Abstract
Heat shock protein 60 (HSP60) is a key protein in the crosstalk between cellular stress and inflammation. However, the status of HSP60 in diabetes and obesity is unclear. In the present study, we investigated the hypothesis that HSP60 expression levels in the adipose tissue of human obese adults with and without diabetes are different and physical exercise might affect these levels. Subcutaneous adipose tissue (SAT) and blood samples were collected from obese adults with and without diabetes (n = 138 and n = 92, respectively, at baseline; n = 43 for both groups after 3 months of physical exercise). Conventional RT-PCR, immunohistochemistry, immunofluorescence, and ELISA were used to assess the expression and secretion of HSP60. Compared with obese adults without diabetes, HSP60 mRNA and protein levels were decreased in SAT in diabetic obese together with increased inflammatory marker expression and glycemic levels but lower VO2 Max. More interestingly, a 3-month physical exercise differentially affected HSP60 expression and the heat shock response but attenuated inflammation in both groups, as reflected by decreased endogenous levels of IL-6 and TNF-α. Indeed, HSP60 expression levels in SAT were significantly increased by exercise in the diabetes group, whereas they were decreased in the non-diabetes group. These results were further confirmed using immunofluorescence microscopy and anti-HSP60 antibody in SAT. Exercise had only marginal effects on HSP60 secretion and HSP60 autoantibody levels in plasma in both obese with and without diabetes. Physical exercise differentially alleviates cellular stress in obese adults with and without diabetes despite concomitant attenuation of the inflammatory response.
Highlights
Obesity and type 2 diabetes (T2D) are global public health problems affecting both people’s quality of life and socioeconomics around the globe [1]
There were no significant differences between the two groups regarding gender, age, waist or hip circumference, BMI, percent body fat (PBF), and blood pressure
Fasting blood glucose (FBG), Hemoglobin A1c (HbA1c), and HOMA-insulin resistance (IR) values were significantly higher in the diabetes group, there was no difference between the two groups regarding serum insulin or C-peptide concentrations in the blood
Summary
Obesity and type 2 diabetes (T2D) are global public health problems affecting both people’s quality of life and socioeconomics around the globe [1] The pathophysiology of these metabolic diseases is closely linked, with the resulting insulin resistance (IR) as the cause of several health comorbidities [2]. We recently observed increased expression of major HSPs, including HSP72, in both adipose tissue and blood cells from obese people without diabetes [12]. This finding suggests that in this population the HSR can resolve metabolic stresses attributable to obesity, highlighting differences in molecular pathophysiology between obese subjects with and without diabetes even though both conditions are associated with IR
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