Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice

B. Navia, B. Ferrer, M. Giralt, G. Comes, J. Carrasco, A. Molinero, A. Quintana, J. Leclerc, B. Viollet, R. M. Señarís, J. Hidalgo

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aim: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, but because many types of cells can synthesize and respond to IL-6 considerable uncertainty still exists about the mechanisms underlying IL-6 effects. Therefore, the aim of this study was to analyse the effects of tissue-specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre inducible system (aP2-Cre-ERT2). Methods: Tissue-specific IL-6 KO mice (aP2-IL-6 KO mice) were produced upon tamoxifen administration and were fed a high-fat diet (HFD, 58.4% kcal from fat) or a control diet (18%) for 14 weeks. Results: aP2-IL-6 KO female mice on a HFD gained less weight and adiposity than littermate wild-type mice, but these effects were not observed in males. Hypothalamic factors such as NPY and AgRP showed a pattern of expression consistent with this sex-specific phenotype. PGC-1α expression was increased in several tissues in aP2-IL-6 KO female mice, which is compatible with increased energy expenditure. Serum leptin, insulin, glucose, cholesterol and triglycerides levels were increased by HFD, and in females IL-6 deficiency reversed this effect in the case of insulin and cholesterol. HFD induced impaired responses to insulin and glucose tolerance tests, but no significant differences between genotypes were observed. Conclusion: The present results demonstrate that deletion of IL-6 driven by aP2-Cre regulates body weight, body fat and metabolism in a sex-specific fashion.

Original languageEnglish (US)
Pages (from-to)585-596
Number of pages12
JournalActa Physiologica
Volume211
Issue number4
DOIs
StatePublished - Aug 2014
Externally publishedYes

Fingerprint

Adiposity
High Fat Diet
Weight Gain
Interleukin-6
Insulin
Cholesterol
Body Weight
Fatty Acid-Binding Proteins
Tamoxifen
Glucose Tolerance Test
Leptin
Energy Metabolism
Uncertainty
Adipose Tissue
Triglycerides
Fats
Genotype
Cytokines
Diet
Phenotype

Keywords

  • AP2-Cre-induced IL-6 deficiency
  • Body weight
  • High-fat diet
  • Hypothalamic factors
  • Insulin signalling

ASJC Scopus subject areas

  • Physiology

Cite this

Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice. / Navia, B.; Ferrer, B.; Giralt, M.; Comes, G.; Carrasco, J.; Molinero, A.; Quintana, A.; Leclerc, J.; Viollet, B.; Señarís, R. M.; Hidalgo, J.

In: Acta Physiologica, Vol. 211, No. 4, 08.2014, p. 585-596.

Research output: Contribution to journalArticle

Navia, B, Ferrer, B, Giralt, M, Comes, G, Carrasco, J, Molinero, A, Quintana, A, Leclerc, J, Viollet, B, Señarís, RM & Hidalgo, J 2014, 'Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice', Acta Physiologica, vol. 211, no. 4, pp. 585-596. https://doi.org/10.1111/apha.12328
Navia, B. ; Ferrer, B. ; Giralt, M. ; Comes, G. ; Carrasco, J. ; Molinero, A. ; Quintana, A. ; Leclerc, J. ; Viollet, B. ; Señarís, R. M. ; Hidalgo, J. / Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice. In: Acta Physiologica. 2014 ; Vol. 211, No. 4. pp. 585-596.
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abstract = "Aim: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, but because many types of cells can synthesize and respond to IL-6 considerable uncertainty still exists about the mechanisms underlying IL-6 effects. Therefore, the aim of this study was to analyse the effects of tissue-specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre inducible system (aP2-Cre-ERT2). Methods: Tissue-specific IL-6 KO mice (aP2-IL-6 KO mice) were produced upon tamoxifen administration and were fed a high-fat diet (HFD, 58.4{\%} kcal from fat) or a control diet (18{\%}) for 14 weeks. Results: aP2-IL-6 KO female mice on a HFD gained less weight and adiposity than littermate wild-type mice, but these effects were not observed in males. Hypothalamic factors such as NPY and AgRP showed a pattern of expression consistent with this sex-specific phenotype. PGC-1α expression was increased in several tissues in aP2-IL-6 KO female mice, which is compatible with increased energy expenditure. Serum leptin, insulin, glucose, cholesterol and triglycerides levels were increased by HFD, and in females IL-6 deficiency reversed this effect in the case of insulin and cholesterol. HFD induced impaired responses to insulin and glucose tolerance tests, but no significant differences between genotypes were observed. Conclusion: The present results demonstrate that deletion of IL-6 driven by aP2-Cre regulates body weight, body fat and metabolism in a sex-specific fashion.",
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T1 - Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice

