Other
14 Authors
- Su V,
- Sallam T,
- Tontonoz P,
- Kim J,
- Li W,
- Tol MJ,
- Rajbhandari P,
- Villanueva CJ,
- Cheng L,
- Zhang Z,
- Wang D,
- Cui Y,
- Wu X,
- Zhang S
| First Author | Zhang Z | Year | 2023 |
| Journal | J Clin Invest | Volume | 133 |
| Issue | 21 | PubMed ID | 37909330 |
| Mgi Jnum | J:355346 | Mgi Id | MGI:7546741 |
| Doi | 10.1172/JCI170072 | Citation | Zhang Z, et al. (2023) A PPARgamma/long noncoding RNA axis regulates adipose thermoneutral remodeling in mice. J Clin Invest 133(21) |
| abstractText | Interplay between energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of specialized niche, adipocytes require the activity of the nuclear receptor PPARgamma for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARgamma; however, the molecular mechanisms by which PPARgamma licenses white adipose tissue to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARgamma/long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity. Pharmacologic inhibition or genetic deletion of the lncRNA Lexis enhances uncoupling protein 1-dependent (UCP1-dependent) and -independent thermogenesis. Adipose-specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARgamma and WNT that preserves white adipose tissue plasticity. |
