2. Academic Validation
  3. Reduction of specific enterocytes from loss of intestinal LGR4 improves lipid metabolism in mice

Reduction of specific enterocytes from loss of intestinal LGR4 improves lipid metabolism in mice

  • Nat Commun. 2024 May 23;15(1):4393. doi: 10.1038/s41467-024-48622-5.
Yuan Liang # 1,  Chao Luo # 1,  Lijun Sun 1,  Tiange Feng 1,  Wenzhen Yin 1,  Yunhua Zhang 1,  Michael W Mulholland 2,  Weizhen Zhang 3 4,  Yue Yin 5
Affiliations

Affiliations

  • 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, and State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, 100191, Beijing, China.
  • 2 Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109-0346, USA.
  • 3 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, and State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, 100191, Beijing, China. weizhenzhang@bjmu.edu.cn.
  • 4 Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109-0346, USA. weizhenzhang@bjmu.edu.cn.
  • 5 Department of Pharmacology, School of Basic Medical Sciences, and State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, 100191, Beijing, China. yueyin@bjmu.edu.cn.
  • # Contributed equally.
PMID: 38782937 DOI: 10.1038/s41467-024-48622-5
Abstract

Whether intestinal Leucine-rich repeat containing G-protein-coupled receptor 4 (LGR4) impacts nutrition absorption and energy homeostasis remains unknown. Here, we report that deficiency of Lgr4 (Lgr4iKO) in intestinal epithelium decreased the proportion of enterocytes selective for long-chain fatty acid absorption, leading to reduction in lipid absorption and subsequent improvement in lipid and glucose metabolism. Single-cell RNA Sequencing demonstrates the heterogeneity of absorptive enterocytes, with a decrease in enterocytes selective for long-chain fatty acid-absorption and an increase in enterocytes selective for carbohydrate absorption in Lgr4iKO mice. Activation of Notch signaling and concurrent inhibition of Wnt signaling are observed in the transgenes. Associated with these alterations is the substantial reduction in lipid absorption. Decrement in lipid absorption renders Lgr4iKO mice resistant to high fat diet-induced obesity relevant to wild type littermates. Our study thus suggests that targeting intestinal LGR4 is a potential strategy for the intervention of obesity and liver steatosis.

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