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Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy.


ABSTRACT: The physiological role of leptin is thought to be a driving force to reduce food intake and increase energy expenditure. However, leptin therapies in the clinic have failed to effectively treat obesity, predominantly due to a phenomenon referred to as leptin resistance. The mechanisms linking obesity and the associated leptin resistance remain largely unclear. With various mouse models and a leptin neutralizing antibody, we demonstrated that hyperleptinemia is a driving force for metabolic disorders. A partial reduction of plasma leptin levels in the context of obesity restores hypothalamic leptin sensitivity and effectively reduces weight gain and enhances insulin sensitivity. These results highlight that a partial reduction in plasma leptin levels leads to improved leptin sensitivity, while pointing to a new avenue for therapeutic interventions in the treatment of obesity and its associated comorbidities.

SUBMITTER: Zhao S 

PROVIDER: S-EPMC6774814 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The physiological role of leptin is thought to be a driving force to reduce food intake and increase energy expenditure. However, leptin therapies in the clinic have failed to effectively treat obesity, predominantly due to a phenomenon referred to as leptin resistance. The mechanisms linking obesity and the associated leptin resistance remain largely unclear. With various mouse models and a leptin neutralizing antibody, we demonstrated that hyperleptinemia is a driving force for metabolic disor  ...[more]

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