Absence of perilipin results in leanness and reverses obesity in Leprdb/db mice

Martı́nez-Botas, Javier; Anderson, John B.; Tessier, Darin; Lapillonne, Alexandre; Chang, Benny Hung-Junn; Quast, Michael J.; Gorenstein, David G.; Chen, Kuang-Hua; Chan, Lawrence

doi:10.1038/82630

Cited by 541 publications

(482 citation statements)

References 16 publications

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“…Activation of, or overexpression of, HSL prevents TG accumulation in adipocytes (Sztalryd et al, 1995). Perilipins, which are phosphoproteins coating the surfaces of lipid droplets of adipocytes, have been postulated to modulate HSL activity (Martinez-Botas et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte

Choi

Ahn²,

Kim³

et al. 2006

Exp Mol Med

148

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Berberine (BBR), an isoquinoline alkaloid, has a wide range of pharmacological effects, yet its exact mechanism is unknown. In order to understand the anti-adipogenic effect of BBR, we studied the change of expression of several adipogenic enzymes of 3T3-L1 cells by BBR treatment. First, we measured the change of leptin and glycerol in the medium of 3T3-L1 cells treated with 1 µM, 5 µM and 10 µM concentrations of BBR. We also measured the changes of adipogenic and lipolytic factors of 3T3-L1. In 3T3-L1 cells, both leptin and adipogenic factors (SREBP-1c, C/EBP-, PPAR-γ, fatty acid synthase, acetyl-CoA carboxylase, acyl-CoA synthase and lipoprotein lipase) were reduced by BBR treatment. Glycerol secretion was increased, whereas expression of lipolytic enzymes (hormone-sensitive lipase and perilipin) mRNA was slightly decreased. Next, we measured the change of inflammation markers of 3T3-L1 cells by BBR treatment. This resulted in the down-regulation of mRNA level of inflammation markers such as TNF-α, IL-6, Creactive protein and haptoglobin. Taken together, our data shows that BBR has both anti-adipogenic and anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect seems to be due to the down-regulation of adipogenic enzymes and transcription factors.

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Section: Introductionmentioning

confidence: 99%

Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte

Choi

Ahn²,

Kim³

et al. 2006

Exp Mol Med

148

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“…Studies in perilipin knockout mice have established an important role for perilipins in regulating lipolysis in adipocytes, and hence, controlling the mass of triacylglycerol deposited in adipose tissue (10,11). The mechanisms by which perilipins maintain control of adipocyte triacylglycerol metabolism are poorly understood, although recent mutagenesis studies have identified structural motifs important to perilipin function in triacylglycerol storage and lipolysis (12)(13)(14)(15)(16)).…”

mentioning

confidence: 99%

Perilipin A Mediates the Reversible Binding of CGI-58 to Lipid Droplets in 3T3-L1 Adipocytes

Subramanian

Rothenberg

Gómez

et al. 2004

Journal of Biological Chemistry

275

290

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Perilipins, the major structural proteins coating the surfaces of mature lipid droplets of adipocytes, play an important role in the regulation of triacylglycerol storage and hydrolysis. We have used proteomic analysis to identify CGI-58, a member of the ␣/␤-hydrolase fold family of enzymes, as a component of lipid droplets of 3T3-L1 adipocytes. CGI-58 mRNA is highly expressed in adipose tissue and testes, tissues that also express perilipins, and at lower levels in liver, skin, kidney, and heart. Both endogenous CGI-58 and an ectopic CGI-58-GFP chimera show diffuse cytoplasmic localization in 3T3-L1 preadipocytes, but localize almost exclusively to the surfaces of lipid droplets in differentiated 3T3-L1 adipocytes. The localization of endogenous CGI-58 was investigated in 3T3-L1 cells stably expressing mutated forms of perilipin using microscopy. CGI-58 binds to lipid droplets coated with perilipin A or mutated forms of perilipin with an intact C-terminal sequence from amino acid 382 to 429, but not to lipid droplets coated with perilipin B or mutated perilipin A lacking this sequence. Immunoprecipitation studies confirmed these findings, but also showed co-precipitation of perilipin B and CGI-58. Remarkably, activation of cAMP-dependent protein kinase by the incubation of 3T3-L1 adipocytes with isoproterenol and isobutylmethylxanthine disperses CGI-58 from the surfaces of lipid droplets to a cytoplasmic distribution. This shift in subcellular localization can be reversed by the addition of propanolol to the culture medium. Thus, CGI-58 binds to perilipin Acoated lipid droplets in a manner that is dependent upon the metabolic status of the adipocyte and the activity of cAMP-dependent protein kinase.Lipid droplets, organelles that store neutral lipids, are found in nearly all types of eukaryotic cells. The most highly studied lipid droplet-associated proteins are members of the PAT 1 (for perilipin, adipophilin (also called adipose differentiation-related protein or ADRP), and TIP47) family of proteins (1) that includes perilipin, adipophilin, TIP47, and a related but structurally divergent protein, S3-12 (2, 3). Three protein isoforms of perilipins, named perilipins A, B, and C, are translated from alternatively spliced forms of mRNA. Perilipin A and S3-12 localize to lipid droplets in adipocytes (3-5), where they are the most abundant structural proteins of large mature and small nascent lipid droplets, respectively. In contrast, most other types of cells have small lipid droplets covered with adipophilin (6, 7) and TIP47 (1, 8, 9). Perilipins A and C, and adipophilin, coat the lipid droplets of steroidogenic cells (6) that store cholesterol ester precursors for steroid hormone synthesis.The members of the PAT family comprise the major structural proteins of lipid droplets. Studies in perilipin knockout mice have established an important role for perilipins in regulating lipolysis in adipocytes, and hence, controlling the mass of triacylglycerol deposited in adipose tissue (10, 11). The mechanisms by which per...

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“…Das Vorhandensein der PAT Proteine an Lipidtropfen scheint für Li pidtropfen essenziell zu sein, da der Ver lust von Adipophilin und Perilipin im Mausmodell organspezifisch eine drasti sche Reduktion der Lipidtropfen bewirkt [3,11]. Offenbar können verschiedene PAT Proteine sich nur bedingt gegensei tig kompensieren.…”

Section: Diskussionunclassified