*2.3.3. 24-Hydroxylation*

Vitamin D 24-hydroxylase (CYP24A1) is responsible for the inactivation of 1,25(OH)2D. This inactivation is self-regulated, from 1,25(OH)2D induces the expression of CYP24A1 which converts 25(OH)D in 1,25(OH)2D within the less active metabolites (24,25(OH)2D and 1,24,25(OH)3D), which are later catabolized into inactive calcitroic acid [53]. In AT, the expression of CYP24A1 has been detected in murine and human adipocytes. Additionally, levels of CYP24A1 mRNA are strongly induced by incubation of 1,25(OH)2D.

The expression of 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) genes and 24-hydroxylase enzyme has been shown in human adipocytes [17]. The CYP24 gene, which encodes the enzyme catalyzing 1,25(OH)2D, was also found to be expressed by human adipocytes and preadipocytes [31, 54]. Recently, a low expression of CYP27B1 gene in SAT of obese individuals has been shown [52]; this finding corroborates the ability of AT to metabolize VD locally. One of the main mechanisms by which this vitamin may act in human AT is via the expression of VD-metabolizing enzymes such as 25-hydroxylase CYP2J2, CYP27B1, and CYP24 [55]. This capacity to metabolize VD locally was demonstrated when, after weight loss in obese subjects, plasma 25(OH)D increased and expression levels of 25-hydroxylase CYP2J2 and 1α-hydroxylase CYP27B1 declined in the SAT of these subjects. So, a dynamic alteration may occur in AT during weight loss and obesity.

In the SAT of the obese individuals have a lower expression of one of the enzymes responsible for 25-hydroxylation of VD (CYP2J2), as well as a tendency toward a decreased expression of the 1α-hydroxylase, 25-hydroxylation and the 1α-hydroxylation in SAT are impaired in obesity AT expresses the enzymes for both the formation of 25(OH)D and of 1,25(OH)2D, and for degradation of VD. To explain an altered VD metabolism in obesity, major differences between SAT and VAT in the expression of VD-metabolizing enzymes occur with difference in spreading between lean and obese subjects [52]. The expression of CYP27A1 is more pronounced in VAT than in SAT, without differences between lean and obese women, while the expression of CYP2J2 is more prominent in SAT than in VAT in lean women. So, these findings lead to a compromised of 25-hydroxylation in SAT in obese, taken by a lower expression of the CYP2J2.
