General Information:

Id: 1,655 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Obesity - [OMIM]
Mus musculus
male
article
Reference: El-Haschimi K et al.(2000) Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity J. Clin. Invest. 105: 1827-1832 [PMID: 10862798]

Interaction Information:

Comment High-fat feeding and attendant obesity were associated with increased leptin levels.
Formal Description
Interaction-ID: 12127

environment

high-fat diet

increases_quantity of

gene/protein

LEP

Comment In mice fed the low-fat diet, leptin activated STAT3 (signal transducer and activator of transcription) signaling when administered via the intraperitoneal (ip) or the intracerebroventricular (icv) route, with the half-maximal dose being 30-fold less when given by the icv route.
Formal Description
Interaction-ID: 12128

gene/protein

LEP

increases_activity of

process

STAT3 signaling pathway

after low-fat diet
Comment After 4 weeks on the diet, hypothalamic STAT3 signaling after ip leptin administration was equivalent in both diet groups. In contrast, peripherally administered leptin was completely unable to activate hypothalamic STAT3 signaling, as measured by gel shift assay after 15 weeks of high-fat diet. Despite the absence of detectable signaling after peripheral leptin at 15 weeks, the mice fed the high-fat diet retained the capacity to respond to icv leptin, although the magnitude of STAT3 activation was substantially reduced. These results suggest that leptin resistance induced by a high-fat diet evolves during the course of the diet and has at least two independent causes: an apparent defect in access to sites of action in the hypothalamus that markedly limits the ability of peripheral leptin to activate hypothalamic STAT signaling, and an intracellular signaling defect in leptin-responsive hypothalamic neurons that lies upstream of STAT3 activation.
Formal Description
Interaction-ID: 12130

environment

high-fat diet

decreases transport of

gene/protein

LEP

into brain