Xenobiotic-Metabolizing Cytochromes P450 in Human White Adipose Tissue: Expression and Induction

Ellero, Sandrine L.; Chakhtoura, Ghassan; Barreau, Corinne; Langouët, Sophie; Benelli, C; Pénicaud, Luc; Beaune, Philippe; Waziers, Isabelle de

doi:10.1124/dmd.109.029249

Cited by 51 publications

(37 citation statements)

References 39 publications

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“…CYP3A4 25-hydroxylates vitamin D 2 , but not vitamin D 3 . 30 CYP3A4 was expressed in small amounts in SAT and VAT in the study by Ellero et al, 38 but was not detectable in our samples. As a control we tested the expression in liver cells and found a high level of expression, and therefore, we are confident that no CYP3A4 is expressed in our AT samples.…”

Section: Discussionmentioning

confidence: 66%

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

et al. 2012

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OBJECTIVE: Low vitamin D (VD) levels are common in obesity. We hypothesized that this may be due to metabolism of VD in adipose tissue (AT). Thus, we studied (1) whether the VD-metabolizing enzymes were expressed differently in AT of lean and obese individuals and in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and (2) whether their expression was influenced by weight loss. METHODS: Samples of SAT and VAT were analyzed for expression of the vitamin-D-25-hydroxylases CYP2R1, CYP2J2, CYP27A1 and CYP3A4, the 25-vitamin-D-1a-hydroxylase CYP27B1, the catabolic vitamin-D-24-hydroxylase CYP24A1, and the vitamin D receptor, using reverse transcriptase-PCR. Moreover, plasma 25-hydroxy-vitamin D (25OHD) level was measured and related to the expression of these enzymes. Samples of SAT and VAT from 20 lean women and 20 obese women, and samples of SAT from 17 obese subjects before and after a 10% weight loss were analyzed. RESULTS: A plasma 25OHD level o50 nmol l À 1 was highly prevalent in both lean (45%) and obese (90%) women (Po0.01). Plasma 25OHD increased by 27% after weight loss in the obese individuals (Po0.05). Expression levels of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 were decreased by 71% (Po0.0001) and 49% (Po0.05), respectively, in SAT of the obese. CYP24A1 did not differ between lean and obese women, but the expression was increased by 79% (Po0.05) after weight loss. CONCLUSION: Obesity is characterized by a decreased expression of the 25-hydroxylase CYP2J2 and the 1a-hydroxylase CYP27B1 in SAT, whereas the catabolic CYP24A1 does not differ between lean and obese women. However, the expression of CYP24A1 is increased after weight loss. Accordingly, AT has the capacity to metabolize VD locally, and this can be dynamically altered during obesity and weight loss. INTRODUCTIONLow levels of circulating 25-hydroxy-vitamin D (25OHD) are associated with increased fat mass and body mass index, 1-5 but the underlying mechanism for this association is not fully elucidated. 6 Vitamin D (VD) is stored in adipose tissue (AT), and release of VD from AT is proposed to serve as an endogenous source of VD during the winter, when cutaneous production is low or absent in several parts of the world. 7 As low circulating levels of 25OHD are common in association with the obese state, 8 several studies have examined the effect of weight loss on circulating levels of 25OHD. However, results are inconsistent. After diet-and exercise-induced weight loss, both increased 9-11 and unaltered 12,13 circulating levels of 25OHD have been reported. Likewise, after major weight loss by bariatric surgery, both temporary 14-16 and long-term increases [16][17][18] in circulating levels of 25OHD have been reported, along with reports of no changes one year after surgery. 13,19 Taken together, these findings indicate that body weight is an important factor for circulating 25OHD levels. Several other explanations for the low levels of 25OHD in obesity have been proposed: a decreased exposure to sun light, 20 ...

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Section: Discussionmentioning

confidence: 66%

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

et al. 2012

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“…Among them, CYP1B1 and CYP2U1 were the most highly expressed xenobiotic-metabolizing CYPs in both adipose depots of all individuals (100). Surprisingly, the mRNA level of CYP1B1 and CYP2U1 in adipose tissue was even higher than that in the liver (100).…”

Section: Xenobiotic-metabolizing Enzymes In Adipose Tissuementioning

confidence: 79%

“…Surprisingly, the mRNA level of CYP1B1 and CYP2U1 in adipose tissue was even higher than that in the liver (100). The expression of these CYPs is inducible by xenobiotics in the liver (226), a common cellular mechanism leading to detoxification of many endogenous and exogenous compounds (227).…”

Section: Xenobiotic-metabolizing Enzymes In Adipose Tissuementioning

confidence: 98%

Steroid biosynthesis in adipose tissue

2015

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“…2009; Thelen and Dressman 2009; Ellero et al. 2010; Knights et al. 2013; Ravindranath and Strobel 2013).…”

Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

188

161

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Drug‐induced toxicity is a key issue for public health because some side effects can be severe and life‐threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug‐induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug‐induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug‐induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.

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Xenobiotic-Metabolizing Cytochromes P450 in Human White Adipose Tissue: Expression and Induction

Cited by 51 publications

References 39 publications

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss

Steroid biosynthesis in adipose tissue

Role of endoplasmic reticulum stress in drug‐induced toxicity

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