Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes

Veilleux, Alain; Côté, Julie-Anne; Blouin, Karine; Nadeau, Mélanie; Pelletier, Mélissa; Marceau, Picard; Laberge, Philippe Y.; Luu‐The, Van; Tchernof, André

doi:10.1152/ajpendo.00069.2011

Cited by 33 publications

(25 citation statements)

References 30 publications

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“…The androgen dihydrotestosterone (DHT) inhibits adipocyte differentiation in humans (Blouin et al 2009b). Studies show that an increased expression or activation of AKR1C2 induces adipocyte differentiation by inactivating DHT (Blouin et al 2009a;Veilleux et al 2012). Previously, we found that AKR1C2 protein expression after weight loss/maintenance was increased and that the increase correlated with changes in parameters of adiposity including weight, BMI, waist and plasma LDL ).…”

Section: Discussionmentioning

confidence: 99%

“…However, as we matched for age, the proportion was the same for the weight stable (39/127) and the weight gainers group (40/117) suggesting a minimal effect on our results. AKR1C2 plays a role in the crosstalk between glucocorticoids and androgens as part of the regulation of adipogenesis and lipid accumulation (Veilleux et al 2012). The androgen dihydrotestosterone (DHT) inhibits adipocyte differentiation in humans (Blouin et al 2009b).…”

Section: Discussionmentioning

confidence: 99%

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Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period

et al. 2014

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Weight gain, when it leads to overweight or obesity, is nowadays one of the major health problems. ACE, FTO, AKR1C2, TIMP4 and MMP2 genes have been implicated in previous studies on weight regulation. This study investigated the contribution of polymorphisms in these five candidate genes to the risk of weight gain over a 10-year time period. Two groups were selected from participants of the Doetinchem cohort study who were followed over a 10-year period: A stable weight group (±2 kg/10 year; n = 259) and a weight gainers group who increased their body weight by roughly 10 % ([8 kg/ 10 year; n = 237). Starting BMI was between 20 and 35 kg/m 2 and baseline age between 20 and 45 years. Selected SNPs and insert/deletion in candidate genes were measured in each group. In men, the allelic distribution of FTO rs9939609 (v 2 p = 0.005), ACE rs4340 (v 2 p = 0.006) and AKR1C2 rs12249281 (v 2 p = 0.019) differed between the weight stable and weight gainers group. Interaction between FTO rs9939609 and ACE rs4340 was observed. In women, the allelic distribution of MMP2 rs1132896 differed between the weight stable and weight gainers group (v 2 p = 0.00001). The A-allele of FTO was associated with a 1.999 higher risk of gaining weight in men (OR 1.99, p = 0.020), while in women, the C-allele of MMP2 was associated with a 2.509 higher risk of weight gain (OR 2.50, p = 0.001) over the 10-year period. We found that FTO in men and MMP2 in women are associated with weight gain over a 10-year follow-up period.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period

et al. 2014

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“…Glucocorticoids, in addition to reducing blood testosterone levels [10] , reduce DHT levels by decreasing 5α-reductase 1 in hepatocytes [55] and inactivate DHT by inducing aldo-keto reductase 1C2 in adipocytes [54] . In muscular cells in vivo, administration of glucocorticoids reduces AR expression and administration of androgens reduces GR expression [10,36] .…”

Section: Discussionmentioning

confidence: 99%

“…However, it is difficult to conclude that this reduction is due to the suppression of glucocorticoid signaling because differentiation of 3T3-L1 is needed for the activations of other types of signaling (e.g., insulin signaling and PKA signaling by isobutylmethylxanthine). Glucocorticoids inactivate DHT by inducing the expression of aldo-keto reductase 1C2, which metabolizes DHT to 5α-androstane-3α, 17β-diol [54] , reducing the overall function of DHT in adipocytes. Although androgens and glucocorticoids have at least partially opposing effects on lipolysis in adipocytes and the differentiation of preadipocytes, the mechanism underlying the competition remains largely unknown.…”

Section: Lipid Metabolism In and Adipose Tissue And Livermentioning

confidence: 99%

Competitive and compensatory effects of androgen signaling and glucocorticoid signaling

Harada

Inui

Yamaji

2015

Receptor Clin Invest

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Androgens and glucocorticoids have competitive and compensatory effects in several physiological and pathophysiological processes. Although blood androgen levels affect blood glucocorticoid levels and vice versa, it does not fully explain the relationship between the effects of androgens and glucocorticoids. Androgens and glucocorticoids exert their functions through binding to androgen receptor (AR) and glucocorticoid receptor (GR), respectively. AR homodimer and GR homodimer bind to the androgen response element (ARE) and glucocorticoid response element (GRE), respectively, where they positively or negatively regulate transcription. AR/GR heterodimer can also form but whether it has a physiological role is unclear. Notably, some ARE/GRE sites are recognized by both AR and GR. This review focuses on the functional interventions between androgen signaling and glucocorticoid signaling in target cells that are involved in muscle atrophy, lipid metabolism in adipocytes and hepatocytes, and pancreatic β-cell death. Androgens and glucocorticoids exert opposite effects by differentially regulating key genes (e.g., insulin-like growth factor-1, atrogin-1, and thioredoxin-interacting protein) involved in these physiological processes. We also review functional compensation between these steroids in the development of castration-resistant prostate cancer in which glucocorticoids compensate for the castration-induced loss of AR function by activating key genes (e.g., serum/glucocorticoid-regulated kinase 1). The gene expressions regulated by androgens and glucocorticoids are regulated through at least three different mechanisms in target cells: (i) regulation of applicable ligand levels by modulation of steroid metabolite enzyme levels, (ii) regulation of each other's receptor levels, and (iii) competitive binding between AR and GR on ARE/GRE sites. Recent findings shed light on the complicated relationship between androgen signaling and glucocorticoid signaling in various cellular processes.

