Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet.

Francesca Rappa, Francesco Cappello, Valerio Pazienza, Sheedfar, Hofker, Vermeer, Van Der Molen, Villarroya, Hofker, Koonen, Manlio Vinciguerra, Gianluigi Mazzoccoli, Hofker, Cappello, Francesc Villarroya

Risultato della ricerca: Article

15 Citazioni (Scopus)

Abstract

AbstractBackground/objectives:In the context of obesity, epigenetic mechanisms regulate cell-specific chromatin plasticity, perpetuating gene expression responses to nutrient excess. MacroH2A1, a variant of histone H2A, emerged as a key chromatin regulator sensing small nutrients during cell proliferation and differentiation. Mice genetically ablated for macroH2A1 (knockout (KO)) do not show overt phenotypes under a standard diet. Our objective was to analyse the in vivo role of macroH2A1 in response to nutritional excess.Methods:Twelve-week-old whole-body macroH2A1 KO male mice were given a high-fat diet (60% energy from lard) for 12 weeks until being killed, and examined for glucose and insulin tolerance, and for body fat composition. Energy expenditure was assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in the brown adipose tissue (BAT) or in adipogenesis in the visceral adipose tissue (VAT).Results:Under a chow diet, macroH2A1 KO mice did not differ from their wild-type (WT) littermates for body weight, and for sensitivity to glucose or insulin. However, KO mice displayed decreased heat production (P<0.05), and enhanced total activity during the night (P<0.01). These activities related to protection against diet-induced obesity in KO mice, which displayed decreased body weight owing to a specific decrease in fat mass (P<0.05), increased tolerance to glucose (P<0.05), and enhanced total activity during the day (P<0.05), compared with WT mice. KO mice displayed increased expression of thermogenic genes (Ucp1, P<0.05; Glut4, P<0.05; Cox4, P<0.01) in BAT and a decreased expression of adipogenic genes (Pparγ, P<0.05; Fabp4, P<0.05; Glut4, P<0.05) in VAT compared with WT mice, indicative of augmented energy expenditure.Conclusions:Genetic eviction of macroH2A1 confers protection against diet-induced obesity and metabolic derangements in mice. Inhibition of macroH2A1 might be a helpful strategy for epigenetic therapy of obesity.
Lingua originaleEnglish
pagine (da-a)331-338
Numero di pagine8
RivistaInternational Journal of Obesity
Volume39
Stato di pubblicazionePublished - 2014

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Thinness
High Fat Diet
Knockout Mice
Energy Metabolism
Glucose
Obesity
Diet
Gene Expression
Brown Adipose Tissue
Intra-Abdominal Fat
Thermogenesis
Epigenomics
Chromatin
Body Weight
Insulin
Food
Adipogenesis
Body Composition
Histones
Adipose Tissue

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cita questo

Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet. / Rappa, Francesca; Cappello, Francesco; Pazienza, Valerio; Sheedfar; Hofker; Vermeer; Van Der Molen; Villarroya; Hofker; Koonen; Vinciguerra, Manlio; Mazzoccoli, Gianluigi; Hofker; Cappello; Villarroya, Francesc.

In: International Journal of Obesity, Vol. 39, 2014, pag. 331-338.

Risultato della ricerca: Article

Rappa, F, Cappello, F, Pazienza, V, Sheedfar, Hofker, Vermeer, Van Der Molen, Villarroya, Hofker, Koonen, Vinciguerra, M, Mazzoccoli, G, Hofker, Cappello & Villarroya, F 2014, 'Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet.', International Journal of Obesity, vol. 39, pagg. 331-338.
Rappa, Francesca ; Cappello, Francesco ; Pazienza, Valerio ; Sheedfar ; Hofker ; Vermeer ; Van Der Molen ; Villarroya ; Hofker ; Koonen ; Vinciguerra, Manlio ; Mazzoccoli, Gianluigi ; Hofker ; Cappello ; Villarroya, Francesc. / Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet. In: International Journal of Obesity. 2014 ; Vol. 39. pagg. 331-338.
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title = "Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet.",
abstract = "AbstractBackground/objectives:In the context of obesity, epigenetic mechanisms regulate cell-specific chromatin plasticity, perpetuating gene expression responses to nutrient excess. MacroH2A1, a variant of histone H2A, emerged as a key chromatin regulator sensing small nutrients during cell proliferation and differentiation. Mice genetically ablated for macroH2A1 (knockout (KO)) do not show overt phenotypes under a standard diet. Our objective was to analyse the in vivo role of macroH2A1 in response to nutritional excess.Methods:Twelve-week-old whole-body macroH2A1 KO male mice were given a high-fat diet (60{\%} energy from lard) for 12 weeks until being killed, and examined for glucose and insulin tolerance, and for body fat composition. Energy expenditure was assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in the brown adipose tissue (BAT) or in adipogenesis in the visceral adipose tissue (VAT).Results:Under a chow diet, macroH2A1 KO mice did not differ from their wild-type (WT) littermates for body weight, and for sensitivity to glucose or insulin. However, KO mice displayed decreased heat production (P<0.05), and enhanced total activity during the night (P<0.01). These activities related to protection against diet-induced obesity in KO mice, which displayed decreased body weight owing to a specific decrease in fat mass (P<0.05), increased tolerance to glucose (P<0.05), and enhanced total activity during the day (P<0.05), compared with WT mice. KO mice displayed increased expression of thermogenic genes (Ucp1, P<0.05; Glut4, P<0.05; Cox4, P<0.01) in BAT and a decreased expression of adipogenic genes (Pparγ, P<0.05; Fabp4, P<0.05; Glut4, P<0.05) in VAT compared with WT mice, indicative of augmented energy expenditure.Conclusions:Genetic eviction of macroH2A1 confers protection against diet-induced obesity and metabolic derangements in mice. Inhibition of macroH2A1 might be a helpful strategy for epigenetic therapy of obesity.",
author = "Francesca Rappa and Francesco Cappello and Valerio Pazienza and Sheedfar and Hofker and Vermeer and {Van Der Molen} and Villarroya and Hofker and Koonen and Manlio Vinciguerra and Gianluigi Mazzoccoli and Hofker and Cappello and Francesc Villarroya",
year = "2014",
language = "English",
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pages = "331--338",
journal = "International Journal of Obesity",
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TY - JOUR

