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Cell Metab. 2015 Jun 2;21(6):877-82. doi: 10.1016/j.cmet.2015.04.015. Epub 2015 May 14.

Diet-induced obese mice retain endogenous leptin action.

Author information

1
Department of Internal Medicine, Metabolic Diseases Institute, University of Cincinnati, OH 45237, USA.
2
Department of Internal Medicine, Metabolic Diseases Institute, University of Cincinnati, OH 45237, USA; Department of Pharmacology, University of Granada, Granada 18071, Spain.
3
Institute of Biochemistry, Food Science, and Nutrition, The Hebrew University of Jerusalem, Rehovot 7610001, Israel.
4
Department of Internal Medicine, Metabolic Diseases Institute, University of Cincinnati, OH 45237, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
5
Department of Internal Medicine, Metabolic Diseases Institute, University of Cincinnati, OH 45237, USA. Electronic address: pereztdo@ucmail.uc.edu.

Abstract

Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice.

Comment in

PMID:
25980347
PMCID:
PMC4456263
DOI:
10.1016/j.cmet.2015.04.015
[Indexed for MEDLINE]
Free PMC Article

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