Abstract
Heat shock response is an essential cellular stress response. Dysregulation of various heat shock proteins (HSPs), within the heat shock response (HSR) pathway, play a vital role in this host-defense mechanism contributing to obesity-induced insulin resistance and type 2 diabetes (T2D). Previously, we have reported changes in the expression levels of several HSPs such as HSP40, HSP60, HSP70, and HSP90 in obese compared with lean individuals. DNAJC27 is a member of the HSP40 protein family that was previously identified as a body mass index (BMI) associated locus in genome-wide association (GWAS) studies. However, not much is known about the changes in DNAJC27 expression levels in obesity and T2D. In the present study, we aimed at understanding changes in DNAJC27 expression levels in plasma, peripheral blood mononuclear cells (PBMCs) and adipose tissue in association with obesity and T2D. A total of 277 individuals enrolled including 160 non-diabetic (96 non-obese and 64 obese) and 117 T2D (45 non-obese and 72 obese) individuals. Plasma level of DNAJC27 was significantly higher in obese individuals (6.28 ± 0.64 ng/mL) compared with non-obese individuals (4.8 ± 0.45 ng/mL) with P = 0.043. Dividing the population based on diabetes status showed that there was a significant increase in the plasma level of DNAJC27 in obese (6.90 ± 1.3 ng/mL) compared with non-obese individuals (3.81 ± 0.43 ng/mL) (P = 0.033) in the non-diabetic group. Similarly, DNAJC27 expression level was also higher in PBMCs and adipose tissue of obese individuals. DNAJC27 was found to be associated with leptin and resistin, adipokines known to be dysregulated in obesity, that stimulate inflammatory processes leading to metabolic disorders. In conclusion, our data show that DNAJC27 is elevated in obese and T2D individuals and was positively associated with obesity biomarkers such as leptin and resistin suggesting that this protein may play a role in the pathophysiology of these disorders.
Highlights
Obesity is a global epidemic that is associated with numerous comorbidities such as type 2 diabetes (T2D) and cardiovascular disease [1]
We have studied DNAJB3, another heat shock protein (HSP) that belongs to the HSP40 protein family and observed it to be downregulated in obese individuals and restored following physical exercise [14]
After classifying the population based on diabetes, within the non-diabetic population, a significantly higher Fasting blood glucose (FBG), and TGL (P < 0.05) was seen in the obese individuals when compared to non-obese individuals (Table 2)
Summary
Obesity is a global epidemic that is associated with numerous comorbidities such as T2D and cardiovascular disease [1]. Chronic low-grade inflammation and altered stress response are associated with obesity and play a key role in the pathology of insulin resistance and T2D [2,3,4,5]. Hotamisligil et al identified TNF-α as the first molecular link between obesity and inflammation [6]. This inflammatory cytokine was observed to be over-expressed in the adipose tissue and in the muscles of animal models of obesity and in humans [7,8,9]. Understanding the molecular mechanisms involved in chronic low-grade inflammation is essential for developing strategies to mitigate obesity and disorders associated with it
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