Dataset Information

Nuclear hormone-sensitive lipase controls adipocyte function

ABSTRACT: Hormone-sensitive lipase (HSL) is a neutral lipase which hydrolyses fat stored as triacylglycerols in adipocyte lipid droplets. Its activity is under the control of hormones and neurotransmitters through protein kinase (PK)-mediated phosphorylation. Here we show that HSL is expressed in the nucleus where it controls the biological functions of the adipocyte. Gene editing reveals that the development of adipose tissue in vivo relies on nuclear HSL. In the nucleus, HSL interacts with a network of proteins involved in transcriptional and post-transcriptional events. TGFβ activation of SMAD3 promotes HSL nuclear accumulation whereas PKA-mediated phosphorylation induces HSL nuclear export. HSL nuclear content is increased in obese mouse adipose tissue whereas expression of a catalytically inactive nuclear HSL impairs glucose homeostasis. These findings reveal that nuclear HSL is essential for the maintenance of adipocyte function. HSL integrates signals from the TGFβ and catecholamine signaling pathways and controls adipocyte mitochondrial oxidative activity.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Preadipocyte

SUBMITTER: Karima Chaoui

LAB HEAD: Dominique Langin

PROVIDER: PXD043860 | Pride | 2026-01-30

REPOSITORIES: pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 9

Similar Datasets

Project description:Abstract Background In obesity, adipose tissue undergoes a remodeling process characterized by increased adipocyte size (hypertrophia) and number (hyperplasia). The individual ability to tip the balance toward the hyperplastic growth, with recruitment of new fat cells through adipogenesis, seems to be critical for a healthy adipose tissue expansion, as opposed to the development of inflammation and detrimental metabolic consequences. However, the molecular mechanisms underlying this fine-tuned regulation are far from being understood. Methods We analyzed by mass spectrometry-based proteomics visceral white adipose tissue (vWAT) samples collected from C57BL6 mice fed with a HFD for 8 weeks. A subset of these mice, called low responders (LowR HFD), showed a low susceptibility to the onset of adipose tissue inflammation, as opposed to their HFD counterpart. We identified the discriminants between LowR HFD and HFD vWAT samples and explored their function in Adipose Derived human Mesenchymal Stem Cells (AD-hMSCs) differentiated to adipocytes. Results We quantified 6051 proteins. Among the candidates that most differentiate LowR HFD from HFD vWAT, we found proteins involved in adipocyte function, including adiponectin and hormone sensitive lipase, suggesting that adipocyte differentiation is enhanced in LowR HFD, as compared to HFD. The chromatin modifier SET and MYND Domain Containing 3 (SMYD3), whose function in adipose tissue was totally unknown, was another top-scored hit. SMYD3 expression was significantly higher in LowR HFD vWAT, as confirmed by western blot analysis. In vitro, we found that SMYD3 mRNA and protein levels decrease rapidly along the differentiation process of AD-hMSCs. Moreover, SMYD3 knock-down at the beginning of adipocyte differentiation resulted in reduced cell proliferation and, at longer term, reduced lipid accumulation in adipocytes. Conclusions Our study describes for the first time the role of SMYD3 as a regulator of adipocyte proliferation during the early steps of adipogenesis.

			Action	DRS
	QEKAC230423_08.raw	Raw
	QEKAC230423_10.raw	Raw
	QEKAC230423_12.raw	Raw
	QEKAC230423_32.raw	Raw
	QEKAC230423_34.raw	Raw

Dataset Information

Nuclear hormone-sensitive lipase controls adipocyte function

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets