De Novo Synthesis of Steroids and Oxysterols in Adipocytes

Abstract

Background: Adipocytes are known to metabolize but not synthesize de novo steroids or oxysterols. Results: CYP11A1 in adipocytes is able to synthesize pregnenolone; 27-hydroxycholesterol (27HC) is a major cholesterol metabolite in adipocytes exhibiting anti-adipogenic activity. Conclusion: Adipocytes have the ability to synthesize steroids and oxysterols de novo. Significance: Formation of 27HC in adipocytes may prevent the enlargement of adipose tissue compartment.

Redox modulation of adipocyte differentiation: hypothesis of “Redox Chain” and novel insights into intervention of adipogenesis and obesity

“…In addition, CYP2E1 expression and activity are increased in female ob/ob mice, while that of CYP1A2 are decreased in male ob/ob mice regardless of gender [226]. Inhibition of CYP27A1 activity, or KD and/or deletion of the Cyp27a1 gene induce adipocyte differentiation through regulating oxysterol 27-hydroxycholesterol [227]. During the differentiation of MSCs to adipocytes, CYP4A11 and CYP4F2 expression are decreased to nearly undetectable level [210].…”

2β- and 16β-hydroxylase activity of CYP11A1 and direct stimulatory effect of estrogens on pregnenolone formation

“…8 They are synthesized in steroidogenic tissues or organs, such as the 9 adrenal glands or the gonads, in a series of reactions involving six 10 different cytochromes P450 (CYPs) [1][2][3]. Steroid hormones are 11 categorized into three main classes: the mineralocorticoids and 12 glucocorticoids, regulating the salt and sugar homeostasis, 13 respectively, as well as the sex hormones, which are necessary 14 for the development of the secondary sexual characteristics and for 15 reproduction [2,4]. Their availability is regulated by complicated 16 mechanisms at different levels.…”

“…Q2 29 The biosynthesis of steroid hormones starts with the side-chain 30 cleavage of cholesterol producing pregnenolone. This is the first 31 enzymatic and rate-limiting step and is catalyzed by the side-chain 32 cleaving cytochrome P450CYP11A1 [10,11], a mitochondrial cyto- 33 chrome P450 found primarily in the steroidogenic cells of the 34 adrenal cortex and the gonads as well as in the skin and brain [12]. 35 The side chain cleavage of cholesterol by CYP11A1 is performed 36 through three consecutive steps: two hydroxylations at C22 and 37 C20, respectively, followed by the cleavage of the C20-C22 bond 38 [2,10,13].…”

Fucoxanthin and lipid metabolism: A minireview

“…Adipose tissue is currently recognized as a major endocrine organ in the production and secretion of leptin, adiponectin, resistin, estrogen, secretin, steroids, cytokine TNFα, and other bioactive compounds [6,7]. Furthermore, specific adipocytes in adipose tissue play an important role in the determination of metabolic rate.…”