Increased estrogen receptor β in adipose tissue is associated with increased intracellular and reduced circulating adiponectin protein levels in aged female rats

Nanette J. Tomicek, Timothy S. Lancaster, Donna H. Korzick

Research output: Contribution to journalArticle

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Abstract

Background: Obesity and associated metabolic and cardiovascular disease risk are correlated with reduced circulating adiponectin (APN) levels. Metabolic and cardiovascular disease risk is also increased after menopause and may be linked to disturbances in estrogen receptor (ER) signaling in adipose. Objective: We hypothesized thatage-associated estrogen (E 2)- deficiency alters the ERα/β ratio in adipose tissue and increases risk for metabolic disease via APN-ac activated mechanisms. Methods: Visceral adipose was isolated from adult (6 months)and aged (24 months) female Fisher 344 rats (n = 56/group) with ovaries intact or removed by surgical ovariectomy (OVX) and subjected to western blotting. Results: Notably, weight was greatest in aged OVX rats (P < 0.01) and associated with a 2-fold increase in ERβ protein versus adult intact rats (P < 0.001). ER levels were increased in aged OVX versus adult OVX rats. Intra-adipocyte APN was also increased in aged OVX rats versus all groups (P < 0.01), whereas circulating APN levels decreased in aged OVX versus adult OVX rats (P < 0.05). Endoplasmic reticulum protein of 44 kDa (Erp44) levels remained the same (P = 0.09). Adiponectin receptor-1 (AdipoR1) and peroxisome proliferator-activated receptor-α (PPAR-α) were also unchanged. AdipoR2, PPAR-γ, and phosphorylated adenosine monophosphate-dependant kinase (pAMPK) to total AMPK ratio all decreased with age (P < 0.05). Conclusions: Collectively, these data suggested that age-associated increases in ERβ paired with decreased PPAR-γ levels might predispose E 2-deficient postmenopausal women for increased adiposity and associated metabolic and cardiovascular disease risk. Reduced circulating APN and AdipoR2 levels might contribute to age and E 2-deficiency linked disease progression.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalGender Medicine
Volume8
Issue number5
DOIs
StatePublished - Oct 1 2011

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Adiponectin
Estrogen Receptors
Adipose Tissue
Metabolic Diseases
Disease
Peroxisome Proliferator-Activated Receptors
Proteins
Cardiovascular Diseases
Adiponectin Receptors
menopause
Deficiency Diseases
AMP-Activated Protein Kinases
Adiposity
Ovariectomy
Adenosine Monophosphate
Menopause
Adipocytes
Endoplasmic Reticulum
Group
Disease Progression

All Science Journal Classification (ASJC) codes

  • Gender Studies

Cite this

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title = "Increased estrogen receptor β in adipose tissue is associated with increased intracellular and reduced circulating adiponectin protein levels in aged female rats",
abstract = "Background: Obesity and associated metabolic and cardiovascular disease risk are correlated with reduced circulating adiponectin (APN) levels. Metabolic and cardiovascular disease risk is also increased after menopause and may be linked to disturbances in estrogen receptor (ER) signaling in adipose. Objective: We hypothesized thatage-associated estrogen (E 2)- deficiency alters the ERα/β ratio in adipose tissue and increases risk for metabolic disease via APN-ac activated mechanisms. Methods: Visceral adipose was isolated from adult (6 months)and aged (24 months) female Fisher 344 rats (n = 56/group) with ovaries intact or removed by surgical ovariectomy (OVX) and subjected to western blotting. Results: Notably, weight was greatest in aged OVX rats (P < 0.01) and associated with a 2-fold increase in ERβ protein versus adult intact rats (P < 0.001). ER levels were increased in aged OVX versus adult OVX rats. Intra-adipocyte APN was also increased in aged OVX rats versus all groups (P < 0.01), whereas circulating APN levels decreased in aged OVX versus adult OVX rats (P < 0.05). Endoplasmic reticulum protein of 44 kDa (Erp44) levels remained the same (P = 0.09). Adiponectin receptor-1 (AdipoR1) and peroxisome proliferator-activated receptor-α (PPAR-α) were also unchanged. AdipoR2, PPAR-γ, and phosphorylated adenosine monophosphate-dependant kinase (pAMPK) to total AMPK ratio all decreased with age (P < 0.05). Conclusions: Collectively, these data suggested that age-associated increases in ERβ paired with decreased PPAR-γ levels might predispose E 2-deficient postmenopausal women for increased adiposity and associated metabolic and cardiovascular disease risk. Reduced circulating APN and AdipoR2 levels might contribute to age and E 2-deficiency linked disease progression.",
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Increased estrogen receptor β in adipose tissue is associated with increased intracellular and reduced circulating adiponectin protein levels in aged female rats. / Tomicek, Nanette J.; Lancaster, Timothy S.; Korzick, Donna H.

