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

Adipogenesis and lipid storage in human adipose tissue are inhibited by androgens such as DHT. Inactivation of DHT to 3α-diol is stimulated by glucocorticoids in human preadipocytes. We sought to characterize glucocorticoid-induced androgen inactivation in human preadipocytes and to establish its role in the antiadipogenic action of DHT. Subcutaneous and omental primary preadipocyte cultures were established from fat samples obtained in subjects undergoing abdominal surgeries. Inactivation of DHT to 3α/β-diol for 24 h was measured in dexamethasone- or vehicle-treated cells. Specific downregulation of aldo-keto reductase 1C (AKR1C) enzymes in human preadipocytes was achieved using RNA interference. In whole adipose tissue sample, cortisol production was positively correlated with androgen inactivation in both subcutaneous and omental adipose tissue ( P < 0.05). Maximal dexamethasone (1 μM) stimulation of DHT inactivation was higher in omental compared with subcutaneous fat from men as well as subcutaneous and omental fat from women ( P < 0.05). A significant positive correlation was observed between BMI and maximal dexamethasone-induced DHT inactivation rates in subcutaneous and omental adipose tissue of men and women ( r = 0.24, n = 26, P < 0.01). siRNA-induced downregulation of AKR1C2, but not AKR1C1 or AKR1C3, significantly reduced basal and glucocorticoid-induced androgen inactivation rates ( P < 0.05). The inhibitory action of DHT on preadipocyte differentiation was potentiated following AKR1C2 but not AKR1C1 or AKR1C3 downregulation. Specifically, lipid accumulation, G3PDH activity, and FABP4 mRNA expression in differentiated preadipocytes exposed to DHT were reduced further upon AKR1C2 siRNA transfection. We conclude that glucocorticoid-induced androgen inactivation is mediated by AKR1C2 and is particularly effective in omental preadipocytes of obese men. The interplay between glucocorticoids and AKR1C2-dependent androgen inactivation may locally modulate adipogenesis and lipid accumulation in a depot-specific manner.

Changes in adipose tissue accumulation in Rasa Aragonesa breed lambs during growth and fattening

Changes during growth and fattening in the number and size of adipocytes and in the activity of the lipogenic enzymes glycerol 3-phosphate dehydrogenase (G3PDH), fatty acid synthetase (FAS) and lipoprotein lipase (LPL) were studied in perirenal (PR) and subcutaneous (SO adipose depots of 28 male lambs of Rasa Aragonesa Spanish breed. Three groups of animals were slaughtered at: 32 (s.d. 6) (no. = 10), 89 (s.d. 8) (no. = 10) and 120 (s.d. 8) (no. = 8) days of age. A significant increase in the quantity of fat was observed as the age of the lambs increased (P < 0·001). Fat deposition was higher between 89 and 120 days of age. The number of adipocytes in the PR depot did not change but hypertrophy in this depot continued during the whole period studied (P < 0·001). In the SC depot a significant increase in adipocyte volume was only found between 89 and 120 days of age (P < 0·001). The increase in G3PDH activity (which estimates fatty acid esterification) and FAS activity (which estimates fatty acid synthesis) was greater in the final phase of the study. Besides, LPL enzyme activity (which estimates the uptake of plasma fatty acids) increased between 32 and 89 days of age in both depots and between 89 and 120 days in PR depot (P < 0·001).

Influence of sex on cellularity and lipogenic enzymes of Spanish lamb breeds (Lacha and Rasa Aragonesa)

The effect of sex on the size and number of adipocytes and on the lipogenic enzyme activity in different fat depots in Lacha (L) and Rasa Aragonesa (RA) lambs was studied. Male and female L lambs were fed on ewe milk and were slaughtered at 25 and 24 days of age corresponding to 11·4 and 10·9 kg live weight (UN), respectively. Male and female RA lambs were weaned at 58 days (16·0 kg LW) and were then given concentrates and barley straw until slaughtered at 89 and 91 days of age corresponding to 24·5 and 23·1 kg LW, respectively. A number of parameters were studied in omental (OM), mesenteric (MES) and kidney knob and channel fat (KKCF) depots including the amount of fat, the number and size of adipocytes and the activity of the following enzymes: glycerol 3-phosphate dehydrogenase (G3PDH), fatty acid synthetase (FAS), glucose 6-phosphate dehydrogenase (G6PDH) and NADPmalate dehydrogenase (MD). In subcutaneous (SC) and intermuscular (IM) depots, all the former parameters except the adipocyte number were studied. Females of both breeds had higher amounts of adipose tissue than males in the internal fat depots (P < 0·05) as well as larger adipocytes, mainly in the KKCF (P < 0·05 andP < 0·001 for L and RA lambs, respectively) and OM (P < 0·05 in the RA lambs) depots. There were no differences between sexes in the number of adipocytes. The activity of the G3PDH enzyme was higher in females than in males in OM and SC depots (P < 0·01) in L lambs, and in KKCF, IM (P < 0·05), OM and MES (P < 0·001) depots in RA lambs. Thus, the sex effect on adiposity in both breeds studied involved a greater fattening of the females which was consistent with a greater hypertrophy and a higher G3PDH activity.