Although neutral lipid storage droplets are ubiquitous in eukaryotic cells, very little is known about how their synthesis and turnover are controlled. Adipocyte differentiation-related protein (ADRP; also known as adipophilin) is found on the surface of lipid droplets in most mammalian cell types. To learn how ADRP affects lipid storage, we stably expressed the protein in human embryonic kidney 293 (HEK 293) cells, which express little endogenous ADRP. As expected, ADRP was targeted to the surface of lipid droplets and caused an increase in triacylglycerol (TAG) mass under both basal and oleate-supplemented conditions. At least part of the increased mass resulted from a 50% decrease in the rate of TAG hydrolysis in ADRPexpressing cells. Furthermore, ADRP expression increased the fraction of total cellular TAG that was stored in lipid droplets. ADRP expression induced a striking decrease in the association of adipose triglyceride lipase (ATGL) and mannose-6-phosphate receptor tail-interacting protein of 47 kDa with lipid droplets and also decreased the lipid droplet association of several other unknown proteins. Transient expression of ADRP in two other cell lines also reduced the lipid droplet association of catalytically inactive ATGL. We conclude that the reduced lipid droplet association of ATGL and/or other lipases may explain the decrease in TAG turnover observed in ADRP-expressing HEK 293 cells. Eukaryotes store lipid in cytosolic lipid droplets, which consist of neutral lipid cores surrounded by phospholipid monolayers (1-3). In mammals, lipid droplets are most abundant in adipose tissue, where stored triacylglycerol (TAG) provides the primary energy reserve for the organism. Lipid droplets in steroidogenic cells contain cholesteryl esters used in the synthesis of steroid hormones. Most other mammalian cells contain smaller lipid droplets, whose function remains unclear. They may serve as local energy reserves or sources of lipid for membrane synthesis. Furthermore, they may protect cells from the harmful effects of excess lipid accumulation by sequestering toxic lipid species away from pathways that lead to cell death (4, 5).Mechanisms controlling the synthesis and turnover of lipid droplets are only partially understood. According to one model of lipid droplet biogenesis, newly synthesized neutral lipids accumulate inside the endoplasmic reticulum membrane, forming a disk that eventually buds into the cytoplasm surrounded by an endoplasmic reticulumderived phospholipid monolayer (2, 6). Conversely, lipid droplet turnover occurs via the hydrolysis of stored neutral lipids by cytosolic lipases. Much of what we know about the regulation of lipolysis stems from studies in adipocytes. In response to hormone stimulation, protein kinase A phosphorylates two key substrates: hormone-sensitive lipase (HSL) (7) and perilipins (8, 9). Phosphorylation of HSL stimulates both its activity and its association with lipid droplets, in a manner that depends on perilipins.Perilipins regulate TAG hydrolysis in two...
This study develops and demonstrates a theoretical framework and corresponding methodology to link variables at the culture level to the individual level and, then, to specific outcome variables. The authors argue that in order to advance theory about culture's influence on communication, researchers must begin to examine how culture affects individual level (psychological) processes and, subsequently, how these processes affect communication. The image of self, referred to as self-construal, is an ideal candidate to perform the role of linking culture to behavior. The self is shaped by cultural forces and affects many, if not all, communication behaviors. The proposed strategy is applied in the test of a path-analytic model linking cultural collectivism with interdependent self-construals and, ultimately, high-context communication. The discussion includes implications for theory development and possible applications to further research.
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