AU - Navia, B.

AU - Ferrer, B.

AU - Giralt, M.

AU - Comes, G.

AU - Carrasco, J.

AU - Molinero, A.

AU - Quintana, A.

AU - Leclerc, J.

AU - Viollet, B.

AU - Señarís, R. M.

AU - Hidalgo, J.

PY - 2014/8

Y1 - 2014/8

N2 - Aim: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, but because many types of cells can synthesize and respond to IL-6 considerable uncertainty still exists about the mechanisms underlying IL-6 effects. Therefore, the aim of this study was to analyse the effects of tissue-specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre inducible system (aP2-Cre-ERT2). Methods: Tissue-specific IL-6 KO mice (aP2-IL-6 KO mice) were produced upon tamoxifen administration and were fed a high-fat diet (HFD, 58.4% kcal from fat) or a control diet (18%) for 14 weeks. Results: aP2-IL-6 KO female mice on a HFD gained less weight and adiposity than littermate wild-type mice, but these effects were not observed in males. Hypothalamic factors such as NPY and AgRP showed a pattern of expression consistent with this sex-specific phenotype. PGC-1α expression was increased in several tissues in aP2-IL-6 KO female mice, which is compatible with increased energy expenditure. Serum leptin, insulin, glucose, cholesterol and triglycerides levels were increased by HFD, and in females IL-6 deficiency reversed this effect in the case of insulin and cholesterol. HFD induced impaired responses to insulin and glucose tolerance tests, but no significant differences between genotypes were observed. Conclusion: The present results demonstrate that deletion of IL-6 driven by aP2-Cre regulates body weight, body fat and metabolism in a sex-specific fashion.

AB - Aim: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, but because many types of cells can synthesize and respond to IL-6 considerable uncertainty still exists about the mechanisms underlying IL-6 effects. Therefore, the aim of this study was to analyse the effects of tissue-specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre inducible system (aP2-Cre-ERT2). Methods: Tissue-specific IL-6 KO mice (aP2-IL-6 KO mice) were produced upon tamoxifen administration and were fed a high-fat diet (HFD, 58.4% kcal from fat) or a control diet (18%) for 14 weeks. Results: aP2-IL-6 KO female mice on a HFD gained less weight and adiposity than littermate wild-type mice, but these effects were not observed in males. Hypothalamic factors such as NPY and AgRP showed a pattern of expression consistent with this sex-specific phenotype. PGC-1α expression was increased in several tissues in aP2-IL-6 KO female mice, which is compatible with increased energy expenditure. Serum leptin, insulin, glucose, cholesterol and triglycerides levels were increased by HFD, and in females IL-6 deficiency reversed this effect in the case of insulin and cholesterol. HFD induced impaired responses to insulin and glucose tolerance tests, but no significant differences between genotypes were observed. Conclusion: The present results demonstrate that deletion of IL-6 driven by aP2-Cre regulates body weight, body fat and metabolism in a sex-specific fashion.

KW - AP2-Cre-induced IL-6 deficiency

KW - Body weight

KW - High-fat diet

KW - Hypothalamic factors

KW - Insulin signalling

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