Female Nur77-deficient mice show increased susceptibility to diet-induced obesity

PLoS One. 2013;8(1):e53836. doi: 10.1371/journal.pone.0053836. Epub 2013 Jan 14.

Abstract

Adipose tissue is essential in the regulation of body weight. The key process in fat catabolism and the provision of energy substrate during times of nutrient deprivation or enhanced energy demand is the hydrolysis of triglycerides and the release of fatty acids and glycerol. Nur77 is a member of the NR4A subfamily of nuclear receptors that plays an important metabolic role, modulating hepatic glucose metabolism and lipolysis in muscle. However, its endogenous role on white adipose tissue, as well as the gender dependency of these mechanisms, remains largely unknown. Male and female wild type and Nur77 deficient mice were fed with a high fat diet (45% calories from fat) for 4 months. Mice were analyzed in vivo with the indirect calorimetry system, and tissues were analyzed by real-time PCR and Western blot analysis. Female, but not male Nur77 deficient mice, gained more weight and fat mass when compared to wild type mice fed with high fat diet, which can be explained by decreased energy expenditure. The lack of Nur77 also led to a decreased pHSL/HSL ratio in white adipose tissue and increased expression of CIDEA in brown adipose tissue of female Nur77 deficient mice. Overall, these findings suggest that Nur77 is an important physiological modulator of lipid metabolism in adipose tissue and that there are gender differences in the sensitivity to deletion of the Nur77 signaling. The decreased energy expenditure and the actions of Nur77 on liver, muscle, brown and white adipose tissue contribute to the increased susceptibility to diet-induced obesity in females lacking Nur77.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / metabolism
  • Adipose Tissue, White / pathology
  • Adiposity
  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Blood Glucose / metabolism
  • Body Weight
  • Cholesterol / blood
  • Diet, High-Fat / adverse effects*
  • Disease Susceptibility
  • Energy Metabolism
  • Fatty Acids, Nonesterified / blood
  • Female
  • Gene Knockout Techniques
  • Homeostasis
  • Insulin / blood
  • Leptin / blood
  • Lipolysis
  • Liver / metabolism
  • Male
  • Mice
  • Muscles / metabolism
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / deficiency*
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Obesity / etiology*
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Signal Transduction
  • Triglycerides / blood

Substances

  • Apoptosis Regulatory Proteins
  • Blood Glucose
  • Cidea protein, mouse
  • Fatty Acids, Nonesterified
  • Insulin
  • Leptin
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Triglycerides
  • Cholesterol

Grant support

This work has been supported by grants from Ministerio de Ciencia e Innovación (to RN: RYC-2008-02219; to RN: SAF2009-07049; to ML: RyC-2007-00211; to CD: BFU2008-02001), Xunta de Galicia (to ML: 10PXIB208164PR and to RN: 2010/14); Fondo Investigationes Sanitarias (to ML: PS09/01880), European Union leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 245009 and also ERC-2011-StG-OBESITY53-281408 (to RN). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.