Diet-induced obese mice retain endogenous leptin action

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Weight / genetics
  • Diet / adverse effects*
  • Hyperlipidemias / chemically induced
  • Hyperlipidemias / genetics
  • Hyperlipidemias / metabolism
  • Leptin / genetics
  • Leptin / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • Obesity / chemically induced
  • Obesity / genetics
  • Obesity / metabolism*
  • Receptor, Melanocortin, Type 4 / genetics
  • Receptor, Melanocortin, Type 4 / metabolism
  • Receptors, Leptin / antagonists & inhibitors
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism

Substances

  • Leptin
  • MC4R protein, mouse
  • Receptor, Melanocortin, Type 4
  • Receptors, Leptin
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins