Leptin: a pivotal mediator of intestinal inflammation in mice

Gastroenterology. 2002 Jun;122(7):2011-25. doi: 10.1053/gast.2002.33631.


Background & aims: In addition to acting as a regulator of food intake and energy expenditure, leptin can also modulate immune and inflammatory responses. The role of leptin in intestinal inflammation is the focus of the present study.

Methods: Acute and chronic colitis were induced in leptin-deficient ob/ob or wild-type (WT) mice using dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS). The severity of colitis was evaluated, and possible mechanisms were studied.

Results: Leptin directly stimulates intraepithelial lymphocytes (IELs) and lamina propria mononuclear cells (LPMCs). In the DSS acute model, ob/ob mice exhibited a 72% reduction of colitis severity and spontaneous release of proinflammatory cytokines from the colon compared with WT mice. Replacement of leptin in ob/ob mice converted disease resistance to susceptibility, indicating that leptin deficiency, not obesity, accounts for the resistance to acute DSS-induced colitis. During chronic DSS-induced colitis and TNBS-induced colitis, in addition to reduced disease severity, ob/ob mice exhibited a significant attenuation in intestinal inflammation, accompanied by reduced production of cytokines and chemokines. When compared with WT mice, CD8(+) IELs of ob/ob mice were reduced in number as well as in their ability to synthesize interferon gamma. In addition, LPMCs of ob/ob mice showed increased apoptosis in untreated as well as DSS- or TNBS-treated mice. Phosphorylation of signal transducer and activator of transcription 3 and induction of cyclooxygenase 2 were absent in the colon of DSS-fed ob/ob mice.

Conclusions: These results show that leptin represents a functional link between the endocrine and immune systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokines / metabolism
  • Chronic Disease
  • Colitis / chemically induced
  • Colitis / complications
  • Colitis / pathology
  • Colitis / physiopathology*
  • Colon / metabolism
  • Cyclooxygenase 2
  • Cytokines / biosynthesis
  • Cytokines / metabolism
  • DNA-Binding Proteins / physiology
  • Dextran Sulfate
  • Disease Susceptibility
  • Enzyme Induction
  • Female
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Isoenzymes / metabolism
  • Leptin / deficiency
  • Leptin / pharmacology
  • Leptin / physiology*
  • Lymphocytes / drug effects
  • Mice
  • Mice, Inbred C57BL / genetics
  • Monocytes / drug effects
  • Monocytes / physiology
  • Obesity / complications
  • Obesity / genetics
  • Obesity / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Reference Values
  • STAT3 Transcription Factor
  • Trans-Activators / physiology
  • Trinitrobenzenesulfonic Acid


  • Chemokines
  • Cytokines
  • DNA-Binding Proteins
  • Isoenzymes
  • Leptin
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Trinitrobenzenesulfonic Acid
  • Dextran Sulfate
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases