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Leptin replacement reestablishes brain insulin action in the hypothalamus in congenital leptin deficiency.

Diabetes Care 41, 907-910 (2018)
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OBJECTIVEHuman obesity is associated with impaired central insulin signaling, and in very rare cases, severe obesity can be caused by congenital leptin deficiency. In such patients, leptin replacement results in substantial weight loss and improvement in peripheral metabolism.RESEARCH DESIGN AND METHODSIn a leptin-deficient patient, we investigated the impact of leptin substitution on central insulin action, as quantified by changes in neuronal activity after intranasal insulin application. This was assessed before and during the first year of metreleptin substitution.RESULTSAfter only 1 year, treatment with metreleptin reestablishes brain insulin sensitivity, particularly in the hypothalamus and, to a lesser degree, in the prefrontal cortex. Results are depicted in comparison with a control group. In our patient, brain activation changes were accompanied by substantial weight loss, reduced visceral adipose tissue, reduced intrahepatic lipid content, and improved whole-body insulin sensitivity.CONCLUSIONSLeptin replacement and weight loss improved homeostatic insulin action in the patient in question.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Selective Insulin; Resistance; Humans; Overweight; Disorders; Adults; Areas
Reviewing status