ABSTRACT: HintergrundDie Akkumulation hepatozellulärer Lipidtropfen als Ausdruck einer Steatose ist die häufigste Lebererkrankung in den westlichen
Industrieländern. Die Oberfläche von Lipidtropfen wird durch amphiphile Proteine der PAT-Familie (Perilipin, Adipophilin und TIP47) stabilisiert. Wir konnten kürzlich zeigen, dass PAT-Proteine in der Leber differenziell exprimiert werden.
MethodenDie Effekte einer Lipidtropfeninduktion mit Oleat und einer siRNA-vermittelten Herunterregulation wurden mittels Immunfluoreszenzmikroskopie,
Immunblot und funktionellen Tests untersucht.
ErgebnisseWährend in steatotischen Hepatozyten Perilipin, Adipophilin und nur in geringem Umfang auch TIP47 Lipidtropfen ummanteln,
sind in hepatozellulären Zellkulturlinien nach Oleatbehandlung nur Adipophilin und TIP47 nachweisbar, nicht jedoch Perilipin.
Auch nach Herunterregulation von Adipophilin oder TIP47 wird Perilipin nicht induziert.
SchlussfolgerungGängige Steatose-Zellkulturmodelle unterscheiden sich gegenüber humaner hepatozellulärer Steatose in vivo. Möglicherweise
spielt Perilipin eine Rolle bei der Langzeitspeicherung von Fetten, die in Zellkulturmodellen nur partiell widergespiegelt
BackgroundThe accumulation of hepatocellular lipid droplets, referred to as steatosis, is the most frequent liver pathology in western
industrial countries. The surface of lipid droplets is stabilized by amphiphilic proteins of the PAT family (perilipin, adipophilin,
TIP47). We recently showed that PAT proteins are differentially expressed in liver.
MethodsThe effects of lipid droplet induction with oleate and of siRNA-mediated downregulation of PAT proteins were evaluated using
immunofluorescence microscopy, immunoblot and functional assays.
ResultsWhereas perilipin, adipophilin and (in only minor amounts) also TIP47 coat lipid droplets in steatotic hepatocytes, adipophilin
and TIP47, but not perilipin, are detectable in hepatocellular cell cultures. Likewise, perilipin is not induced after downregulation
of adipophilin and TIP47.
ConclusionsCommon cell culture models show specific differences to human hepatocyte steatosis in vivo. Perilipin may play a role in the long-term storage of fat, which may be only partially reflected by cell culture models.
KeywordsFatty liver-Lipid droplets-Steatosis-PAT proteins
Der Pathologe 05/2012; 31:126-131. · 0.67 Impact Factor
ABSTRACT: AIMS: Lipid droplets (LDs) are dynamic storage compartments for energy-rich fats that are nearly ubiquitously present in eukaryotic cells, exerting tissue-specific functions in metabolically active cell types, and are increased in conditions following cellular damage or lipid overload. The LD-cytoplasm interface is stabilized by amphiphilic proteins of the PAT/perilipin family (perilipin/perilipin-1, adipophilin/perilipin-2, and TIP47/perilipin-3). We evaluated the value of adipophilin immunohistochemistry for the diagnosis of diseases associated with LD accumulation. METHODS AND RESULTS: In human tissues, adipophilin-positive LDs were especially prominent in steroidogenic cells of the adrenal gland, testis, and ovary, in hepatocytes and hepatic stellate cells, in cardiac, striated and smooth myocytes, in lactating mammary gland epithelial cells, and in plurivacuolar adipocytes. Variable amounts of adipophilin-positive LDs were also detected almost ubiquitously in epithelial cells of the gastrointestinal tract and skin. In diseases associated with lipid storage, adipophilin was strongly expressed in lipid-laden macrophages in atherosclerosis, in cardiomyopathies, kidney diseases, hepatocyte steatosis, colon ischaemia, and at the border of organ infarcts. CONCLUSIONS: Adipophilin immunohistochemistry visualizes small LDs in tissues under physiological and disease conditions that are not visible by conventional light microscopy. Immunohistology for adipophilin may facilitate histomorphological diagnosis of diseases and definition of the extent of metabolic dysregulation, such as in organ infarcts, cardiomyopathies, kidney diseases, and microvesicular steatosis.
