Lmo4-resistin signaling contributes to adipose tissue-liver crosstalk upon weight cycling

Yu Sun, Mengyuan Geng, Yangmian Yuan, Peilian Guo, Yuchen Chen, Dong Yang, Robert B. Petersen, Kun Huang, Ling Zheng

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Repeated cycles of weight loss and regain, known as weight cycling, is often seen when people try to lose weight. The exact pathophysiological effects and the underlying mechanisms of weight cycling remain largely unclear. Here, we report that weight cycling induced by alternating feeding mice with a low-fat diet or a high-fat diet in a 1-week switch protocol caused further increased epididymal white adipose tissue (eWAT) weight, preadipocyte proliferation, hepatic inflammation, fasting blood glucose level, and glucose intolerance, compared with the continuously HF-fed mice. Combining the secretory protein database with RNA-sequencing and quantitative PCR (qPCR) results in eWAT, the mRNA levels of several adipokines, including Retn (encoding resistin), were found altered by weight cycling. A transcriptional co-factor Lmo4 was found regulated by weight cycling; Lmo4 enhanced preadipocyte proliferation, in vitro adipogenesis, transcription of Retn, and resistin secretion in 3T3-L1 cells. Primary mouse hepatocytes administrated with recombinant mouse resistin (rm-resistin), or exposed to media from Lmo4-overexpressed 3T3-L1 cells, showed increased inflammatory responses and gluconeogenesis. Furthermore, rm-resistin-injected normal chow-fed mice showed upregulated blood glucose level by increasing gluconeogenesis, and upregulated the hepatic inflammatory responses. Together, our results suggest a regulatory role of Lmo4-resistin signaling in weight cycling, indicating a crosstalk between the adipose tissue and liver.

Original languageEnglish
Pages (from-to)4732-4748
Number of pages17
JournalFASEB Journal
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2020

Keywords

  • Lmo4
  • adipose tissue-liver crosstalk
  • diet-induced weight cycling
  • hepatic inflammation
  • resistin

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