Key result
In human adipose tissue cultures, insulin increased LPL synthesis approximately 7-fold, while adding dexamethasone increased LPL activity approximately 8-fold by inhibiting degradation.
Why the study?
Do insulin and dexamethasone modulate lipoprotein lipase synthesis and degradation in human adipose tissue?
Do insulin and dexamethasone modulate lipoprotein lipase synthesis and degradation in human adipose tissue?
In human adipose tissue, insulin is essential for maintaining LPL synthesis, whereas glucocorticoids like cortisol regulate LPL post-translationally by inhibiting its degradation.
Answers are grounded in this paper and cite their sources.
These ex vivo findings warrant in vivo validation; leaves open clinical relevance for insulin or glucocorticoid effects on LPL.
The mechanisms by which insulin and glucocorticoids modulate lipoprotein lipase (LPL) synthesis and degradation were examined in human adipose tissue fragments maintained in organ culture. Tissue fragments were cultured for 7 days in serum-free medium supplemented with or without insulin (7 nM) and with or without dexamethasone (30 nM), a synthetic glucocorticoid. Responses of LPL activity to both insulin and dexamethasone were obtained at doses within the physiological range. At a maximal dose, insulin increased heparin-releasable and total LPL activity (approximately 7-fold) by specifically increasing the rate of LPL synthesis (approximately 5-fold) determined by pulse labeling with [35S]methionine and [35S]cysteine and immunoprecipitation. Dexamethasone added in the presence of insulin increased heparin-releasable and total LPL activity approximately 8-fold but did not alter rates of LPL synthesis compared with insulin alone. Pulse-chase studies showed that the rate of LPL degradation was markedly slowed in the presence of dexamethasone plus insulin compared with insulin alone. These data suggest that, in human adipose tissue, insulin is essential for maintaining rates of LPL synthesis and that cortisol may play a key role in regulating human adipose tissue LPL at the posttranslational level by inhibiting the degradation of newly synthesized LPL.
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Appel et al. (1992) studied this question. Insulin and dexamethasone vs. Without insulin and without dexamethasone / insulin alone was evaluated on Lipoprotein lipase (LPL) synthesis and degradation. In human adipose tissue cultures, insulin increased LPL synthesis approximately 7-fold, while adding dexamethasone increased LPL activity approximately 8-fold by inhibiting degradation.
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