T1 - Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet.

AU - Rappa, Francesca

AU - Cappello, Francesco

AU - Pazienza, Valerio

AU - Sheedfar, null

AU - Hofker, null

AU - Vermeer, null

AU - Van Der Molen, null

AU - Villarroya, null

AU - Hofker, null

AU - Koonen, null

AU - Vinciguerra, Manlio

AU - Mazzoccoli, Gianluigi

AU - Hofker, null

AU - Cappello, null

AU - Villarroya, Francesc

PY - 2014

Y1 - 2014

N2 - AbstractBackground/objectives:In the context of obesity, epigenetic mechanisms regulate cell-specific chromatin plasticity, perpetuating gene expression responses to nutrient excess. MacroH2A1, a variant of histone H2A, emerged as a key chromatin regulator sensing small nutrients during cell proliferation and differentiation. Mice genetically ablated for macroH2A1 (knockout (KO)) do not show overt phenotypes under a standard diet. Our objective was to analyse the in vivo role of macroH2A1 in response to nutritional excess.Methods:Twelve-week-old whole-body macroH2A1 KO male mice were given a high-fat diet (60% energy from lard) for 12 weeks until being killed, and examined for glucose and insulin tolerance, and for body fat composition. Energy expenditure was assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in the brown adipose tissue (BAT) or in adipogenesis in the visceral adipose tissue (VAT).Results:Under a chow diet, macroH2A1 KO mice did not differ from their wild-type (WT) littermates for body weight, and for sensitivity to glucose or insulin. However, KO mice displayed decreased heat production (P<0.05), and enhanced total activity during the night (P<0.01). These activities related to protection against diet-induced obesity in KO mice, which displayed decreased body weight owing to a specific decrease in fat mass (P<0.05), increased tolerance to glucose (P<0.05), and enhanced total activity during the day (P<0.05), compared with WT mice. KO mice displayed increased expression of thermogenic genes (Ucp1, P<0.05; Glut4, P<0.05; Cox4, P<0.01) in BAT and a decreased expression of adipogenic genes (Pparγ, P<0.05; Fabp4, P<0.05; Glut4, P<0.05) in VAT compared with WT mice, indicative of augmented energy expenditure.Conclusions:Genetic eviction of macroH2A1 confers protection against diet-induced obesity and metabolic derangements in mice. Inhibition of macroH2A1 might be a helpful strategy for epigenetic therapy of obesity.

AB - AbstractBackground/objectives:In the context of obesity, epigenetic mechanisms regulate cell-specific chromatin plasticity, perpetuating gene expression responses to nutrient excess. MacroH2A1, a variant of histone H2A, emerged as a key chromatin regulator sensing small nutrients during cell proliferation and differentiation. Mice genetically ablated for macroH2A1 (knockout (KO)) do not show overt phenotypes under a standard diet. Our objective was to analyse the in vivo role of macroH2A1 in response to nutritional excess.Methods:Twelve-week-old whole-body macroH2A1 KO male mice were given a high-fat diet (60% energy from lard) for 12 weeks until being killed, and examined for glucose and insulin tolerance, and for body fat composition. Energy expenditure was assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in the brown adipose tissue (BAT) or in adipogenesis in the visceral adipose tissue (VAT).Results:Under a chow diet, macroH2A1 KO mice did not differ from their wild-type (WT) littermates for body weight, and for sensitivity to glucose or insulin. However, KO mice displayed decreased heat production (P<0.05), and enhanced total activity during the night (P<0.01). These activities related to protection against diet-induced obesity in KO mice, which displayed decreased body weight owing to a specific decrease in fat mass (P<0.05), increased tolerance to glucose (P<0.05), and enhanced total activity during the day (P<0.05), compared with WT mice. KO mice displayed increased expression of thermogenic genes (Ucp1, P<0.05; Glut4, P<0.05; Cox4, P<0.01) in BAT and a decreased expression of adipogenic genes (Pparγ, P<0.05; Fabp4, P<0.05; Glut4, P<0.05) in VAT compared with WT mice, indicative of augmented energy expenditure.Conclusions:Genetic eviction of macroH2A1 confers protection against diet-induced obesity and metabolic derangements in mice. Inhibition of macroH2A1 might be a helpful strategy for epigenetic therapy of obesity.

UR - http://hdl.handle.net/10447/96619

M3 - Article

VL - 39

SP - 331

EP - 338

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

ER -