PubMed · 9622289
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M Cucuianu. 1998. Hyperlipidemia and serum complement.. https://doi.org/10.1016/s0021-9150(97)00299-2
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In vitro growth hormone (GH) stimulation of Janus kinase 2 (Jak2) tyrosine phosphorylation and activation has been detected in rat adipocytes where GH exerts both chronic diabetogenic and acute insulin-like effects but not in adipocytes where only chronic diabetogenic effects are exerted. The 95 kDa transcription factor Stat5, which is tyrosine phosphorylated in response to GH in both cases, is here identified as the 5A-isoform. Stat5B was not tyrosine phosphorylated in response to GH in adipocytes but subject to a gel supershift indicating regulation by serine and/or threonine phosphorylation. The differential tyrosine phosphorylation of these proteins suggests involvement of a kinase other than Jak2 in Stat5A activation. However, in adipocytes where GH exerts both diabetogenic and insulin-like effects, and both Jak2 and Stat5A were activated, their phosphorylation kinetics and downregulation of tyrosine phosphorylation were almost identical. We conclude that Stat5A is important for the diabetogenic actions of GH and that Jak2 still is the most probable candidate kinase for Stat5A in primary adipocytes.
The concept that selective transfer of high density lipoprotein (HDL)-derived cholesteryl esters (CE) does not require lipoprotein internalization has been challenged recently by evidence that implicates HDL recycling during the selective uptake process. This has prompted us to examine the role of the low density lipoprotein receptor-related protein (LRP) in selective uptake. LRP is an endocytic receptor for lipoprotein lipase (LpL) and apolipoprotein E (apoE) ligands that are able to mediate selective uptake. We report that molecules that interfere with ligand binding to LRP, such as the receptor-associated protein (RAP), suramin, alpha(2)-macroglobulin, or lactoferrin, inhibit HDL-CE selective uptake by human primary adipocytes and SW872 liposarcoma cells by 35-50%. This partial inhibition of selective uptake from total HDL was not due to preferential inhibition of the HDL(2) or HDL(3) subfractions. Selective uptake by the scavenger receptor BI was not inhibited by RAP, excluding its involvement. Furthermore, in SW872 cells in which LRP was reduced to 14% of control levels by stable antisense expression, selective uptake was attenuated by at least 33%, confirming a role for LRP in this process. RAP, alpha(2)-macroglobulin, lactoferrin, and suramin (individually or in paired combinations) also attenuated selective uptake of HDL-CE by primary human adipocytes by about 40%. On the other hand, human skin fibroblasts express LRP abundantly but lack the capacity for selective uptake, demonstrating that other molecules are required. In SW872 cells, exogenous apoE or LpL can facilitate selective uptake but only the apoE-enhanced uptake can be inhibited by RAP, implicating apoE as a likely co-mediator. We discuss the possible mechanisms by which the endocytic receptor, LRP, can mediate selective uptake.
White adipose tissue and liver are important angiotensinogen (AGT) production sites. Until now, plasma AGT was considered to be a reflection of hepatic production. Because plasma AGT concentration has been reported to correlate with blood pressure, and to be associated with body mass index, we investigated whether adipose AGT is released locally and into the blood stream. For this purpose, we have generated transgenic mice either in which adipose AGT is overexpressed or in which AGT expression is restricted to adipose tissue. This was achieved by the use of the aP2 adipocyte-specific promoter driving the expression of rat agt cDNA in both wild-type and hypotensive AGT-deficient mice. Our results show that in both genotypes, targeted expression of AGT in adipose tissue increases fat mass. Mice whose AGT expression is restricted to adipose tissue have AGT circulating in the blood stream, are normotensive, and exhibit restored renal function compared with AGT-deficient mice. Moreover, mice that overexpress adipose AGT have increased levels of circulating AGT, compared with wild-type mice, and are hypertensive. These animal models demonstrate that AGT produced by adipose tissue plays a role in both local adipose tissue development and in the endocrine system, which supports a role of adipose AGT in hypertensive obese patients.