Cytoplasmic receptor-interacting protein 140 (RIP140) interacts with perilipin to regulate lipolysis

Abstract

Receptor-interacting protein 140 (RIP140) is abundantly expressed in mature adipocyte and modulates gene expression involved in lipid and glucose metabolism. Protein kinase C epsilon and protein arginine methyltransferase 1 can sequentially stimulate RIP140 phosphorylation and then methylation, thereby promoting its export to the cytoplasm. Here we report a lipid signal triggering cytoplasmic accumulation of RIP140, and a new functional role for cytoplasmic RIP140 in adipocyte to regulate lipolysis. Increased lipid content, particularly an elevation in diacylglycerol levels, promotes RIP140 cytoplasmic accumulation and increased association with lipid droplets (LDs) by its direct interaction with perilipin. By interacting with RIP140, perilipin more efficiently recruits hormone-sensitive lipase (HSL) to LDs and enhances adipose triglyceride lipase (ATGL) forming complex with CGI-58, an activator of ATGL. Consequentially, HSL can more readily access its substrates, and ATGL is activated, ultimately enhancing lipolysis. In adipocytes, blocking cytoplasmic RIP140 accumulation reduces basal and isoproterenol-stimulated lipolysis and the pro-inflammatory potential of their conditioned media (i.e. activating NF-κB and inflammatory genes in macrophages). These results show that in adipocytes with high lipid contents, RIP140 increasingly accumulates in the cytoplasm and enhances triglyceride catabolism by directly interacting with perilipin. The study suggests that reducing nuclear export of RIP140 might be a useful means of controlling adipocyte lipolysis.

Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses

“…ER microsomal fractions were then isolated as previously described (Ho et al, 2011). ER vesicles were then analyzed by a calcium uptake assay with 45CaCl2 as the tracer of calcium uptake, as previously described (Borge and Wolf, 2003).…”

Genome‐wide association analysis identifies the genetic basis of fat deposition in the tails of sheep (Ovis aries)

“…The other two variants on chromosome 1, rs402445895 and rs416201901, are within the nuclear receptor interacting protein 1 gene (NRIP1, also known as RIP140), which encodes a nuclear protein also known as receptor-interacting protein 140 (RIP140). RIP140 is widely expressed and plays an important role in regulating lipid and glucose metabolism (Leonardsson et al 2004;Ho et al 2011;Hochberg et al 2015). However, no genes that affect fat development have been mapped in the genomic region OARX: 88-89 Mb using the reference genomes of sheep and other mammals.…”

Combined Gene and Protein Expression of Hormone-Sensitive Lipase and Adipose Triglyceride Lipase, Mitochondrial Content, and Adipocyte Size in Subcutaneous and Visceral Adipose Tissue of Morbidly Obese Men

“…Our results are informative with respect to enzymes involved in basal lipolysis, though provide no information on the postprandial state. We did not assess the expression levels of potential co-activators of enzymes involved in lipolysis, such as perilipin, RIP140, and CGI-58, which have been implicated in the regulation of ATGL activity [39][40][41].…”