Effects of glucocorticoid hormones on lipid-synthetic enzymes from different adipose tissue regions and from liver

Abstract

The regional diversity of adipose tissue is dramatically accentuated in states of glucocorticoid excess, in which certain fat depots expand, while others contract. We have studied the molecular basis of this redistribution by determining the activity of fatty acid synthetase and enzymes catalyzing di- and tri-acylglycerol synthesis, in subcellular fractions from four adipose depots of rats injected with dexamethasone and from interscapular and epididymal adipocyte precursors after addition of either dexamethasone or corticosterone to confluent monolayers in secondary culture. Subcellular fractions from cervical and interscapular adipose tissue, as well as from cultured interscapular precursors, revealed a general increase in specific enzyme activity. The opposite trend was observed for retroperitoneal and epididymal fat tissue, as well as cultured epididymal precursors. Fatty acid synthetase and cytosolic phosphatidate phosphohydrolase appeared to be most responsive. The findings in culture indicate that the regional effects of glucocorticoids are partly independent of other circulating or neural factors. Injections of dexamethasone led to significantly enhanced specific activity of all the lipid-synthetic enzymes assayed in subcellular fractions from liver. Differences in hormonal influences between liver and certain fat tissue regions represent tissue specificity. In addition, the diverse effects of glucocorticoids on various adipose tissue depots indicate regional or "intratissue" specificity.

Liver-specific loss of lipin-1-mediated phosphatidic acid phosphatase activity does not mitigate intrahepatic TG accumulation in mice

“…However, hepatic lipin 1 expression is robustly induced by a variety of metabolic stimuli that signal the need for increased PAP activity including fasting ( 14,23 ), glucocorticoids and cAMP signaling ( 14,23 ), experimental ethanol administration ( 24 ), sterols ( 25 ), and liver regeneration ( 26 ). These fi ndings are congruent with older data, generated before the cloning of lipins, that detected increased PAP activity in response to these stimuli (27)(28)(29)(30). Because lipin 1 has the highest intrinsic PAP activity of the lipin family proteins ( 4 ), the induction of lipin 1 expression by these stimuli fi ts with this being an adaptive response to augment the hepatic capacity for TG synthesis in response to increased supply of fatty acids.…”

Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome

“…Accordingly, VLDL production rates are elevated in Cushing's syndrome, and since VLDL clearance is unaltered this accounts for increased circulating VLDL and atherogenic LDL levels (Taskinen et al 1983). Additionally, glucocorticoids act to increase the activity of a number of enzymes involved in hepatic TAG synthesis (Bates & Saggerson 1979, Lau & Roncari 1983, Pittner et al 1985; see Fig. 2).…”

Effect of Chronic Modification of Diet Fat and Cholesterol during Gestation on Plasma Hormones and Hepatic Enzyme Activities in Rat Fetus

“…In contrast, Naseem et al [6,7] have given evidence of a lasting reduced HMGCoA reductase activity in the progeny of rats fed high fat and cholesterol diets in preg nancy [6,7], The difference of these to present and earlier studies [34,35] may be the use of 40% diet fat. Similar very high fat diets have been found to cause increased pla cental and reduced fetal weights [unpub lished observations], and fetal ketonemia and altered placental amino acid and glucose transfer [36], Glucocorticoids have a well-known abil ity to induce TAT and FAS in adult rat liver [37,38] and cystathionase in fetal liver [15], In the adult rat, hepatic cystathionase is in sensitive to glucocorticoid, but is suppressed by T4. No relationship between the elevated corticosterone level (table I) and an induc tion of TAT or cystathionase (table II) was present.…”