Abstract
FNDC5 is the precursor of the myokine irisin proposed to exhibit favorable metabolic activity, including anti-obesity and anti-diabetes effects. The diversity of FNDC5 transcripts has been reported by several studies, but the role and existence of these transcripts are not well defined. In our previous study, a novel secretable FNDC5 (sFNDC5) isoform lacking the transmembrane region was found in rat INS-1 cells and multiple rat tissues. In the current study, we established a high-yield system for the expression and purification of sFNDC5 in Pichia pastoris, and functional investigations were undertaken using 3T3-L1 cells. We discovered that this new isoform has similar and even stronger biological functions than irisin, which may be due to its more complete structure without cleavage. Hence, we believe that sFNDC5, as the first identified readily secretable derivative, can better induce lipolysis and can potentially prevent obesity and related metabolic diseases.
Highlights
Obesity, which is associated with the development of various metabolic diseases, has been highlighted as a priority public health problem worldwide in recent decades [1, 2]
Through alignment of the amino acid sequences of this new secretable fibronectin type III domain containing 5 (FNDC5) (sFNDC5) transcript and membrane-bound FNDC5, we found that this variant lacks a transmembrane domain but shares most of the irisin sequence (Figure 1)
By measuring A280, we found that the expression of r-sFNDC5 was timedependent (Figure 2A)
Summary
Obesity, which is associated with the development of various metabolic diseases, has been highlighted as a priority public health problem worldwide in recent decades [1, 2]. The main function of WAT is to store energy, while BAT can dissipate energy as heat through mitochondrial uncoupled respiration [5, 6]. Beige adipocytes have been described as a third type of adipose cell, which can be transformed from white adipocytes and have a thermogenic function [7–10]. These inducible beige adipocytes share several biochemical features with BAT, such as the ability to dissipate energy through the uncoupling protein 1 (UCP-1)-mediated uncoupling of oxidative phosphorylation to maintain body temperature [11, 12]
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