Essential roles of 11β-HSD1 in regulating brown adipocyte function

Liu, Juan; Kong, Xu; Wang, Long; Qi, Hanmei; Di, Wenjuan; Zhang, Xiao; Wu, Lin; Chen, Xia; Yu, Jing; Zha, Juanmin; Lv, Shan; Zhang, Aisen; Peng, Cheng; Hu, Miao; Li, Yujie; Bi, Jianhua; Li, Yan; Hu, Fang; Zhong, Yi; Xu, Yong

doi:10.1530/jme-12-0099

Cited by 38 publications

(30 citation statements)

References 34 publications

(35 reference statements)

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“…Consistent with these findings, gene expression of MR was upregulated in WAT of obese mice (56). It has been reported that 11␤-HSD1 inhibition decreased WAT mass, adipocyte hypertrophy, and adipose tissue fibrosis (113), whereas it increased the expression of BAT-specific genes (including UCP1) in obese rats (73).…”

Section: Adipose Tissue Local Factors: Potential Implications Of the supporting

confidence: 79%

Nutritional manipulations in the perinatal period program adipose tissue in offspring

Lukaszewski

Eberlé

Vieau

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Epidemiological studies demonstrated initially that maternal undernutrition results in low birth weight with increased risk for long-lasting energy balance disorders. Maternal obesity and diabetes associated with high birth weight, excessive nutrition in neonates, and rapid catchup growth also increase the risk of adult-onset obesity. As stated by the Developmental Origin of Health and Disease concept, nutrient supply perturbations in the fetus or neonate result in long-term programming of individual body weight set point. Adipose tissue is a key fuel storage unit involved mainly in the maintenance of energy homeostasis. Studies in numerous animal models have demonstrated that the adipose tissue is the focus of developmental programming events in a sex- and depot-specific manner. In rodents, adipose tissue development is particularly active during the perinatal period, especially during the last week of gestation and during early postnatal life. In contrast to rodents, this process essentially takes place before birth in bigger mammals. Despite these different developmental time windows, altricial and precocial species share several mechanisms of adipose tissue programming. Offspring from malnourished dams present adipose tissue with a series of alterations: impaired glucose uptake, insulin and leptin resistance, low-grade inflammation, modified sympathetic activity with reduced noradrenergic innervations, and thermogenesis. These modifications reprogram adipose tissue metabolism by changing fat distribution and composition and by enhancing adipogenesis, predisposing the offspring to fat accumulation. Subtle adipose tissue circadian rhythm changes are also observed. Inappropriate hormone levels, modified tissue sensitivity (especially glucocorticoid system), and epigenetic mechanisms are key factors for adipose tissue programming during the perinatal period.

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Section: Adipose Tissue Local Factors: Potential Implications Of the supporting

confidence: 79%

Nutritional manipulations in the perinatal period program adipose tissue in offspring

Lukaszewski

Eberlé

Vieau

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…Dexamethasone significantly reduced the isoprenaline-induced OCR of brown adipocytes, the major component of which was uncoupled oxidation. These observations on human brown adipocytes are supported by results from studies on rodents (Soumano et al 2000, Rodríguez & Palou 2004, Liu et al 2013. The stimulation, by exposure to cold or isoprenaline, of expression of UCP1 of BAT from the intrascapular region is inhibited by GCs (Soumano et al 2000).…”

Section: Figuresupporting

confidence: 53%

Effects of glucocorticoids on human brown adipocytes

Barclay¹,

Agada²,

Jang³

et al. 2014

Journal of Endocrinology

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Clinical cases of glucocorticoid (GC) excess are characterized by increased fat mass and obesity through the accumulation of white adipocytes. The effects of GCs on growth and function of brown adipose tissue are unknown and may contribute to the negative energy balance observed clinically. This study aims to evaluate the effect of GCs on proliferation, differentiation, and metabolic function of brown adipocytes. Human brown adipocytes sourced from supraclavicular fat biopsies were grown in culture and differentiated to mature adipocytes. Human white adipocytes sourced from subcutaneous abdominal fat biopsies were cultured as controls. Effects of dexamethasone on growth, differentiation (UCP1, CIDEA, and PPARGC1A expression), and function (oxygen consumption rate (OCR)) of brown adipocytes were quantified. Dexamethasone (1 mM) significantly stimulated the proliferation of brown preadipocytes and reduced that of white preadipocytes. During differentiation, dexamethasone (at 0.1, 1, and 10 mM) stimulated the expression of UCP1, CIDEA, and PPARGC1A in a concentration-dependent manner and enhanced by fourfold to sixfold the OCR of brown adipocytes. Isoprenaline (100 nM) significantly increased (P!0.05) expression of UCP1 and OCR of brown adipocytes. These effects were significantly reduced (P!0.05) by dexamethasone. Thus, we show that dexamethasone stimulates the proliferation, differentiation, and function of human brown adipocytes but inhibits adrenergic stimulation of the functioning of brown adipocytes. We conclude that GCs exert complex effects on development and function of brown adipocytes. These findings provide strong evidence for an effect of GCs on the biology of human brown adipose tissue (BAT) and for the involvement of the BAT system in the metabolic manifestation of Cushing's syndrome.

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“…Consistent with these findings, the MR mRNA expression levels were significantly upregulated in the WAT of the obese mice [102]. Third, the 11β-HSD1 inhibition decreased the WAT mass, adipocyte hypertrophy, and adipose tissue fibrosis [103,104], whereas it increased the expression of the BAT-specific genes (including UCP1) in the obese rats [105]. Four, we confirmed the presence of the MR mRNA in the WAT of the adult rats.…”

Section: Actions Of Glucocorticoids In Adipose Tissue Activitysupporting

confidence: 78%

Role of maternal nutrition in programming adiposity in the offspring: potential implications of glucocorticoids

Breton

2013

Hormone Molecular Biology and Clinical Investigation

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The epidemiological studies initially indicated that maternal undernutrition leading to a low birth weight may predispose to the long-lasting energy balance disorders. A high birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to an increased risk of obesity. As stated by the developmental origin of health and disease concept, the perinatal perturbation of the fetus/neonate nutrient supply might be a crucial determinant of the individual programming of the body weight set point. The adipose tissue is considered as the main fuel storage unit involved in the maintenance of the energy homeostasis. Several models have demonstrated that this tissue is a prime target of the developmental programming in a gender- and depot-specific manner. In the rodents, the perinatal period of life corresponds largely to the period of adipogenesis. In contrast, this phenomenon essentially takes place before birth in bigger mammals. Despite these different developmental time windows, the altricial and precocial species share several common offspring programming mechanisms. Thus, the adipose tissue of the offspring from malnourished dams exhibited impaired glucose uptake and leptin/insulin resistance with increased proinflammatory markers. It also displayed a modified sympathetic activity, circadian rhythm, fatty acid composition, and thermogenesis. This might lead to the reprogrammed metabolism and distribution of the adipose tissue with enhanced adipogenesis and fat accumulation predisposing to adiposity. The inappropriate glucocorticoid (GC) levels and modified tissue sensitivity might be key actors of perinatal programming and long-lasting altered adipose tissue activity in the offspring. Following maternal malnutrition, the epigenetic mechanisms might also be responsible for the adipose tissue programming.

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Essential roles of 11β-HSD1 in regulating brown adipocyte function

Cited by 38 publications

References 34 publications

Nutritional manipulations in the perinatal period program adipose tissue in offspring

Nutritional manipulations in the perinatal period program adipose tissue in offspring

Effects of glucocorticoids on human brown adipocytes

Role of maternal nutrition in programming adiposity in the offspring: potential implications of glucocorticoids

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