Does Adiponectin Upregulation Attenuate the Severity of Acute Pancreatitis in Obesity?

Al-Azzawi, Hayder H.; Ziegler, Kerstin; Swartz-Basile, Deborah A.; Wang, Sue; Pitt, Henry A.; Zyromski, Nicholas J.

doi:10.1007/s11605-011-1583-x

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…In fact, low levels of adiponectin are associated with organ failure in patients with AP [37]. Furthermore, adiponectin protects HFD-fed mice from cerulein-induced AP and inhibits production of IL-6 in db/db mice [38], [39]. Thus, the high baseline levels of adiponectin in HFD + RGZ mice may have contributed to control the excessive elevation of IL-6 of obese mice.…”

Section: Discussionmentioning

confidence: 99%

Rosiglitazone Improves Survival and Hastens Recovery from Pancreatic Inflammation in Obese Mice

Pini

Rhodes²,

Castellanos³

et al. 2012

PLoS ONE

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Obesity increases severity of acute pancreatitis (AP) by unclear mechanisms. We investigated the effect of the PPAR-gamma agonist rosiglitazone (RGZ, 0.01% in the diet) on severity of AP induced by administration of IL-12+ IL-18 in male C57BL6 mice fed a low fat (LFD) or high fat diet (HFD), under the hypothesis that RGZ would reduce disease severity in HFD-fed obese animals. In both LFD and HFD mice without AP, RGZ significantly increased body weight and % fat mass, with significant upregulation of adiponectin and suppression of erythropoiesis. In HFD mice with AP, RGZ significantly increased survival and hastened recovery from pancreatic inflammation, as evaluated by significantly improved pancreatic histology, reduced saponification of visceral adipose tissue and less severe suppression of erythropoiesis at Day 7 post-AP. This was associated with significantly lower circulating and pancreas-associated levels of IL-6, Galectin-3, osteopontin and TIMP-1 in HFD + RGZ mice, particularly at Day 7 post-AP. In LFD mice with AP, RGZ significantly worsened the degree of intrapancreatic acinar and fat necrosis as well as visceral fat saponification, without affecting other parameters of disease severity or inflammation. Induction of AP lead to major suppression of adiponectin levels at Day 7 in both HFD and HFD + RGZ mice. In conclusion, RGZ prevents development of severe AP in obese mice even though it significantly increases adiposity, indicating that obesity can be dissociated from AP severity by improving the metabolic and inflammatory milieu. However, RGZ worsens selective parameters of AP severity in LFD mice.

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Section: Discussionmentioning

confidence: 99%

Rosiglitazone Improves Survival and Hastens Recovery from Pancreatic Inflammation in Obese Mice

Pini

Rhodes²,

Castellanos³

et al. 2012

PLoS ONE

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“…More consistent findings have been reported by investigators that used the approach of increasing APN levels, either through exogenous administration or APN overexpressing mice. Although only few studies employed this strategy to study immune/inflammatory diseases, with the exception of a single study, increasing APN invariably resulted in improved outcomes [71–76]. …”

Section: Effects Of Apn On Inflammation and Immunitymentioning

confidence: 99%

Adiponectin in inflammatory and immune-mediated diseases

Fantuzzi¹

2013

Cytokine

151

114

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Circulating levels of adiponectin (APN) are reduced in obesity and associated comorbidities, with inflammation playing an important role in downregulating APN production. In contrast to obesity and metabolic disease, elevated systemic and local levels of APN are present in patients with inflammatory and immune-mediated diseases, including autoimmune and pulmonary conditions, heart and kidney failure, viral hepatitis, organ transplantation and perhaps critical illness. A positive association between inflammation and APN is usually reported in inflammatory/immune pathologies, in contrast with the negative correlation typical of metabolic disease. This review discusses the role of APN in modulation of inflammation and immunity and the potential mechanisms leading to increased levels of APN in inflammatory/immune diseases, including modification of adipose tissue physiology; relative contribution of different tissues and adipose depots; hormonal, pharmacological, nutritional and life style factors; the potential contribution of the microbiota as well as the role of altered APN clearance and release from T-cadherin-associated tissue reservoirs. Potential reasons for some of the apparently contradictory findings on the role of APN as a modulator of immunity and inflammation are also discussed, including a comparison of types of recombinant APN used for in vitro studies and strain-dependent differences in the phenotype of APN KO mice.

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“…However, it should be noted that administration of exogenous adiponectin from does not protect against caerulein-induced AP in obese mice. 31 …”

Section: Discussionmentioning

confidence: 99%

Therapeutic Administration of Orlistat, Rosiglitazone, or the Chemokine Receptor Antagonist RS102895 Fails to Improve the Severity of Acute Pancreatitis in Obese Mice

Malecki¹,

Castellanos²,

Cabay³

et al. 2014

Pancreas

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Objectives Currently there is no therapy for severe acute pancreatitis except for supportive care. The lipase inhibitor orlistat, the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone, and chemokine receptor-2 antagonists attenuate the severity of acute pancreatitis in rodents if administered prior to or at the time of induction of pancreatitis. However, it is unknown whether these treatments are effective if administered therapeutically after induction of pancreatitis. Methods Male C57BL6 mice with diet-induced obesity received two injections of mrIL-12 (150 ng/mouse) and mrIL-18 (750 ng/mouse) intraperitoneally at 24 h intervals. Mice were injected 2, 24, and 48 hours after the second injection of IL-12+IL-18 with orlistat (2 mg/mouse), rosiglitazone (0.4 mg/mouse), RS102895 (0.3 mg/mouse), or vehicle (20μL DMSO and 80 μL canola oil) and euthanized after 72 hours. Results Orlistat decreased intraabdominal fat necrosis compared to vehicle (p<0.05). However, none of the drug treatments produced significant decreases in pancreatic edema, acinar necrosis, or intrapancreatic fat necrosis. Conclusions Drugs previously shown to improve the severity of acute pancreatitis when given prior to or at the time of induction of pancreatitis, failed to do so when administered therapeutically in the IL-12+IL-18 model.

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Does Adiponectin Upregulation Attenuate the Severity of Acute Pancreatitis in Obesity?

Abstract: Adiponectin upregulation modulates the pancreatic cytokine milieu but does not attenuate pancreatitis in this model of mild acute pancreatitis.

Cited by 4 publications

References 46 publications

Rosiglitazone Improves Survival and Hastens Recovery from Pancreatic Inflammation in Obese Mice

Rosiglitazone Improves Survival and Hastens Recovery from Pancreatic Inflammation in Obese Mice

Adiponectin in inflammatory and immune-mediated diseases

Therapeutic Administration of Orlistat, Rosiglitazone, or the Chemokine Receptor Antagonist RS102895 Fails to Improve the Severity of Acute Pancreatitis in Obese Mice

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