Leptin and Wound Inflammation in Diabetic ob/ob Mice

Goren, Itamar; Kämpfer, Heiko; Podda, Maurizio; Pfeilschifter, Josef; Frank, Stefan

doi:10.2337/diabetes.52.11.2821

Cited by 95Wound Healing and TreatmentsAdipokines, Inflammation, and Metabolic DiseasesSkin Diseases and Diabetes

Leptin and Wound Inflammation in Diabetic ob/ob Mice

Goren, Itamar, Kämpfer, Heiko, Podda, Maurizio, Pfeilschifter, Josef, Frank, Stefan·2003·Diabetes

DOI 10.2337/diabetes.52.11.2821

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Abstract

In this study, we investigated the role of leptin for the inflammatory response in diabetes-impaired skin repair. We demonstrated, that systemic treatment of diabetic ob/ob mice with leptin blunted polymorphonuclear neutrophil (PMN), but not macrophage influx into the wound site. Closed wounds of leptin-administered mice were characterized by tremendous numbers of macrophage within the granulation tissue. In line, leptin supplementation potently attenuated epithelium-derived CXC- but not CC-chemokine expression. PMNs were preferentially located in the scab, but macrophages predominantly resided within the wound stroma of the animals. The scabs of nonhealing wounds were most likely to serve as sinks for bioactive inflammatory mediators, which were still capable to drive gene expression in keratinocytes in vitro. Differential effects of leptin on PMN and macrophage axes of inflammation must be indirect, as topical administration of leptin onto wounds of ob/ob mice did not reduce PMN influx into the wounded areas. Moreover, caloric-restricted, pair-fed ob/ob mice were characterized by impaired healing conditions that were associated with persisting PMNs. Interestingly, we documented the absence of leptin receptor expression in human diabetic foot ulcers. Thus, we show that leptin might function as a regulatory link between the endocrine and the immune system in the context of skin repair.

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Elevated levels of IL-1β have been found in wounds of diabetic humans and mice.
“Elevated levels of IL-1β have been found in wounds of diabetic humans and mice (12,15,19,20)”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [12]
During impaired healing associated with diabetes, wounds exhibit prolonged accumulation of Mp associated with elevated levels of proinflammatory cytokines and proteases and reduced levels of various growth factors.
“During impaired healing associated with diabetes, wounds exhibit prolonged accumulation of Mp associated with elevated levels of proinflammatory cytokines and proteases and reduced levels of various growth factors (2,12,13).”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [12]

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Authors: Goren, I., Kämpfer, H., Podda, M., Pfeilschifter, J., & Frank, S.
Affiliations: Goethe University Frankfurt (DE)
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
ORCID: Goren, Itamar
Podda, Maurizio
Pfeilschifter, Josef
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2003-11-01
Volume: 52
Issue: 11
Pages: 2821-2832
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.52.11.2821
OpenAlex: W2142460886
Cited by: 95
References: 41
Citations by year: 2025: 2 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 10 · 2012: 6
FWCI: 5.60
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Dermatology › Skin Diseases and Diabetes
Keywords: leptin, wound inflammation, ob/ob mice, neutrophils, macrophages, CXC chemokines, CC chemokines, keratinocytes, diabetic foot ulcer, leptin receptor, caloric restriction
MeSH terms: Administration, Topical, Animals, Blood Glucose, Diabetes Mellitus, Diabetes Mellitus, Type 2, Disease Models, Animal, Female, Gene Expression Regulation, Inflammation, Macrophages, Mice, Inbred C57BL, Mice, Obese, Neutrophils, Obesity, Recombinant Proteins, RNA, Messenger, Transcription, Genetic, Wound Healing, Chemokines, Leptin, Mice

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Leptin and Wound Inflammation in Diabetic ob/ob Mice

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