndrome markers (MM and oligopeptides) in all animals with experimental obesity. Ultrasound data showed injury of the liver and kidneys in obese rats. We observed significant decreasing of MM levels after Orlistat treatment vs controls (p < 0.05). However, this effect was more pronounced in Fenugreek BNC-treated group vs both Orlistattreated and controls (p < 0.05). Orlistat treatment evoked rising of serum creatinine and oligopeptides in control animals

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Hyperuricemia as a Mediator of the Proinflammatory Endocrine Imbalance in the Adipose Tissue in a Murine Model of the Metabolic Syndrome

Cited by 381 publications

References 55 publications

Adiponectin Promotes Functional Recovery after Podocyte Ablation

Adiponectin Promotes Functional Recovery after Podocyte Ablation

Association of the serum uric acid level with liver histology in biopsy-proven non-alcoholic fatty liver disease

Efficacy of Fenugreek-based bionanocomposite on renal dysfunction and endogenous intoxication in high-calorie diet-induced obesity rat model—comparative study

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