Adropin deficiency worsens HFD-induced metabolic defects

Abstract

The limited efficacy of current treatment methods and increased type 2 diabetes mellitus (T2DM) incidence constitute an incentive for investigating how metabolic homeostasis is maintained, to improve treatment efficacy and identify novel treatment methods. We analyzed a three-generation family of Chinese origin with the common feature of T2DM attacks and fatty pancreas (FP), alongside 19 unrelated patients with FP and 58 cases with T2DM for genetic variations in Enho, serum adropin, and relative Treg amounts. Functional studies with adropin knockout (AdrKO) in C57BL/6J mice were also performed. It showed serum adropin levels were significantly lower in FP and T2DM patients than in healthy subjects; relative Treg amounts were also significantly decreased in FP and T2DM patients, and positively associated with adropin (r=0.7220, P=0.0001). Sequencing revealed that the patients shared a Cys56Trp mutation in Enho. In vivo, adropin-deficiency was associated with increased severity of glucose homeostasis impairment and fat metabolism disorder. AdrKO mice exhibited reduced endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177), impaired glycosphingolipid biosynthesis, adipocytes infiltrating, and loss of Treg, and developed FP and T2DM. Adropin-deficiency contributed to loss of Treg and the development of FP disease and T2DM.

Adropin as A Fat-Burning Hormone with Multiple Functions—Review of a Decade of Research

“…Downregulation of adropin in circulation in type 2 diabetes was also reported by Chen et al [24]. These patients, who also have fatty pancreases, have lower serum levels of adropin [24]. It is also important to note that patients with lower adropin levels show a Cys56Trp mutation in the Enho gene [24].…”

“…In addition, low levels of adropin in type 2 diabetes mellitus are a risk factor for endothelial dysfunction [23]. Downregulation of adropin in circulation in type 2 diabetes was also reported by Chen et al [24]. These patients, who also have fatty pancreases, have lower serum levels of adropin [24].…”

“…These patients, who also have fatty pancreases, have lower serum levels of adropin [24]. It is also important to note that patients with lower adropin levels show a Cys56Trp mutation in the Enho gene [24]. Lower levels of adropin in circulation was also reported in women with gestational diabetes [25,26].…”

A Review of Adropin as the Medium of Dialogue between Energy Regulation and Immune Regulation

“…Meanwhile, the decrease of Treg cells in adipose tissue also leads to the occurrence of insulin resistance, so it is believed that Treg cells play an important role in metabolic regulation [20,21]. Additionally, a previous research reported that adropin deficiency associates with loss of Treg cells and leads to autoimmune diseases [22].…”

“…With regulation of the phenotype of macrophages, it exerts proinflammatory or anti-inflammatory effects on atherosclerosis. In terms of energy metabolism, metabolic disorders caused by insulin resistance or inflammation leads to activations of inflammatory transcription factor nuclear factor kB (NF-κB) and inflammatory signaling system, as well as elevated levels of cytokines, thereby accelerating the damage to function of endothelial cells and formation of atherosclerotic plaques [22]. As a regulator of energy metabolism, adropin may exert its potential anti-inflammatory effects through regulation of energy metabolism.…”