Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy

Shangang Zhao; Yi Zhu; Robbie D Schultz; Na Li; Zhenyan He; Zhuzhen Zhang; Alexandre Caron; Qingzhang Zhu; Kai Sun; Wei Xiong; Hui Deng; Jia Sun; Yingfeng Deng; Min Kim; Charlotte E Lee; Ruth Gordillo; Tiemin Liu; Angela K Odle; Gwen V Childs; Ningyan Zhang; Christine M Kusminski; Joel K Elmquist; Kevin W Williams; Zhiqiang An; Philipp E Scherer

doi:10.1016/j.cmet.2019.08.005

Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy

Shangang Zhao, Yi Zhu, Robbie D Schultz, Na Li, Zhenyan He, Zhuzhen Zhang, Alexandre Caron, Qingzhang Zhu, Kai Sun, Wei Xiong, Hui Deng, Jia Sun, Yingfeng Deng, Min Kim, Charlotte E Lee, Ruth Gordillo, Tiemin Liu, Angela K Odle, Gwen V Childs, Ningyan ZhangChristine M Kusminski, Joel K Elmquist, Kevin W Williams, Zhiqiang An, Philipp E Scherer

Internal Medicine

Research output: Contribution to journal › Article › peer-review

200 Scopus citations

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.

Original language	English
Pages (from-to)	706-719.e6
Journal	Cell Metabolism
Volume	30
Issue number	4
DOIs	https://doi.org/10.1016/j.cmet.2019.08.005
State	Published - Oct 1 2019

Bibliographical note

Keywords

Animals
Antibodies, Neutralizing/pharmacology
Eating/drug effects
Energy Metabolism/drug effects
Insulin/metabolism
Insulin Resistance
Leptin/antagonists & inhibitors
Mice
Mice, Inbred Strains
Obesity/metabolism
Weight Loss/drug effects
Weight Reduction Programs/methods

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cmet.2019.08.005

Cite this

Zhao, S., Zhu, Y., Schultz, R. D., Li, N., He, Z., Zhang, Z., Caron, A., Zhu, Q., Sun, K., Xiong, W., Deng, H., Sun, J., Deng, Y., Kim, M., Lee, C. E., Gordillo, R., Liu, T., Odle, A. K., Childs, G. V., ... Scherer, P. E. (2019). Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy. Cell Metabolism, 30(4), 706-719.e6. https://doi.org/10.1016/j.cmet.2019.08.005

@article{f0057afc441847f2a95f3fbca0964e1e,

title = "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.",

keywords = "Animals, Antibodies, Neutralizing/pharmacology, Eating/drug effects, Energy Metabolism/drug effects, Insulin/metabolism, Insulin Resistance, Leptin/antagonists & inhibitors, Mice, Mice, Inbred Strains, Obesity/metabolism, Weight Loss/drug effects, Weight Reduction Programs/methods",

author = "Shangang Zhao and Yi Zhu and Schultz, {Robbie D} and Na Li and Zhenyan He and Zhuzhen Zhang and Alexandre Caron and Qingzhang Zhu and Kai Sun and Wei Xiong and Hui Deng and Jia Sun and Yingfeng Deng and Min Kim and Lee, {Charlotte E} and Ruth Gordillo and Tiemin Liu and Odle, {Angela K} and Childs, {Gwen V} and Ningyan Zhang and Kusminski, {Christine M} and Elmquist, {Joel K} and Williams, {Kevin W} and Zhiqiang An and Scherer, {Philipp E}",

year = "2019",

month = oct,

day = "1",

doi = "10.1016/j.cmet.2019.08.005",

language = "English",

volume = "30",

pages = "706--719.e6",

number = "4",

}

Zhao, S, Zhu, Y, Schultz, RD, Li, N, He, Z, Zhang, Z, Caron, A, Zhu, Q, Sun, K, Xiong, W, Deng, H, Sun, J, Deng, Y, Kim, M, Lee, CE, Gordillo, R, Liu, T, Odle, AK, Childs, GV, Zhang, N, Kusminski, CM, Elmquist, JK, Williams, KW, An, Z & Scherer, PE 2019, 'Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy', Cell Metabolism, vol. 30, no. 4, pp. 706-719.e6. https://doi.org/10.1016/j.cmet.2019.08.005

TY - JOUR

T1 - Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy

AU - Zhao, Shangang

AU - Zhu, Yi

AU - Schultz, Robbie D

AU - Li, Na

AU - He, Zhenyan

AU - Zhang, Zhuzhen

AU - Caron, Alexandre

AU - Zhu, Qingzhang

AU - Sun, Kai

AU - Xiong, Wei

AU - Deng, Hui

AU - Sun, Jia

AU - Deng, Yingfeng

AU - Kim, Min

AU - Lee, Charlotte E

AU - Gordillo, Ruth

AU - Liu, Tiemin

AU - Odle, Angela K

AU - Childs, Gwen V

AU - Zhang, Ningyan

AU - Kusminski, Christine M

AU - Elmquist, Joel K

AU - Williams, Kevin W

AU - An, Zhiqiang

AU - Scherer, Philipp E

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antibodies, Neutralizing/pharmacology

KW - Eating/drug effects

KW - Energy Metabolism/drug effects

KW - Insulin/metabolism

KW - Insulin Resistance

KW - Leptin/antagonists & inhibitors

KW - Mice

KW - Mice, Inbred Strains

KW - Obesity/metabolism

KW - Weight Loss/drug effects

KW - Weight Reduction Programs/methods

U2 - 10.1016/j.cmet.2019.08.005

DO - 10.1016/j.cmet.2019.08.005

M3 - Article

C2 - 31495688

SN - 1550-4131

VL - 30

SP - 706-719.e6

JO - Cell Metabolism

JF - Cell Metabolism

IS - 4

ER -

Partial Leptin Reduction as an Insulin Sensitization and Weight Loss Strategy

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this