Dataset Information

Adipocyte ILF3 Deficiency Improves Diet-induced Obesity and Metabolic Disorders through PUFA Synthesis

ABSTRACT: A moderate long-chain polyunsaturated fatty acids (LC-PUFAs) intake may improve obesity and metabolic disorders. However, regulating endogenous LC-PUFAs and their function is unclear. Here, adipocyte ILF3 expression promotes high-fat diet (HFD)–induced obesity and metabolic disorders by inhibiting endogenous omega-3 LC-PUFAs (n-3-LC-PUFA) biosynthesis. In patients with obesity, serum ILF3 levels are elevated and positively correlate with high triglyceride levels. The expression of ILF3 in adipose tissue from patients with obesity and HFD-induced obese mouse models is positively correlated with adipocyte size. Adipose tissue ILF3 expression in patients with obesity and HFD–induced obese mice positively correlates with adipocyte size. Adipocyte ILF3 deficiency significantly increases white adipose tissue browning, promotes brown adipose tissue thermogenesis, and improves HFD–induced obesity and metabolic disorders. ILF3 recruits DNMT1, which reduces FADS2 transcription and inhibits n-3-LC-PUFA biosynthesis. Similarly, sc26196, a FADS2-specific inhibitor, exacerbates obesity and metabolic disorders. Fenofibrate, an anti-triglyceride drug, improves obesity and metabolic disorders by inhibiting ILF3 expression and increasing endogenous n-3-LC-PUFA biosynthesis. Collectively, inhibiting adipocyte ILF3 expression may be an effective alternative treatment for these conditions.

ORGANISM(S): Mus musculus

PROVIDER: GSE338031 | GEO | 2026/07/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

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.

Dataset Information

Adipocyte ILF3 Deficiency Improves Diet-induced Obesity and Metabolic Disorders through PUFA Synthesis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets