Leptin treatment ameliorates acute lung injury in rats with cerulein-induced acute pancreatitis

Gültekin, Fatma Ayça; Kerem, Mustafa; Tatlıcıoğlu, Ertan; Aricioglu, Aysel; Unsal, Cigdem; Bukan, Neslihan

doi:10.3748/wjg.v13.i21.2932

Cited by 40 publications

(30 citation statements)

References 29 publications

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“…In these studies, extreme weight loss or gain has been associated with the development of emphysema and asthma, respectively. Further experimental studies have shown that leptin, a molecule derived from adipocytes, regulates surfactant production in type II pneumocytes and protects the lung from acute injury (2,14).…”

mentioning

confidence: 99%

Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice

Summer

Little²,

Ouchi³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

120

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mentioning

confidence: 99%

Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice

Summer

Little²,

Ouchi³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

120

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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.…”

mentioning

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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“…TNF-α and IL-1β are also released from activated neutrophils following stimulation. [29,30] In our study, the TNF-α and IL-1β levels were lower in the ALA-treated pancreatitis group than the saline-treated group (p<0.01). These results suggest that ALA decreases the inflammatory response by inhibiting activation and infiltration of neutrophils, which play a role in triggering tissue damage, and that ALA protects the pancreas tissue from free oxygen radical-induced damage.…”

Section: Histologic Preparation and Analysismentioning

confidence: 45%

Beneficial effects of alpha lipoic acid on cerulein-induced experimental acute pancreatitis in rats

Bulut¹,

Özkan²,

Ekinci³

et al. 2011

Ulus Travma Acil Cerrahi Derg

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Leptin treatment ameliorates acute lung injury in rats with cerulein-induced acute pancreatitis

Abstract: Exogenous leptin attenuates inflamma-tory changes, and reduces pro-inflammatory cytokines, nitric oxide levels, and CD40 expression in cerulein-induced AP and may be protective in AP associated ALI.

Cited by 40 publications

References 29 publications

Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice

Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice

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

Beneficial effects of alpha lipoic acid on cerulein-induced experimental acute pancreatitis in rats

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