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“…Накопление жира в ор-ганизме происходит в результате его отложения в подкожных и висцеральных депо. При ожирении вначале преимущественно увеличивается подкож-ное депо [29], но затем жир преимущественно нака-пливается в висцеральных депо. Предполагается, что избыток висцерального жира может быть связан с расторможенностью гипоталамо-гипофизарно-надпочечниковой оси, приводящей к гиперпродук-ции глюкокортикоидных гормонов [30].…”

Section: существуетunclassified

Is visceral obesity the cause of obesity paradox?

Бородкина¹,

Груздева²,

Квиткова³

et al. 2017

Probl Endokrinol (Mosk)

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Ожирение является одной из важнейших про-блем здравоохранения, а масштабность его распро-странения носит характер эпидемии. Так, в России более 60% населения имеют избыточную массу тела, а около 26% страдают ожирением [1]. Ожирение встречается у каждого третьего жителя США [2], почти половина европейцев имеют избыточную массу тела (54,5% мужчин и 40,8% женщин), а у каждого десятого диагностируют ожирение (14,0% мужчин и 11,5% женщин) [3]. Несмотря на то что темп роста распространенности ожирения замед-лился в последнее время, общее число лиц, страда-ющих ожирением, вызывает тревогу, учитывая фи-нансовые и медицинские последствия [4].Ожирение относится к числу 10 основных факто-ров риска смерти [5]. Многие эпидемиологические исследования продемонстрировали ассоциацию между тяжелыми формами ожирения и распростра-ненностью сердечно-сосудистых заболеваний, а так-же смертностью от них [6][7][8]. По данным ВОЗ [9], избыточная масса тела и ожирение предопределяют развитие до 44% всех случаев сахарного диабета 2-типа (СД2) и до 23% случаев ишемической болезни сердца (ИБС). Согласно отчетам фремингемского исследования сердца [10], у пациентов с ожирением риск сердечной недостаточности в 2 раза выше, чем у лиц с нормальной массой тела. При этом повышение индекса массы тела (ИМТ) на каждую единицу уве-личивает риск на 5% для мужчин и на 7% для жен-щин. По данным «Nurses Health Study», при ИМТ более 32 кг/м 2 относительный риск кардиоваскуляр-ных заболеваний в 4,1 раза превышает таковой при ИМТ 19 кг/м 2 [11]. Кроме того, избыточная масса тела и ожирение у больных ИБС способствует ее про-грессированию и повышению смертности. При этом средний возраст, в котором развивается первый ин-фаркт миокарда (ИМ), снижается на 4-8 лет [12]. Ожирение относится к числу 10 основных факторов риска смерти. Согласно эпидемиологическим исследованиям, избы-точная масса тела и ожирение предопределяют развитие почти 44% случаев сахарного диабета 2-го типа (СД2) и до 23% случаев ишемической болезни сердца (ИБС). Ожирение и избыточный вес традиционно оцениваются по индексу массы тела (ИМТ). Однако в последние годы появляется все больше работ о «парадоксе» ожирения. Так, у лиц с ожирением отдаленный прогноз инфаркта миокарда (ИМ), острого нарушения мозгового кровообращения (ОНМК) и хронической сердечной недостаточности (ХСН) более благоприятен, чем у лиц без избытка массы тела. Наибольший риск сердеч-но-сосудистых заболеваний связан с висцеральным ожирением и характерными для него метаболическими сдвигами (инсулинорезистентностью, гипергликемией, дислипидемией, дисбалансом адипокинов и маркеров воспаления). Эти из-менения при висцеральном ожирении могут наблюдаться независимо от величины ИМТ. Obesity is one of the 10 risk factors of death. Many epidemiological studies have shown that overweight and obesity are associated with 44% cases of diabetes type 2, and 23% of cases of coronary heart disease. The body mass index (BMI) is traditionally a diagnostic marker of obesity and overweight are considered. However, in the last 15 years, there has been w...

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Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes

Cited by 33 publications

References 30 publications

Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period

Gender-specific genetic associations of polymorphisms in ACE, AKR1C2, FTO and MMP2 with weight gain over a 10-year period

Competitive and compensatory effects of androgen signaling and glucocorticoid signaling

Is visceral obesity the cause of obesity paradox?

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