Obesity and Disturbed Lipoprotein Profile in Estrogen Receptor-α-Deficient Male Mice

Ohlsson, Claes; Hellberg, Nina; Parini, Paolo; Vidal, Olle; Bohlooly, Mohammed; Rudling, Mats; Lindberg, Mattias F.; Warner, Margaret; Angelin, Bo; Gustafsson, Jan‐Åke

doi:10.1006/bbrc.2000.3827

Cited by 300 publications

(244 citation statements)

References 51 publications

(40 reference statements)

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“…The effects of oestrogens are mediated by two receptors: ERα and ERβ. In ERKO, but not BERKO, body mass, fat deposition and cholesterol levels were increased [4]. Both male and female ERKO mice had IGT, supporting the hypothesis that the glucose-lowering effect of oestrogens is mediated by ERα [5].…”

Section: Introductionmentioning

confidence: 56%

“…In earlier studies, we have demonstrated that normalisation of blood glucose levels in diabetic GK rats restores insulin sensitivity, which we interpreted as indicating that glucotoxicity accounts for insulin resistance in the muscle [29]. Since ERKO mice show slightly increased NEFA levels [4], it is possible that lipotoxicity may also play a role in this context.…”

Section: Discussionmentioning

confidence: 73%

“…It is therefore possible that the reciprocal expression of Lepr and Scd1 may constitute an important mechanism underlying hepatic insulin resistance in ERKO mice. Ohlsson et al [4] demonstrated slightly increased plasma NEFA levels in ERKO mice. Therefore it is possible that the increased access of NEFA to the liver may also contribute to hepatic insulin resistance.…”

Section: Discussionmentioning

confidence: 95%

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Evidence that oestrogen receptor-α plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver

et al. 2006

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Aims/hypothesis: We used oestrogen receptor-α (ERα) knockout (ERKO) and receptor-β (ERβ) knockout (BERKO) mice to investigate the mechanism(s) behind the effects of oestrogens on glucose homeostasis. Methods: Endogenous glucose production (EGP) was measured in ERKO mice using a euglycaemic-hyperinsulinaemic clamp. Insulin secretion was determined from isolated islets. In isolated muscles, glucose uptake was assayed by using radiolabelled isotopes. Genome-wide expression profiles were analysed by high-density oligonucleotide microarray assay, and the expression of the genes encoding stearoyl-CoA desaturase 1 and the Leptin receptor (Scd1 and Lepr, respectively) was confirmed by RT-PCR. Results: ERKO mice had higher fasting blood glucose, plasma insulin levels and IGT. The plasma leptin level was increased, while the adiponectin concentration was decreased in ERKO mice. Levels of both glucose-and arginine-induced insulin secretion from isolated islets were similar in ERKO and wild-type mice. The euglycaemichyperinsulinaemic clamp revealed that suppression of EGP by increased insulin levels was blunted in ERKO mice, which suggests a pronounced hepatic insulin resistance. Microarray analysis revealed that in ERKO mice, the genes involved in hepatic lipid biosynthesis were upregulated, while genes involved in lipid transport were downregulated. Notably, hepatic Lepr expression was decreased in ERKO mice. In vitro studies showed a modest decrease in insulin-mediated glucose uptake in soleus and extensor digitorum longus (EDL) muscles of ERKO mice. BERKO mice demonstrated normal glucose tolerance and insulin release. Conclusions/interpretation: We conclude that oestrogens, acting via ERα, regulate glucose homeostasis mainly by modulating hepatic insulin sensitivity, which can be due to the upregulation of lipogenic genes via the suppression of Lepr expression.

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Section: Introductionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 95%

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Evidence that oestrogen receptor-α plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver

et al. 2006

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“…In studies of ERa, ERb (BERKO) and double (DERKO) KO models by Ohlsson et al, 20 fat mass was found to be decreased in BERKO compared with wild-type mice, which is in clear contrast with the effect of ERa invalidation. Furthermore, in studies of ovariectomized ERa KO, BERKO and DERKO mice, gonadal fat mass was found to be reduced by estrogen administration in wild-type and BERKO, but not in ERa KO and DERKO mice.…”

Section: Discussionmentioning

confidence: 97%

“…The increase in body weight was associated with an increased fat mass, in accordance with the ERa KO phenotype described in previous studies. 6,20 The mice used here were 5 months old at the beginning of the study and they did not gain much weight (1-2 g) during the 28-day study period. At the onset of the study, the ERa KO mice already weighed more than the wild-type animals and, in accordance with other studies, 6,7,20 were therefore well within the weight differentiation phase during which KO mice display higher body weight than the wild-type animals.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor α-mediated adiposity-lowering and hypocholesterolemic actions of the selective estrogen receptor modulator acolbifene

et al. 2005

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OBJECTIVE:The selective estrogen receptor (ER) modulator (SERM) acolbifene (ACOL), a potent and pure antiestrogen in the mammary gland and uterus, exerts beneficial pro-estrogenic actions on energy balance, insulin sensitivity and lipid metabolism. ACOL binds ERs a and b, both of which have been involved in the metabolic actions of estrogen. This study aimed at determining the identity of the ER involved in the beneficial metabolic actions of ACOL. DESIGN AND MEASUREMENTS: ACOL was administered for 4 weeks to male and female wild-type and ERa knockout (KO) mice, and indices of energy balance as well as plasma and liver lipid concentrations were determined. RESULTS: ERa KO mice were heavier, gained more fat mass and had larger adipose depots than their wild-type counterparts. In both genders, ACOL decreased fat gain (50%) and white adipose tissue mass in male and female wild-type, but not in ERa KO mice. ACOL reduced plasma cholesterol in female wild-type mice (À27%), whereas the compound remained ineffective in their ERa KO counterparts. Plasma triglycerides were unaffected by ACOL. Finally, ACOL decreased liver cholesterol and triglyceride concentrations only in wild-type female animals. CONCLUSION: The beneficial metabolic actions of the SERM ACOL on adiposity and on plasma and liver lipids are entirely due to its interaction with the ERa.

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Successful percutaneous closure of paraprosthetic aorto‐right ventricular leak using the Amplatzer duct occluder

Dussaillant

Romero

Ramírez

et al. 2006

Cathet Cardio Intervent

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A 55-year-old male with persisting aorto-right ventricular paraprosthetic leak after mitroaortic valve replacement was hospitalized for recurrent heart failure. Depressed left ventricular ejection fraction and severe pulmonary hypertension with increased right and left ventricular filling pressures were associated with significant left to right shunting through the leak. Elective closure of the leak was obtained with a 6-4 mm Amplatzer duct occluder. No complications were observed, and the patient experienced complete resolution of heart failure symptoms, with NYHA class I heart failure 12 months after discharge.

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Obesity and Disturbed Lipoprotein Profile in Estrogen Receptor-α-Deficient Male Mice

Cited by 300 publications

References 51 publications

Evidence that oestrogen receptor-α plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver

Evidence that oestrogen receptor-α plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver

Estrogen receptor α-mediated adiposity-lowering and hypocholesterolemic actions of the selective estrogen receptor modulator acolbifene

Successful percutaneous closure of paraprosthetic aorto‐right ventricular leak using the Amplatzer duct occluder

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