In: Gender Medicine, Vol. 8, No. 5, 01.10.2011, p. 325-333.

Research output: Contribution to journalArticle

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T1 - Increased estrogen receptor β in adipose tissue is associated with increased intracellular and reduced circulating adiponectin protein levels in aged female rats

AU - Tomicek, Nanette J.

AU - Lancaster, Timothy S.

AU - Korzick, Donna H.

PY - 2011/10/1

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N2 - Background: Obesity and associated metabolic and cardiovascular disease risk are correlated with reduced circulating adiponectin (APN) levels. Metabolic and cardiovascular disease risk is also increased after menopause and may be linked to disturbances in estrogen receptor (ER) signaling in adipose. Objective: We hypothesized thatage-associated estrogen (E 2)- deficiency alters the ERα/β ratio in adipose tissue and increases risk for metabolic disease via APN-ac activated mechanisms. Methods: Visceral adipose was isolated from adult (6 months)and aged (24 months) female Fisher 344 rats (n = 56/group) with ovaries intact or removed by surgical ovariectomy (OVX) and subjected to western blotting. Results: Notably, weight was greatest in aged OVX rats (P < 0.01) and associated with a 2-fold increase in ERβ protein versus adult intact rats (P < 0.001). ER levels were increased in aged OVX versus adult OVX rats. Intra-adipocyte APN was also increased in aged OVX rats versus all groups (P < 0.01), whereas circulating APN levels decreased in aged OVX versus adult OVX rats (P < 0.05). Endoplasmic reticulum protein of 44 kDa (Erp44) levels remained the same (P = 0.09). Adiponectin receptor-1 (AdipoR1) and peroxisome proliferator-activated receptor-α (PPAR-α) were also unchanged. AdipoR2, PPAR-γ, and phosphorylated adenosine monophosphate-dependant kinase (pAMPK) to total AMPK ratio all decreased with age (P < 0.05). Conclusions: Collectively, these data suggested that age-associated increases in ERβ paired with decreased PPAR-γ levels might predispose E 2-deficient postmenopausal women for increased adiposity and associated metabolic and cardiovascular disease risk. Reduced circulating APN and AdipoR2 levels might contribute to age and E 2-deficiency linked disease progression.

AB - Background: Obesity and associated metabolic and cardiovascular disease risk are correlated with reduced circulating adiponectin (APN) levels. Metabolic and cardiovascular disease risk is also increased after menopause and may be linked to disturbances in estrogen receptor (ER) signaling in adipose. Objective: We hypothesized thatage-associated estrogen (E 2)- deficiency alters the ERα/β ratio in adipose tissue and increases risk for metabolic disease via APN-ac activated mechanisms. Methods: Visceral adipose was isolated from adult (6 months)and aged (24 months) female Fisher 344 rats (n = 56/group) with ovaries intact or removed by surgical ovariectomy (OVX) and subjected to western blotting. Results: Notably, weight was greatest in aged OVX rats (P < 0.01) and associated with a 2-fold increase in ERβ protein versus adult intact rats (P < 0.001). ER levels were increased in aged OVX versus adult OVX rats. Intra-adipocyte APN was also increased in aged OVX rats versus all groups (P < 0.01), whereas circulating APN levels decreased in aged OVX versus adult OVX rats (P < 0.05). Endoplasmic reticulum protein of 44 kDa (Erp44) levels remained the same (P = 0.09). Adiponectin receptor-1 (AdipoR1) and peroxisome proliferator-activated receptor-α (PPAR-α) were also unchanged. AdipoR2, PPAR-γ, and phosphorylated adenosine monophosphate-dependant kinase (pAMPK) to total AMPK ratio all decreased with age (P < 0.05). Conclusions: Collectively, these data suggested that age-associated increases in ERβ paired with decreased PPAR-γ levels might predispose E 2-deficient postmenopausal women for increased adiposity and associated metabolic and cardiovascular disease risk. Reduced circulating APN and AdipoR2 levels might contribute to age and E 2-deficiency linked disease progression.

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