# The Asp-Encoding Gene FBN1 Mediates Cold Adaptation in Sunite Sheep by Reprogramming Adipocyte Differentiation Towards Thermogenesis

## TL;DR

Sunite sheep adapt to cold by reducing the FBN1 gene, which changes fat cells to generate more heat.

## Contribution

The study identifies FBN1 as a key gene in cold adaptation through adipocyte reprogramming in Sunite sheep.

## Key findings

- Downregulation of FBN1 in adipose tissue during winter reduces lipid synthesis and promotes thermogenesis.
- FBN1 inhibition in adipocytes impairs adipogenesis and enhances browning of white adipose tissue.
- Reduced FBN1 levels increase thermogenic markers like UCP1 and NEFA in differentiated adipocytes.

## Abstract

What are the main findings?
The precursor protein of asprosin (pFBN1) was significantly downregulated in the adipose tissue of Sunite sheep during winter.Inhibition of the FBN1 gene in adipocytes not only impeded adipogenesis but also promoted the browning of white adipose tissue, enhancing thermogenesis.

The precursor protein of asprosin (pFBN1) was significantly downregulated in the adipose tissue of Sunite sheep during winter.

Inhibition of the FBN1 gene in adipocytes not only impeded adipogenesis but also promoted the browning of white adipose tissue, enhancing thermogenesis.

What are the implications of the main findings?
This study provides novel molecular targets for the selective breeding of sheep with improved cold tolerance.The findings offer fresh insights into the regulatory mechanisms of mammalian energy metabolism and adipose tissue adaptation.

This study provides novel molecular targets for the selective breeding of sheep with improved cold tolerance.

The findings offer fresh insights into the regulatory mechanisms of mammalian energy metabolism and adipose tissue adaptation.

Sunite sheep are well-adapted to the cold Mongolian steppe, exhibiting robust metabolic flexibility in which adipose tissue contributes significantly to energy homeostasis. Proteomics analysis of scapular fat in Sunite sheep during winter and summer identified 432 upregulated and 493 downregulated differentially expressed proteins (DEPs). These DEPs were notably enriched in essential biological functions such as energy metabolism, lipogenesis, and thermogenesis. Furthermore, they exhibited significant enrichment of signaling pathways such as oxidative phosphorylation and fatty acid metabolism. Meanwhile, the precursor protein of asprosin (ASP),profibrillin-1 (pFBN1), showed a marked decrease during winter. Given that ASP had been demonstrated to exert metabolic regulatory effects promoting lipid synthesis and suppressing thermogenesis in model animals, it was hypothesized that the seasonal downregulation of pFBN1 might drive adaptive thermogenesis through ASP. Therefore, this study focused on functional validation of the ASP-encoding gene FBN1 (fibrillin-1). In Adipose-Derived Mesenchymal Stem Cells (ADMSCs), FBN1 was specifically downregulated through overexpressing of its regulatory factor miR-29b-1. The results indicated that downregulation of the FBN1 led to the inhibition of adipogenesis in ADMSCs. This was reflected by a reduction in the number of lipid droplets, a decrease in the expression of adipogenesis marker genes, and a significant drop in triglyceride levels. Furthermore, the reduction in FBN1 levels enhanced the thermogenic function of differentiated adipocytes derived from ADMSCs, as evidenced by enhanced expression of thermogenic marker genes, along with a notable rise in both uncoupling protein 1 (UCP1) and non-esterified fatty acid (NEFA) levels.