Obesity Increases the Severity of Acute Experimental Pancreatitis in the Rat

Segersvärd, R.; Sylván, M.; Herrington, Margery K.; Larsson, J.; Permert, J.

doi:10.1080/003655201750163213

Cited by 37 publications

(29 citation statements)

References 25 publications

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“…Obesity was recently proposed as a risk factor for acute pancreatitis [16]. Furthermore, several studies have shown that obesity is strongly associated with the onset of complications and increased mortality in patients with acute pancreatitis [8,18], and a decreased survival rate has been reported in genetically obese Zucker rats following induction of experimental acute pancreatitis [25]. These results suggest that obesity could accelerate pancreatitis in WBN/Kob-fatty rats.…”

Section: Discussionsupporting

confidence: 51%

The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

et al. 2010

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Abstract:Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr fa ) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob-fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis.

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Section: Discussionsupporting

confidence: 51%

The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

et al. 2010

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“…Two meta-analyses [12,13] have indicated that obesity has relationships with the local complication rate, organ failure, and mortality. Moreover, in an animal study, obese rats were susceptible to severe pancreatitis [14]. Despite the many reports that relate obesity and severe pancreatitis, it is unclear why obese patients tend to get a more severe form of acute pancreatitis.…”

Section: Introductionmentioning

confidence: 98%

A large volume of visceral adipose tissue leads to severe acute pancreatitis

et al. 2011

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“…In patients with AP, a correlation between serum leptin and disease severity has been reported by some investigators but not by others (11,12). Although in animal models administration of leptin decreases AP severity (13)(14)(15)(16), more severe disease is present in leptin-deficient ob/ob and leptin receptordeficient db/db mice as well as leptin-receptor mutant fa/fa rats (17,18). However, the differential effect of obesity versus leptin deficiency has not been fully investigated.…”

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confidence: 99%

Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice

Sennello¹,

Fayad²,

Pini³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Obesity is associated with increased severity of acute pancreatitis (AP). The cytokines IL-18 and IL-12 are elevated in patients with AP, and IL-18 levels are high in obesity. We aimed to develop a pathologically relevant model to study obesity-associated severe AP. Lean WT and obese leptin-deficient ob/ob mice received two injections of IL-12 plus IL-18. Survival, pancreatic inflammation, and biochemical markers of AP were measured. Dosing with IL-12 plus IL-18 induced 100% lethality in ob/ob mice; no lethality was observed in WT mice. Disruption of pancreatic exocrine tissue and acinar cell death as well as serum amylase and lipase levels were significantly higher in ob/ob than in WT mice. Edematous AP developed in WT mice, whereas obese ob/ob mice developed necrotizing AP. Adipose tissue necrosis and saponification were present in cytokine-injected ob/ob but not in WT mice. Severe hypocalcemia and elevated acute-phase response developed in ob/ob mice. The cytokine combination induced high levels of regenerating protein 1 and pancreatitis-associated protein expression in the pancreas of WT but not of ob/ob mice. To differentiate the contribution of obesity to that of leptin deficiency, mice received short-and long-term leptin replacement therapy. Shortterm leptin reconstitution in the absence of major weight loss did not protect ob/ob mice, whereas leptin deficiency in the absence of obesity resulted in a significant reduction in the severity of the pancreatitis. In conclusion, we developed a pathologically relevant model of AP in which obesity per se is associated with increased severity.cytokines ͉ inflammation ͉ obesity ͉ pancreas A cute pancreatitis (AP) is an inflammatory disorder that ranges from interstitial edema to confluent necrosis and hemorrhage. In severe cases, progress to circulatory shock, acute lung injury, renal failure, and eventual death may occur (1). Despite some controversy, numerous studies have demonstrated that obesity is associated with increased risk of the severe form of AP and with development of life-threatening complications (2-8). However, the mechanism by which increased adiposity worsens AP remains unknown.Leptin, a protein mainly produced by adipocytes, is a critical regulator of appetite (9). Leptin exerts important regulatory effects on inflammation (10). In the context of AP, the role of leptin remains controversial. In patients with AP, a correlation between serum leptin and disease severity has been reported by some investigators but not by others (11,12). Although in animal models administration of leptin decreases AP severity (13-16), more severe disease is present in leptin-deficient ob/ob and leptin receptordeficient db/db mice as well as leptin-receptor mutant fa/fa rats (17, 18). However, the differential effect of obesity versus leptin deficiency has not been fully investigated.IL-12 and IL-18 are two proinflammatory cytokines that drive the Th1 cell response, characterized by high levels of IFN-␥ (19). Both cytokines are mainly produced by monocytes/macrophages....

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Obesity Increases the Severity of Acute Experimental Pancreatitis in the Rat

Abstract: Obesity had a negative influence on the outcome of necrotizing pancreatitis that was related to the magnitude of the pancreatic insult. The sodium taurocholate model in obese rats would be useful for future mechanistic studies of the effect of obesity on pancreatitis.

Cited by 37 publications

References 25 publications

The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

A large volume of visceral adipose tissue leads to severe acute pancreatitis

Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice

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