Histopathology 01/2012; · 3.08 Impact Factor
ABSTRACT: The accumulation of hepatocellular lipid droplets, referred to as steatosis, is the most frequent liver pathology in western industrial countries. The surface of lipid droplets is stabilized by amphiphilic proteins of the PAT family (perilipin, adipophilin, TIP47). We recently showed that PAT proteins are differentially expressed in liver.
The effects of lipid droplet induction with oleate and of siRNA-mediated downregulation of PAT proteins were evaluated using immunofluorescence microscopy, immunoblot and functional assays.
Whereas perilipin, adipophilin and (in only minor amounts) also TIP47 coat lipid droplets in steatotic hepatocytes, adipophilin and TIP47, but not perilipin, are detectable in hepatocellular cell cultures. Likewise, perilipin is not induced after downregulation of adipophilin and TIP47.
Common cell culture models show specific differences to human hepatocyte steatosis in vivo. Perilipin may play a role in the long-term storage of fat, which may be only partially reflected by cell culture models.
Der Pathologe 10/2010; 31 Suppl 2:126-31. · 0.67 Impact Factor
ABSTRACT: Cysts of the iris are uncommon and most of them occur secondarily after surgery or penetrating injury. The minority of the iris cysts is primary without a reasonable cause. They are classified into the more common pigment epithelial cysts and the rare cysts of iris stroma ("intrastromal cysts"). These intrastromal iris cysts are generally diagnosed in children and often cause symptoms such as a decrease of visual acuity because of ingrowth into the optical axis. A diagnosis of stromal cysts in adults is very rare. Most of these patients remain without any symptoms and do not need treatment. The cellular origin is so far unknown. Mesoderm, neuroectoderm and surface ectoderm have been discussed in this context.
Two patients with primary intrastromal iris cysts are presented, a 5-year-old boy and a 65-year-old woman. In both cases, the cyst affected the optical axis and was removed by sector iridectomy. In histological and electron-microscopic examinations both cysts presented a typical epithelial structure. Immunohistochemical examination revealed positivity for epithelial markers and negativity for mesenchymal and neuroectodermal markers.
Primary intrastromal iris cysts can occur in advanced age and may cause symptoms due to progressive growth. The cellular origin of primary intrastromal iris cysts is controversially discussed in the literature. On electron microscopy and immunohistochemistry, the iris cysts presented here showed characteristic features of surface ectodermal origin.
Klinische Monatsblätter für Augenheilkunde 05/2010; 227(5):425-9. · 0.51 Impact Factor
ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases in Western industrialized countries with dramatically rising incidence. The diagnosis of NAFLD requires the existence of steatosis in the absence of significant alcohol consumption. In cases of relevant inflammation pathogenetically linked to steatosis, it is termed non-alcoholic steatohepatitis (NASH). While pure steatosis represents a relatively harmless and rapidly reversible condition without a significant tendency to progression, NASH carries a significant morbidity and progression risk. Noninvasive methods neither reliably establish the diagnosis nor define the extent of disease in NASH, making histopathology the diagnostic gold standard. Since current therapeutic options in NASH are limited, indication for biopsy is made in the clinical context, predominantly in unclear clinical constellations, prior to invasive measures, for follow-up purposes and in the context of clinical studies. Histological hallmarks of NASH are steatosis, hepatocellular ballooning (with and without Mallory-Denk bodies), necroinflammation, and progressing disease a characteristic with perisinusoidal fibrosis. For semiquantitative assessment of necroinflammation (grading) and fibrosis (staging), a score has recently been implemented. Although histology does not reliably distinguish alcoholic steatohepatitis/alcoholic fatty liver disease from NASH/NAFLD, it may give valuable hints. NASH has a tendency for more steatosis, the so-called glycogenated nuclei, and less necroinflammatory activity. Future development of biopsy diagnosis will be coupled to the development of differential systemic therapeutic approaches. Especially in the context of clinical studies, detailed histological evaluation should be considered for the detection of predictive parameters.
Digestive Diseases. 08/1970; 28(1):197-202.