PLIN2, the major perilipin regulated during sebocyte differentiation, controls sebaceous lipid accumulation in vitro and sebaceous gland size in vivo

Abstract

Background Lipid synthesis and storage are accomplished by lipid droplets (LDs). The perilipin family of LD-associated proteins, comprising 5 members (PLIN1-PLIN5), has been well characterized in adipocytes but not in sebocytes, epithelial cells in which LD formation is a key feature of the cellular differentiation. Methods Perilipin expression in the sebaceous gland cell line SZ95 and in human sebaceous glands was studied by qRT-PCR, Western blots, and immunohistochemistry. Lipid accumulation was evaluated by Nile red staining and mass spectrometry. Results PLIN2 and PLIN3 are the most abundant perilipins in undifferentiated sebocytes. Induction of lipogenesis by linoleic acid (LA) resulted in increased transcript levels of all perilipins except for PLIN3 and in a time-dependent increase of PLIN2 protein. Nile red staining revealed that siRNA-mediated downregulation of PLIN2 significantly impaired basal and LA-induced lipid accumulation. Mass spectrometry revealed PLIN2 deficiency to cause a reduction in the amount of several specific lipid fractions, including di- and triacyl-glycerol esters, phosphatidylcholine lipids, and ceramides in sebocytes under basal conditions. In contrast, PLIN2 downregulation exerted a statistically significant inhibitory effect only on the accumulation of specific LA-induced triglycerides. PLIN2-deficient mice showed normal morphology of sebaceous glands. However, their sebaceous glands were significantly reduced in size and showed less cell proliferation. Conclusions PLIN2 is the major perilipin regulated during sebocyte differentiation in vitro. PLIN2 is also important for sebaceous lipid accumulation in vitro and regulates sebaceous gland size in vivo. General significance Our study provides the first systematic analysis of LD-associated proteins in sebocytes.

Perilipin 3 modulates specific lipogenic pathways in SZ95 sebocytes

“…We showed previously that PLIN2 expression is regulated during sebocyte differentiation and is important for lipid accumulation in vitro and for regulating SG size in vivo (18). PLIN3 expression was higher than that of PLIN2, but did not change as sebocytes differentiate (18).…”

“…We showed previously that PLIN2 expression is regulated during sebocyte differentiation and is important for lipid accumulation in vitro and for regulating SG size in vivo (18). PLIN3 expression was higher than that of PLIN2, but did not change as sebocytes differentiate (18). Initially identified as a protein involved in the recycling of the mannose 6-phosphate receptor and termed TIP47 for 'tail-interacting protein of 47 kDa (19), PLIN3 was localized by Wolins and colleagues to nascent LDs (20).…”

Pulmonary Administration of GW0742, a High-Affinity Peroxisome Proliferator-Activated Receptor Agonist, Repairs Collapsed Alveoli in an Elastase-Induced Mouse Model of Emphysema

“…Stimulation of PPARβ/δ affects many cellular process, including glucose metabolism, fatty acid metabolism, and keratinocyte, 19,20) adipocyte and sebocyte differentiation. 21) We focused on the ability of PPARβ/δ activation to induce differentiation. It has also been reported that mice have epithelial stem/ progenitor cells, as do humans.…”

Primary sebocytes and sebaceous gland cell lines for studying sebaceous lipogenesis and sebaceous gland diseases

“…Antimicrobial role of sebum (innate immunity) SZ95 [58][59][60][61][62][63] SEB-1 [64] Expression and regulation of sebocyte lipid droplet-associated proteins SZ95 [50,[65][66][67] Seb-E6E7 [50] Mechanisms of IGF-1-mediated stimulation of sebaceous lipogenesis SEB-1 [68,69] SZ95 [70] Actions of peroxisome proliferator-activated receptors in sebocytes SEB-1 [71] SZ95 [72][73][74] Actions of endocannabinoids in sebocytes SZ95 [75] Mechanisms of retinoid-mediated inhibition of sebaceous lipogenesis SZ95 [39,76] SEB-1 [77][78][79] Expression of steroidogenesis-related enzymes and regulation of local androgen synthesis SZ95 [40,80] SEB-1 [41] SEBO662 [44] Mechanisms of apoptosis in sebocytes SZ95 [81] SEB-1 [41] Cutaneous functions of the vitamin D system SZ95 [82,83] Regulation of sebaceous lipogenesis by microRNAs SZ95 [49] Neuropeptide synthesis and their action on sebocytes SZ95 [84,85] molecular and cellular processes underlying sebaceous lipogenesis and their perturbation in SG diseases (Table 1). Recent examples of fields pushed forward by employing immortalized human SG cell lines include the analysis of sebocyte adipokines, [48] the identification of microRNAs associated with sebaceous differentiation, [49] and the study of the proteins associated with cytoplasmic SG lipi...…”